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PubMed2026

Tumour-infiltrating lymphocytes differ across MammaPrint® classifications in breast cancer.

MammaPrint® refines risk stratification in early oestrogen receptor-positive, HER2-negative breast cancer, evolving from a binary to a four-tier classification (UltraLow-Risk, Low-Risk, High-Risk 1, and High-Risk 2). The relationship between routine histopathological features, immune infiltration, and genomic risk within this framework remains incompletely characterized in luminal disease. We retrospectively analysed 492 luminal breast carcinomas with available MammaPrint® results. Clinicopathological variables (including histological subtype, grade, Ki-67, hormone receptor expression, lymphovascular invasion (LVI), and HER2-low status) were recorded. Stromal tumour-infiltrating lymphocytes (TILs) were quantified according to the criteria of Salgado et al. and spatially categorized as immune-deserted, stromal-restricted, immune-excluded, or inflamed patterns. CD4 and CD8 infiltration was assessed by immunohistochemistry on tissue microarrays. Associations with binary and four-tier MammaPrint® categories were examined using multivariable models. High-Risk tumours (41%) were enriched for increased grade, Ki-67, and LVI and lower PR expression. In High-Risk tumours, inflamed spatial patterns were more frequent and median TIL levels were significantly higher compared with Low-Risk tumours (15% vs 5%, P < 0.001). CD4 and CD8 infiltration increased with genomic risk, and CD4 retained a modest but statistically significant association after adjustment for conventional pathological variables. In the four-tier model, UltraLow-Risk/Low-Risk tumours showed minimal TILs and were enriched for invasive lobular carcinoma, whereas High-Risk 1/High-Risk 2 tumours displayed progressively higher proliferative and immune features. No association was observed between HER2-low status and genomic risk. Immune infiltration parallels proliferative and genomic risk gradients in luminal breast cancer. These findings indicate that immune descriptors align with the genomic risk continuum, although their independent prognostic contribution beyond established genomic assays requires further evaluation.

Humans↗

PubMed2018

Thioredoxin interacting protein promotes invasion in hepatocellular carcinoma.

BACKGROUND: Considerable evidence suggests that oxidative stress plays an essential role in the progression of hepatocellular carcinoma (HCC). While acquired resistance to oxidative stress is the main driver of aggressive cell phenotype, the underlying mechanisms remain unknown. Here, we tested the hypothesis that elevated expression of Thioredoxin-interacting protein (TXNIP) is a main regulator of the aggressive phenotype in HCC. MATERIALS AND METHODS: To test this hypothesis, we measured TXNIP expression levels in 11 HCC cell lines by qPCR and western blotting. In addition, 80 pairs of HCC tissues and matched liver tissues of 73 cases, as well as 11 normal liver tissue samples were examined by immunohistochemistry. Besides, TXNIP expression levels were analyzed by Oncomine Platform in seven independent microarray datasets. Finally, the functional role of TXNIP in HCC was investigated in vitro and in vivo by silencing and overexpression studies. RESULTS: Our results show that TXNIP expression is significantly increased in HCC compared to non-tumor counterparts (p < 0.0001) as well as to normal (p < 0.0001) and cirrhotic (p < 0.0001) liver tissues. Moreover, stable overexpression of TXNIP in HCC cells (i) significantly increases ROS levels, (ii) induces EMT phenotype, (iii) increases motility, invasion and 3D branching tubulogenesis, (iv) decreases apoptosis, and (v) elevates in vivo metastasis in zebrafish embryos. Finally, we identify sinusoidal/stromal and cytoplasmic TXNIP staining patterns as risk factors for intrahepatic vascular invasion (p:0.0400). CONCLUSION: Our results strongly suggest that overexpression of TXNIP has a pivotal role in HCC progression by inducing cell survival, invasion, and metastasis.

EMT↗

PubMed2025

Effect of Chang'an decoction on ulcerative colitis by regulating T helper 17 cells and regulatory T cellsRab27 in the p53/high mobility group box 1 pathway.

OBJECTIVE: To explore the effect of Chang'an decoction (, CAD) of ameliorating the immune imbalances in ulcerative colitis (UC) by regulating Rab27 in the P53/high mobility group box 1 pathway. METHODS: The functions and important signaling pathways of the Rab27- and UC-related genes were analyzed viathe use of microarray data from the gene expression omnibus database, gene ontology database, Kyoto encyclopedia of genes and genomes database and gene set enrichment analysis. Dextran sulfate sodium salt-induced colitis mouse model was used to verify the bioinformatics results. Colon length, body weight, and disease activity index were measured. Hematoxylin and eosin staining was applied to validate the histopathology. Tight junction proteins were detected by immunohistochemistry. The proportions of T helper 17 cells (Th17) and regulatory T cells (Treg) in mesenteric lymph nodes were measured viaflow cytometry. Proinflammatory cytokines like interleukin (IL) 17 (IL-17), IL-21 and IL-22 and anti-inflammatory cytokines like transforming growth factor β and IL-10 in the serum and colon of mice were detected by enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction, respectively. The expression levels of high mobility group box 1 (HMGB1), P53 and phospho- P53 (P-P53) in colonic tissues were detected by immunofluorescence and Western blotting. RESULTS: Bioinformatics analysis revealed that compared with normal tissues, the expression of Rab27 was significantly increased in UC tissues. Receiver operating characteristic curve showed that Rab27 has the potential to be used as a biomarker for the diagnosis of disease activity. Enrichment analysis showed that UC and Rab27 were mainly associated with small molecule transport, nutrient metabolism, transmembrane transport and the downstream pathway of P53. According to animal experiments, the expression of Rab27 was increased in UC tissues, which aggravated the colonic pathological damage, activated the expression of HMGB1, and also leaded to the imbalance of Th17 and Treg cells. After CAD intervention, Rab27 overexpression, weight loss, colon shortening, and pathological damage were substantial reduced, the expression of tight junction proteins, zona occludens 1 and Occludin were increased. The effect of CAD at high-dose was more obvious. In addition, CAD upgraded the number of Treg cells and the production of TGF-β and IL-10, while decreasing the number of Th17 cells and the expression of inflammatory cytokines (IL-17, IL-21, and IL-22). Moreover, colon inflammation was alleviated by CAD, as indicated by the regulation of HMGB1 and P-P53 expression. CONCLUSION: The expression of Rab27, HMGB1 and P-P53 could be decreased by CAD, and the balance of Th17 and Treg cells as well as their related cytokines could be regulated by CAD.

Animals↗

PubMed2026

Development and Validation of a Prognostic Signature Based on Transcription Factors Associated with Endoplasmic Reticulum Stress in Pancreatic Adenocarcinoma.

BACKGROUND: Endoplasmic reticulum stress (ER stress) plays a crucial role in influencing the malignant behaviors of various tumors. Targeting the expression or degradation of transcription factors (TFs) offers a promising avenue for cancer treatment. However, a detailed understanding of how ER stress affects TF function and their interactions remains limited. This study aims to develop a prognostic model and identify TFs associated with ER stress in pancreatic ductal adenocarcinoma (PDAC). METHODS: We obtained gene expression profiles and corresponding clinical data from The Cancer Genome Atlas (TCGA). To develop a prognostic signature, we performed several analyses, including unsupervised clustering, enrichment analysis, immune infiltration assessment, as well as univariate, LASSO, and multivariate Cox regression analyses. Four transcription factors-STAT1, IRF6, NRF1, and RXRA-were incorporated into a risk model, which was subsequently validated using the GSE dataset. Additionally, we examined IRF6 through quantitative PCR, western blotting, flow cytometry, and immunohistochemistry in vitro using pancreatic cancer cell lines and a tissue microarray. RESULTS: The high-risk group identified by the model exhibited significant associations with immune cell infiltration and poorer survival outcomes, though there was no significant correlation with tumor purity (p = 0.19). Furthermore, IRF6 downregulation in vitro was found to inhibit pancreatic cancer cell proliferation and promote apoptosis. IRF6 depletion also increased the expression of key molecules involved in ER stress at both the transcriptional and translational levels. Immunohistochemical analysis revealed marked differences in IRF6 expression between tumor and adjacent non-tumor tissues (59.29±29.88 vs. 95.22±40.80, p<0.001). CONCLUSION: This study provides evidence that the constructed risk model can effectively predict prognosis in PDAC patients. Transcription factors related to ER stress, such as IRF6, show promise as both prognostic biomarkers and potential therapeutic targets for PDAC.

Humans↗

PubMed2026

CTGF/CCN2 Promotes Invasive Growth in Cervical Cancer Spheroids and Is Associated With Metastatic Cervical Cancer Tissue.

BACKGROUND/AIM: Metastatic spread defines the lethality of cervical cancer (CC). Connective tissue growth factor (CTGF/CCN2) regulates cell- extracellular matrix interactions but its role in CC is not well-defined. This study investigates the role of CTGF in driving CC invasive growth and its prevalence in patient tissues. MATERIALS AND METHODS: CC spheroids (C33A, HT3) were treated with recombinant human CTGF (rhCTGF) or a function-blocking antibody (IgG CTGF). Invasive growth was assessed via 3D spheroid assay using a Celigo imaging cytometer. Cancer stem cell (CD133, CD44) and epithelial-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin) were analyzed by immunofluorescence. CTGF expression was evaluated using a tissue microarray containing 69 cases in triplicate from pre-invasive, invasive (FIGO I-III), and metastatic cervical lesions, quantified via immunofluorescence scoring. RESULTS: Functional blockade of CTGF significantly reduced 3D spheroid invasive growth in C33A and HT3 cells (p<0.0001). Immunofluorescence revealed that CTGF modulation altered spatial distribution of key proteins: rhCTGF induced surface clustering of CD133 and peripheral N-cadherin enrichment, while CTGF blockade was associated with apparent nuclear/perinuclear enrichment of CD133 and E-cadherin and reduced N-cadherin signal. In patient tissue cores, metastatic samples exhibited the highest CTGF fluorescence intensity. High CTGF expression [immunoreactivity score (IRS) ≥ 6] was most prevalent in FIGO stage I (35.5%) compared to stage III (10.0%). Kaplan-Meier analysis revealed that high CTGF mRNA expression was associated with significantly reduced recurrence-free survival (log-rank p=0.0032). CONCLUSION: In 3D models of CC, CTGF appears to regulate an invasive phenotype, presumably by controlling aberrant localization of stemness and EMT markers. Its apparently elevated expression in early-stage cervical carcinomas and metastases, combined with its prognostic value for recurrence-free survival, suggests that CTGF may be involved in triggering the potential for metastasis and could therefore serve as an early prognostic biomarker.

Humans↗

PubMed2026

AI-Supported, Integrative Prediction of Postoperative Delirium: Protocol for the CONFUSED Study.

BACKGROUND: Postoperative delirium (POD) is a frequent and serious complication in older surgical patients, characterized by acute cognitive dysfunction and fluctuating levels of consciousness. POD is associated with prolonged hospitalization, long-term cognitive decline, reduced quality of life, and increased mortality. Despite its clinical relevance, the underlying pathophysiological mechanisms remain poorly understood, and reliable biomarkers for early prediction and prevention are lacking. OBJECTIVE: The CONFUSED study aims to identify molecular and clinical predictors of POD by integrating clinical data with proteomic, transcriptomic, and epigenetic analyses. The primary objective is to develop predictive models for POD using multimodal data. Secondary objectives include the identification of delirium-associated genes, proteins, and epigenetic signatures, as well as the exploration of patient subgroups at increased risk for POD. METHODS: CONFUSED is a prospective observational cohort study conducted at a German university hospital. Adult patients undergoing major surgery under general anesthesia will be enrolled until 100 cases of POD have been observed, which is expected to require a total sample size of approximately 200 to 300 patients. Blood samples are collected at 4 predefined time points: before premedication, immediately after surgery, and on postoperative days 2 and 5. Samples undergo comprehensive proteomic profiling, transcriptomic analysis using RNA microarrays, DNA methylation analysis, and genotyping of selected polymorphisms. Clinical data, including demographics, comorbidities, perioperative variables, medications, and delirium assessments using the Confusion Assessment Method (CAM) and CAM for the intensive care unit, are systematically recorded. Statistical analyses include univariate and multivariate methods, as well as machine learning approaches such as random forests and support vector machines, to identify relevant biomarkers and develop predictive models. The study protocol follows STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) and TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) guidelines and was approved by the responsible ethics committees. RESULTS: The study was registered in the German Clinical Trials Register (DRKS00033854) on March 18, 2024. Recruitment started in January 2024 and is ongoing at the time of manuscript submission. As of now, 135 patients have been enrolled. Sample collection and laboratory analyses are ongoing. Data analysis began in January 2026, with first results anticipated in July 2026. Final data lock is anticipated after the completion of recruitment. CONCLUSIONS: By integrating multimodal molecular data with clinical parameters and applying advanced machine learning techniques, the CONFUSED study aims to improve the prediction and understanding of POD. The results are expected to support the development of personalized preventive strategies and contribute to improved perioperative care for patients at risk of POD.

Humans↗

PubMed2025

Genomic mapping of diabetic kidney disease biomarkers and identification of potential inhibitors through virtual screening.

BACKGROUND: Diabetic kidney disease (DKD) is a common and serious complication of diabetes mellitus, marked by a multifactorial pathogenesis and the absence of sensitive diagnostic biomarkers. Identifying novel molecular targets and therapeutic options is essential to improve early diagnosis and treatment outcomes. METHODS: To uncover potential biomarkers and therapeutic candidates, we performed an integrated genomic analysis using microarray and RNA-seq datasets from the Gene Expression Omnibus (GEO) and Sequence Read Archive (SRA) databases. Differentially expressed genes (DEGs) were identified and subjected to protein-protein interaction (PPI) network analysis. Key genes were further explored through virtual screening of an FDA-approved compound library using molecular docking techniques. Drug-likeness was assessed via Lipinski's rule of five. RESULTS: A total of 40 DEGs were identified, among which ISCU (downregulated; involved in iron-sulfur cluster biogenesis) and AP1S2 (upregulated; associated with vesicular trafficking) emerged as potential biomarkers. PPI analysis revealed their involvement in critical DKD-related pathways, such as extracellular matrix remodeling and oxidative stress. Virtual screening identified six FDA-approved compounds with high binding affinity (≤-7.96 kcal/mol) to ISCU, notably ZINC000001576020, all of which complied with Lipinski's rule. CONCLUSIONS: This in-silico study nominates ISCU and AP1S2 as candidate diagnostic biomarkers for DKD and identifies computationally prioritized inhibitors targeting ISCU. These findings require experimental validation but provide a molecular framework for precision diagnosis and therapeutic development. These findings offer new molecular insights that could inform precision diagnosis and personalized treatment strategies for diabetic kidney disease.

Diabetic Nephropathies↗

PubMed2026

Human periodontal ligament stem cells promote oral ulcer healing in rats through modulation of TGF-β1/smad signaling.

BACKGROUND: Oral ulcers (OU) often present with prolonged healing, recurrent episodes, and scar formation, posing challenges for clinical management. Human periodontal ligament stem cells (hPDLSCs) have shown potential in oral tissue repair, but further research is needed to clarify their mechanism of action in OU healing. This study aims to elucidate the molecular mechanisms by which hPDLSCs promote oral ulcer healing. METHOD: To identify key regulatory genes, the OU-associated microarray dataset GSE37265 was integrated with hPDLSC genomic data for differential expression analysis. Subsequently, Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify functional modules associated with OU healing. In vivo, hPDLSCs were locally administered into a rat ulcer model, and therapeutic efficacy was assessed by ulcer closure rates and histological evaluation (HE and Masson's trichrome staining). Furthermore, RNA-sequencing (RNA-seq) was performed on oral mucosal tissues to delineate the underlying molecular landscape and critical signaling pathways. The involvement of the TGF-β signaling pathway was confirmed by real-time quantitative PCR (RT-qPCR) and Western blotting (WB) analyses. RESULTS: Bioinformatics analysis identified 92 key genes in hPDLSCs-mediated treatment of OU, highlighting the central role of the TGF-β1/Smad pathway. As shown by the animal studies, hPDLSCs therapy increased the healing rate to 97% by day 8 (vs. 70% in the model). Furthermore, the therapy significantly reduced inflammatory cell infiltration and abnormal collagen deposition while promoting regular collagen arrangement. Transcriptomic and molecular experiments further showed that hPDLSCs simultaneously inhibit TGF-β1/Smad and extracellular signal-regulated kinase (ERK) signaling pathways, thereby alleviating inflammatory responses and suppressing mucosal fibrosis. CONCLUSION: In this study, we reveal a novel role for hPDLSCs in promoting oral ulcer healing. The findings indicate that hPDLSCs suppress inflammation and fibrosis via the TGF-β1/Smad pathway, offering a promising therapeutic strategy for OU and other fibrotic conditions.

TGF-β1↗

PubMed2026

Genome-wide transcriptional landscape of Mycobacterium tuberculosis during acute lung infection.

Tuberculosis (TB) remains a major global health burden, yet the mechanisms by which Mycobacterium tuberculosis (Mtb) adapts to host environments to drive disease pathology are incompletely defined. A key limitation has been reliance on axenic culture systems that fail to recapitulate the complex, host-imposed stresses encountered by Mtb in vivo. Here, we report the first microarray-based genome-wide transcriptomic profiling of Mtb in rabbit lungs with active TB, which closely mirrors human disease features, including granuloma heterogeneity, necrosis, and cavitation. Using Mtb RNA isolated from infected lung homogenates or broth-culture, we capture bacterial transcriptional states shaped by the host microenvironments. The transcriptional data analyses reveal extensive, context-dependent reprogramming of Mtb metabolic, respiratory, and stress-response networks that diverges markedly from in vitro expression profiles, including activation of stress adaptation, lipid catabolism, nucleic acid metabolism, and transcriptional regulation pathways. These data uncover pathways and networks that are selectively engaged in vivo and likely critical for Mtb survival within granulomatous lesions. Our findings demonstrate that transcriptional states most relevant to TB pathogenesis are underrepresented in standard lab-grown Mtb models and highlight the importance of in vivo bacterial profiling. By characterizing Mtb gene expression within diseased lungs, this study provides a systems-level framework for understanding TB pathogenesis and reveals in vivo-essential pathways, offering potential targets for translational drug discovery and the development of more effective anti-TB therapies.

Animals↗

PubMed2025

Biomarker-Based Nomogram to Predict Neoadjuvant Chemotherapy Response in Muscle-Invasive Bladder Cancer.

Background/Objectives: The aim of this study was to identify response prediction and prognostic biomarkers in muscle-invasive bladder cancer (MIBC) patients undergoing neoadjuvant chemotherapy (NAC). Methods: A retrospective multicentre study including 191 patients with MIBC who received NAC previous to radical cystectomy (RC) between 1996 and 2013. Gene expression patterns were analysed in 34 samples from transurethral resection of the bladder (TURB) using Illumina microarrays. The expression levels of 45 selected differentially expressed genes between responders and non-responders to NAC were validated by quantitative PCR in an independent cohort of 157 patients. Regression analysis was used to identify predictors of downstaging and relapse. A nomogram for predicting downstaging and relapse-including clinicopathological and gene expression variables-was developed. Results: The expression levels of 1352 transcripts differed between responders and non-responders to NAC. A nomogram based on the most predictive clinical variables (age, Tis (in situ), gender, history of NMIBC, and lymphadenopathy) and genes selected following the Akaike information criterion (AIC) (CBTB16, CHMP6, DDX54, CASP8, LOR, and PLEC) was then created. In addition, a three-gene expression prognostic model to predict tumour relapse was generated. This model was able to discriminate between two groups of patients with a significantly different probability of tumour relapse (HR: 2.11; CI: 1.16-3.83, p = 0.01). Conclusions: Our nomogram based on gene expression and clinical data is a useful tool to predict downstaging and tumour relapse after NAC in MIBC patients. Further validation is warranted.

bladder cancer↗

PubMed2022

Phenotypic Impact of Rare Potentially Damaging Copy Number Variation in Obsessive-Compulsive Disorder and Chronic Tic Disorders.

BACKGROUND: Recent studies report an important-and previously underestimated-role of rare variation in risk of obsessive-compulsive disorder (OCD) and chronic tic disorders (CTD). Using data from a large epidemiological study, we evaluate the distribution of potentially damaging copy number variation (pdCNV) in OCD and CTD, examining associations between pdCNV and the phenotypes of probands, including a consideration of early- vs. late-diagnoses. METHOD: The Obsessive-Compulsive Inventory-Revised (OCI-R) questionnaire was used to ascertain psychometric profiles of OCD probands. CNV were identified genome-wide using chromosomal microarray data. RESULTS: For 993 OCD cases, 86 (9%) were identified as pdCNV carriers. The most frequent pdCNV found was at the 16p13.11 region. There was no significant association between pdCNV and the OCI-R total score. However, pdCNV was associated with Obsessing and Checking subscores. There was no significant difference in pdCNV frequency between early- vs. late-diagnosed OCD probands. Of the 217 CTD cases, 18 (8%) were identified as pdCNV carriers. CTD probands with pdCNV were significantly more likely to have co-occurring autism spectrum disorder (ASD). CONCLUSIONS: pdCNV represents part of the risk architecture for OCD and CTD. If replicated, our findings suggest pdCNV impact some OCD symptoms. Genes within the 16p13.11 region are potential OCD risk genes.

Humans↗

PubMed2026

Ocular Nystagmus as the Initial Presenting Feature in a Patient with Complete CLTC Deletion: Expanding the Genotype-Phenotype Spectrum of CLTC-Related Disorder.

Background: CLTC-related neurodevelopmental disorder is a rare condition primarily characterized by global developmental delay (GDD) and intellectual disability (ID). To date, approximately 41 cases involving CLTC gene alterations have been reported. We present the first individual with a complete deletion of the CLTC gene. Methods: The proband is a male from a non-consanguineous family, presenting with congenital nystagmus, hypotonia, GDD, and autism spectrum disorder (ASD). Chromosomal microarray analysis and trio exome sequencing were performed. A systematic review of previously reported CLTC variant cases was conducted to delineate the phenotypic spectrum. Results: A de novo 363-kb heterozygous deletion at 17q23.1 spanning the entire CLTC gene was identified. The systematic review confirmed GDD/ID as core features and revealed various ocular abnormalities in a subset of cases. These findings indicate that the clinical phenotype extends beyond neurodevelopment, with multi-system involvement. Conclusions: The phenotypic heterogeneity of CLTC-related disorders underscores the need for comprehensive physical examination to identify extra-neurological manifestations. Accurate diagnosis relies on integrating detailed clinical phenotyping with comprehensive genomic testing. Early, precise diagnosis facilitates multidisciplinary management, informed genetic counseling, and the establishment of long-term surveillance protocols.

Humans↗

PubMed2026

[Aggressive B-cell lymphomas with MYC gene cluster amplification: a clinicopathological analysis of eight cases].

Objective: To investigate the clinicopathological characteristics, molecular genetics, treatments and prognosis of aggressive B-cell lymphomas (ABCL) with MYC gene cluster amplification. Methods: Eight cases of ABCL with MYC gene cluster amplification were collected, including 6 cases from the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China and 2 consultation cases from outside hospitals. The histomorphology, immunohistochemical profiles, and molecular genetic characteristics were analyzed. Clinical follow-up and literature review were also conducted. Results: Among the eight patients, six were male and two were female, with an age 71.5 (61.7, 74.2) years. All six in-house patients presented with abdominal pain at onset, without B symptoms. Most cases were classified as Ann Arbor stage Ⅲ-Ⅳ. Extranodal involvement occurred in 5 of the 6 in-house cases, primarily affecting the gastrointestinal tract (4/5). All initial bone marrow biopsies showed no evidence of lymphoma. One patient had a history of immunosuppression following renal transplantation. Two cases exhibited diffuse large B-cell lymphoma (DLBCL) morphology. The other six showed high-grade features, while three of them showed Burkitt lymphoma-like morphology. Except for one case of blastoid variant mantle cell lymphoma, the remaining six cases (6/7) displayed a germinal center B-cell phenotype. None of the in-house cases harbored bcl-2 or bcl-6 rearrangements as shown by fluorescence in situ hybridization. 11q alterations were identified in all but one consultation case, including gain/loss type in five cases and 11q gain in two. 11q telomere loss of heterozygosity by chromosomal microarray analysis was not detected in one of the two cases with 11q gain that was subject to the test. The duration of follow-up ranged from 5.9 to 55.5 months, with 5 patients alive at the end of the study. Conclusions: ABCL with MYC gene cluster amplification often presents high-grade morphology and gastrointestinal involvement, which strongly suggests the alteration of 11q. It seems to have a favorable prognosis.

Humans↗

PubMed2026

[Optical genome mapping analysis of a Chinese pedigree with a complex balanced translocation involving four chromosomes].

OBJECTIVE: To explore the genetic characteristics of a complex balanced translocation involving four non-homologous chromosomes in a Chinese pedigree using optical genomic mapping (OGM). METHODS: A woman with primary infertility and her family members who presented at the Prenatal Diagnosis Center of the Sixth Affiliated Hospital of Sun Yat-sen University in October 2021 were selected as study subjects. Comprehensive analysis and verification of chromosomal abnormalities were conducted through conventional G-band karyotyping analysis, single nucleotide polymorphism microarray (SNP array) and OGM. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: E2022210). RESULTS: G-band karyotyping analysis indicated that the proband, her father, and younger brother have all carried a complex translocation involving four chromosomes. SNP array analysis revealed a duplication of approximately 21.63 Mb in the 9p24.1-p21.1 region in the proband's younger brother, while no abnormality was detected in other family members. OGM confirmed that the complex balanced translocation has involved chromosomes 5, 8, 9, and 10. CONCLUSION: The proband has harbored a complex balanced translocation. OGM has demonstrated certain advantages in characterization of complex chromosomal structural abnormalities.

Humans↗

PubMed2026

[Pathogenicity analysis and prenatal genetic counseling for five Chinese pedigrees harboring a hemizygous c.-32C>G variant of FGF13 gene].

OBJECTIVE: To explore the pathogenicity and prenatal counseling strategies for five Chinese pedigrees harboring a hemizygous c.-32C>G (NM_001139500.2) variant of fibroblast growth factor 13 (FGF13) gene. METHODS: Five Chinese pedigrees found to carry a hemizygous c.-32C>G variant of the FGF13 gene at the Prenatal Diagnosis Center of Henan Provincial People's Hospital between January 2024 and January 2025 were selected as study subjects. The pedigrees had undergone prenatal diagnosis for a family history of genetic disorders, abnormal fetal ultrasound findings, or advanced maternal age. A retrospective analysis was carried out, wherein clinical data for all members of the pedigrees were obtained through the medical records system and outpatient visit system. Peripheral blood samples were collected from all pedigree members, and amniotic fluid samples were obtained from the probands. Following extraction of genomic DNA, prenatal diagnosis was performed using chromosomal microarray analysis (CMA) and trio whole-exome sequencing (trio-WES). Sanger sequencing was used to determine the carrier status for the candidate variant, and Mini-Mental State Examination (MMSE) was used to assess the cognitive function of hemizygous individuals carrying the FGF13 gene c.-32C>G variant. Pathogenicity of candidate variant was assessed based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2021-171). RESULTS: CMA and trio-WES revealed no pathogenic variants in all probands, whilst trio-WES and Sanger sequencing had identified 11 male individuals carrying a hemizygous c.-32C>G variant of the FGF13 gene from the five pedigrees, which included six adult males, a young boy, and four fetuses. One fetus had undergone termination of pregnancy due to hydrocephalus, one was born pre-term at 34+1 weeks of gestation owing to maternal hypertension, and other two were delivered at full term. Follow-up of the survived males revealed no phenotypic manifestations related to language or intellectual impairment. Among these, three adult males underwent the MMSE assessment, all of whom showed normal cognitive function. Search of the gnomAD database suggested the carrier frequency of FGF13 c.-32C>G variant in the East Asian population to be 0.125%, with 11 hemizygous males documented. Three male patients harboring the variant showed severe intellectual disability. Both in vitro and in vivo studies suggested that it could reduce the translation levels of FGF13 protein. Based on the ACMG guidelines, it was classified as variant of uncertain significance (BS4+PS3_Supporting). CONCLUSION: There is insufficient evidence to classify the FGF13 c.-32C>G as a pathogenic variant in clinical practice, and its presence should not be considered an indication for pregnancy termination due to major birth defects.

Adult↗

PubMed2026

Analysis of end-stage renal disease mediated by cuproptosis-related genes.

OBJECTIVE: The complex pathophysiological mechanism of end-stage renal disease (ESRD) has not been fully understood. Cuproptosis is a newly discovered type of programmed cell death. Therefore, this study attempts to clarify the relationship between cuproptosis-related genes (CRGs) and the phenotype of ESRD. MATERIALS AND METHODS: The National Center for Biological Information Gene Expression Omnibus database was applied to obtain the GSE37171 dataset comprising whole-genome microarray analysis of peripheral blood samples. A 3 : 1 case-control design was employed with 75 ESRD patients and 20 healthy controls who were frequency-matched for age, sex, and ethnicity. Based on differentially expressed genes (DEGs) and genes related to cuproptosis, CRGs were identified. Thereafter, we explored two different subpopulations based on the cuproptosis gene and analyzed their expression and immune infiltration. Genes specific to the CRG cluster were identified through the weighted gene co-expression network analysis algorithm, and the best prediction model was determined and verified by four machine learning methods. RESULTS: The study identified 14 differentially expressed CRGs, among which ATP7B, SLC31A1, LIAS, LIPT1, DLD, MTF1, CDKN2A, DBT, and DLST had relatively high expression levels in the ESRD samples. Compared with the control group, expression levels of FDX1, DLAT, PDHA1, PDHB, and GLS were significantly lower in the ESRD group, and CRGs played a key role in the regulation of immune infiltration in ESRD. Two cuproptosis-related molecular clusters were identified in the ESRD samples. Cluster2 was more correlated with the immune infiltration of ESRD. By analyzing the intersection points between CRG cluster and key genes of ESRD, a total of 888 specific DEGs were identified. Functional differences related to specific DEGs were further explored using gene set variation analysis. Five significant genes (SMC5, USP47, USP53, AGA, and DMXL1) were identified by the support vector machine model as key predictors for ESRD disease risk, achieving an area under the curve (AUC) of 1.00 in internal validation. However, external validation in independent cohorts is required prior to clinical application. Individual gene analysis showed an AUC > 0.81 in discriminating ESRD patients from healthy controls, and the expression of all 5 genes in ESRD patients was significantly lower than in the control group. CONCLUSION: This study clarified the relationship between CRGs and the phenotype of ESRD, analyzed their specific roles in the immune microenvironment, and obtained a predictive model, providing new insights for the study of its potential therapeutic targets.

Humans↗

PubMed2026

Three-Year Experience of Cytogenetic and Molecular Genetic Evaluation in Patients With Disorders of Sex Development at a Tertiary Care Centre in Eastern India.

OBJECTIVES: Disorders of sex development (DSD) include a range of conditions in which chromosomal, gonadal, or anatomical sex deviates from the typical developmental pathway. The diagnostic approach to DSD has shifted from karyotyping to molecular genetic tools. This study evaluated the clinical presentation, cytogenetic spectrum, and diagnostic utility of conventional and advanced molecular genetic investigations in patients with suspected DSD managed at a tertiary care facility in Eastern India over a three-year period. METHODS: A retrospective observational study was conducted at the Genetics Laboratory of a tertiary care teaching hospital in Eastern India. Consecutive patients with clinically suspected DSD referred between January 2022 and December 2024 were included. Demographic and clinical data were obtained from referral records, and peripheral blood samples were analysed using standard G-banded karyotyping according to the International System for Human Cytogenomic Nomenclature (ISCN 2020). Fluorescence in situ hybridisation (FISH), chromosomal microarray analysis (CMA), and whole-genome sequencing (WGS) were selectively performed in cases with inconclusive cytogenetic findings, suspected structural chromosomal abnormalities, or complex phenotypes. RESULTS: A total of 98 suspected DSD cases were evaluated during the study period. The most frequent chromosomal constitution was 46,XY DSD (37, 37.8%), followed by 46,XX DSD (30, 30.6%) and sex chromosome DSD (21, 21.4%). Culture failure occurred in 10 (10.2%) samples. Advanced genetic techniques, including FISH, CMA, and WGS, improved diagnostic clarification in selected complex cases. CONCLUSION: This experience highlights the importance of integrating contemporary high-resolution technologies with conventional cytogenetics to enhance the assessment, counselling, and treatment of individuals with DSD.

chromosomal analysis↗

PubMed2025

The CAP/ACMG CYCGH proficiency testing program: 10 years in review.

PURPOSE: The College of American Pathologists has offered proficiency testing (PT) for the detection of copy-number variations (CNV) in the constitutional setting (CYCGH) since 2008. We review and summarize data from the CYCGH PT program, including participant performance over time, changes made to the program, and ungraded challenges. METHODS: The PT challenges from 2011 through 2021 (22 total mailings) and changes to the program over time were reviewed. Laboratory enrollment and performance were assessed. RESULTS: Overall participation has increased over time, and laboratories have maintained a high level of proficiency. The major changes to the program have occurred twice during the time span examined. Reasons for challenges not meeting consensus were varied. The use of ungraded challenges was also discussed. CONCLUSION: The CYCGH PT program is challenging because it assesses both analytical performance and interpretation as a single analyte. The program has evolved over time to address the changes in the field of CNV detection. During this time, additional technologies with the ability to detect CNVs have emerged, and the possibility of developing a platform-agnostic CNV PT program is being explored.

Humans↗