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At least 19 recordsLinked to original sources
PubMed2026

Oxidative Stress Associated LncRNAs as Potential Biomarkers for Prognosis and Immune Responses in Lung Squamous Cell Carcinoma Patients.

Long-chain non-coding RNA (lncRNA) significantly influences lung squamous cell carcinoma's (LUSC) prognostic value and immune infiltration. This study aimed to demonstrate how oxidative stress-related lncRNAs impact lung squamous cell carcinoma (SCC). The Cancer Genome Atlas (TCGA) dataset gathered transcriptome information and related clinical data for LUSC. To build a prognostic model, 10 prognostic-related genes were identified using a series of bioinformatics analyses that compared the OS gene's aberrant expression in tumor and healthy tissues, as well as its association with malignancy. Subjects were stratified into high- and low-risk groups based on the median risk score derived from the 10-gene signature. While the mathematical risk model demonstrated limited independent predictive performance in the validation cohort (AUC ~ 0.5), functional and immunological evaluations revealed significant differences in the tumor microenvironment (TME) across risk strata. Specifically, high-risk patients exhibited distinct immune infiltration profiles and altered immunological scores relative to their low-risk counterparts. Therefore, rather than serving as a direct clinical prediction tool, this oxidative stress-related lncRNA signature provides valuable biological insights into the immune landscape of LUSC and highlights potential therapeutic targets for further mechanistic investigation.

Humans↗
PubMed2004

Expression analysis of the human kallikrein 7 (KLK7) in breast tumors: a new potential biomarker for prognosis of breast carcinoma.

Kallikreins are a subgroup of serine proteases that are involved in the post-translational processing of polypeptide precursors. Growing evidence suggests that many kallikreins are implicated in carcinogenesis. Human kallikrein gene 7 (KLK7; HSCCE) is a new member of the human kallikrein gene family. KLK7 is expressed in normal breast tissue and is up-regulated in breast cancer cells by estrogens and glucocorticoids. In the present study, expression of the KLK7 gene in 92 breast cancer tissues was analyzed by reverse transcription-PCR (RT-PCR) and direct sequencing of several samples. The results were correlated with other clinicopathological variables and patient outcome. KLK7 gene expression was significantly lower in breast cancer patients of low stage (I/II) (p = 0.011) and patients with positive progesterone receptors (p = 0.022). Survival analysis showed that breast cancer patients with KLK7 positive tumors have relatively shorter disease-free survival (DFS) and overall survival (OS) than patients with KLK7 negative tumors. These data suggest that KLK7 gene expression may be used as a marker of unfavorable prognosis for breast cancer patients.

Adult↗
PubMed2004

Down-regulation of zeta-chain expression in T cells: a biomarker of prognosis in cancer?

The zeta chain is a 16-kDa molecule associated with the T-cell receptor (TCR)-CD3 complex in T lymphocytes and FcgammaRIII in CD3(-)CD56(+)CD16(+) natural killer (NK cells). The zeta chain functions as a transmembrane signaling molecule in lymphocytes. Expression of zeta was found to be decreased in CD4(+) and CD8(+) T lymphocytes isolated from the tumor site or from the peripheral circulation of patients with cancer. A quantitative flow cytometry-based assay for zeta-chain expression allows for reproducible serial evaluations of disease- or therapy-associated changes in expression of this signaling molecule in phenotypically defined subsets of immune cells. Semiquantitative evaluation of zeta expression in paraffin-embedded tissue specimens can link it to the conventional markers of prognosis or survival. Several distinct mechanisms may be responsible for decreased/absent zeta in T cells of patients with cancer. Monitoring for zeta expression is useful for assessing immune competence in these patients and for following changes in immune competence during anticancer therapies. Correlations made between clinical findings, pathologic results, and zeta expression in immune cells suggest that low/absent zeta is predictive of poor prognosis and survival in patients with cancer. Thus, zeta is emerging as a clinically relevant signaling molecule, which also seems to predict a favorable response to biologic therapies and could be helpful in a selection of patients for immunotherapy trials. Validation studies have yet to be performed for this putative immunologic biomarker. Its consistent use for monitoring under standardized conditions of cancer patients treated with biotherapies may help in confirming a role for zeta as a correlate of prognosis or survival.

Animals↗
PubMed1997

p53-protein and Ki-67-antigen expression are both reliable biomarkers of prognosis in thick stage I nodular melanomas of the skin.

The maximum tumour thickness is the most important prognostic factor in malignant melanomas of the skin. However, the clinical outcome of thick nodular melanomas remains unpredictable. Therefore, we investigated possible prognostic markers in this subset of melanomas. From a melanoma data base, 12 patients with thick (> 3 mm) stage I nodular melanomas of the skin were identified, who were still without signs of progression after five years of follow-up. These tumours were compared to randomly selected series of 12 cases, who did not survive the first five years after removal of the tumours. We performed immunostaining for the p53-protein and the proliferation associated Ki-67-antigen. For quantification of immunostaining the tumours were entirely scanned. In addition, all tumours were investigated for any differences with conventionally applied prognostic features: the tumour thickness: the level of invasion; the prognostic index (tumour thickness multiplied by mitotic count); and the mean volume-weighted mean nuclear volume. We demonstrated significant differences between survivors and non-survivors exclusively in respect of the staining indices for p53 and Ki-67 (P < 0.03 and 0.02, respectively). With both antibodies the tumours of survivors showed lower counts as compared to non-survivors survivors. However, within both groups we found no significant correlations between the p53- and Ki-67-staining results. We conclude that immunostaining for p53-protein and Ki-67-antigen is helpful to identify individuals with thick nodular melanomas who are at risk of metastatic disease.

Adult↗
PubMed2024

Use of extracellular vesicle microRNA profiles in patients with acute myeloid leukemia for the identification of novel biomarkers.

OBJECTIVES: This study aimed to establish clinically significant microRNA (miRNA) sets using extracellular vesicles (EVs) from bone marrow (BM) aspirates of patients with acute myelogenous leukemia (AML), and to identify the genes that interact with these EV-derived miRNAs in AML. MATERIALS AND METHODS: BM aspirates were collected from 32 patients with AML at the time of AML diagnosis. EVs were isolated using size-exclusion chromatography. A total of 965 EV-derived miRNAs were identified in all the samples. RESULTS: We analyzed the expression levels of these EV-derived miRNAs of the favorable (n = 10) and non-favorable (n = 22) risk groups; we identified 32 differentially expressed EV-derived miRNAs in the non-favorable risk group. The correlation of these miRNAs with risk stratification and patient survival was analyzed using the information of patients with AML from The Cancer Genome Atlas (TCGA) database. Of the miRNAs with downregulated expression in the non-favorable risk group, hsa-miR-181b and hsa-miR-143 were correlated with non-favorable risk and short overall survival. Regarding the miRNAs with upregulated expression in the non-favorable risk group, hsa-miR-188 and hsa-miR-501 were correlated with non-favorable risk and could predict poor survival. Through EV-derived miRNAs-mRNA network analysis using TCGA database, we identified 21 mRNAs that could be potential poor prognosis biomarkers. CONCLUSIONS: Overall, our findings revealed that EV-derived miRNAs can serve as biomarkers for risk stratification and prognosis in AML. In addition, these EV-derived miRNA-based bioinformatic analyses could help efficiently identify mRNAs with biomarker potential, similar to the previous cell-based approach.

Humans↗
PubMed2004

[Significance of p53 gene mutation and P53 protein expression abnormality on the prognosis of esophageal cancer: a meta-analysis study].

OBJECTIVE: To evaluate the prognostic significance of p53 mutation and P53 protein expression abnormality among esophageal cancer. METHODS: The results of 27 random controlled trials from 1990 to 2003 were analyzed by meta-analysis method. The overall positive rate of p53 was 52.9% among the cumulative 2174 cases. Relative hazard (RH) was applied to evaluate the risk of disease and all data were analyzed by Dersimonian-Laird method. RESULTS: The analysis for homogeneity (q statistics test) showed that all eligible studies were with heterogeneity (q = 59.88, P < 0.005). The combined RH was 2.07 and 95% confidence interval was 1.58-2.70. CONCLUSION: Findings showed that p53 was a poor prognosis biomarker for esophageal cancer gene diagnosis but might benefit to the strategy of treatment.

Carcinoma, Squamous Cell↗
PubMed2001

p53 protein in esophageal mucosa of individuals at high risk of squamous cell carcinoma of the esophagus.

Squamous cell carcinoma of the esophagus (SCCE) is diagnosed late and carries a poor prognosis. Biomarkers such as p53 protein expression may be present in the esophageal mucosa long before esophageal symptoms or lesions appear and may point toward early diagnosis. Asymptomatic subjects at high risk for SCEE (consumption of more than 80 g of ethanol and 10 cigarettes/day for at least 10 years) underwent upper gastrointestinal endoscopy with biopsies of the esophageal mucosa, and expression of p53 protein was compared with conventional histologic findings. In 182 subjects studied, p53 protein was expressed in a stepwise fashion according to the severity of the histologic findings: normal mucosa (12/103 or 11.7%), mild chronic esophagitis (6/43 or 14%), moderate chronic esophagitis (4/18 or 22.2%), severe chronic esophagitis (1/3 or 33.3%), low-grade dysplasia (4/11 or 36.4%), high-grade dysplasia (2/2 or 100%), and squamous cell carcinoma (2/2 or 100%) (P=0.00025). The odds ratio and confidence intervals were calculated by logistic regression, with multivariate adjustment for potentially confounding variables. The risk for p53 expression was twofold for moderate and severe chronic esophagitis and 10-fold for dysplasia and cancer (P=0.001). p53 protein was expressed not only in cancerous lesions, high-grade and low-grade dysplasia, as expected, but also in mucosa considered normal or with chronic esophagitis using conventional histology. Smokers and alcohol drinkers with normal mucosa or chronic esophagitis that express p53 protein may represent an unrecognized subgroup of individuals that may benefit from surveillance. Follow-up studies of these asymptomatic subjects and molecular analysis of the p53 gene are needed to clarify this point.

Adult↗
PubMed2002

Increased urinary F2-isoprostanes in patients with Crohn's disease.

OBJECTIVES: Reactive oxygen metabolites have been suggested to participate in the pathogenesis of Crohn's disease, but the evidence supporting this contention in vivo is incomplete. Isoprostaglandin F2alpha type III (iPF2alpha-III, or 15-F2t-IsoP) is a prostaglandin F2alpha isomer produced in vivo by free radical-catalyzed peroxidation of arachidonic acid. We aimed to investigate urinary iPF2alpha-III concentrations as an index of lipid peroxidation in 23 patients with Crohn's disease compared with 23 healthy controls, and to test whether lipid peroxidation correlates to clinical relapse and inflammation. METHODS: Urinary iPF2alpha-III was measured by gas chromatography/electronic impact mass spectrometry. RESULTS: Urinary iPF2alpha-III concentrations were significantly higher in patients with Crohn's disease than in healthy controls (median [range] = 130 [38-622] vs 91 [35-152] pmol/mmol of creatinine, respectively; p < 0.01). There was a trend toward significance for patients with clinical relapse versus patients with clinical remission (median [range] = 155 [38-622] vs 96 [64-253] pmol/mmol of creatinine, respectively; p = 0.09). A significant correlation was found between urinary iPF2alpha-III and plasma C-reactive protein concentrations, suggesting a link between lipid peroxidation and inflammation. CONCLUSION: This study provides evidence of increased lipid peroxidation in patients suffering from Crohn's disease, especially in patients with clinical relapse. iPF2alpha-III quantification has to be investigated as a prognosis biomarker in patients suffering from Crohn's disease.

Adolescent↗
PubMed2025

Molecular analysis of lung adenocarcinomas from the SAFIR02-Lung cohort reveals new metastasis-associated copy-number alterations including frequent mutant-specific KRAS-allelic imbalance and identifies CDKN2A homozygous deletions as an independent biomarker of poor prognosis.

BACKGROUND: Identifying molecular alterations specific to advanced lung adenocarcinomas could provide insights into tumour progression and dissemination mechanisms. METHOD: We analysed tumour samples, either from locoregional lesions or distant metastases, from patients with advanced lung adenocarcinoma from the SAFIR02-Lung trial by targeted sequencing of 45 cancer genes and comparative genomic hybridisation array and compared them to early tumours samples from The Cancer Genome Atlas. RESULTS: Differences in copy-number alterations frequencies suggest the involvement in tumour progression of LAMB3, TNN/KIAA0040/TNR, KRAS, DAB2, MYC, EPHA3 and VIPR2, and in metastatic dissemination of AREG, ZNF503, PAX8, MMP13, JAM3, and MTURN. Conversely, no meaningful difference was found in pathogenic single-nucleotide variant frequencies, reinforcing the notion that they are early events in tumorigenesis. CDKN2A homozygous deletion was linked to poor clinical outcome in patients with early tumours (overall survival hazard ratio 2.17, 95% CI: 1.43-3.28, corrected p-value&#x2009;=&#x2009;0.01). Furthermore, we found that KRAS mutant allele specific imbalance, i.e. focal amplification of the mutant allele, is more prevalent in locoregional or distant samples of metastatic patients than in early lesions (8.4%, 13% and 2.8% respectively). This observation was replicated in three public cohorts. Tumours with KRAS mutant allele specific imbalance show specific patterns of co-occurrence and mutual exclusion with alterations in key cancer genes like CDKN2A, TP53, STK11 and NKX2-1, often in a tumour type dependent manner. CONCLUSION: Advanced LUAD tumours exhibit higher copy-number alteration burden, with distinct alterations associated with tumour progression and metastasis. CDKN2A homozygous deletions predict poor prognosis in early disease, while KRAS mutant allele-specific imbalance is enriched in advanced tumours.

Humans↗
PubMedDate not supplied

Combined evaluation of NGF and p75NGFR expression is a biomarker for predicting prognosis in human invasive ductal breast carcinoma.

Nerve growth factor (NGF) is a member of the neurotrophin family and is essential for the differentiation and maintenance of neural cells. Recently, it has been reported that NGF is involved in the growth of breast cancer. On the other hand, two types of NGF receptors have been identified, a low-affinity receptor, p75NGFR, and a high-affinity receptor, TrkA. NGF-p75NGFR interaction is known to play an important role in apoptosis, whereas NGF-TrkA interaction is responsible for the survival of neural cells. We examined the relationship between clinicopathological factors, Ki-67 index, apoptotic index and the immunohistochemical expression of NGF, TrkA and p75NGFR in 71 invasive ductal breast carcinoma (IDBC) specimens. Our data indicate that positive Ki-67 expression (a labeling index exceeding 30%) correlates significantly with the positive expression of NGF (p=0.0091). Moreover, the apoptotic index was found to correlate with a strong expression of p75NGFR. Furthermore, patients who were NGF positive and p75NGFR negative had significantly poorer disease-free survival rates (p=0.0165). In contrast, those who were NGF negative and p75NGFR positive had significantly more favorable outcomes (p=0.0191). These findings suggest that a combined evaluation of NGF and p75NGFR expression is a predictive factor in the prognosis of IDBC patients.

Adult↗
PubMed2003

Nuclear BAG-1 expression is a biomarker of poor prognosis in esophageal squamous cell carcinoma.

Apoptosis is one of the critical biological factors that correlate with the biological behavior of malignant tumors including cancer progression and clinical outcome. The present study was performed to clarify the clinical implications of BAG-1, a bcl-2 binding protein in esophageal squamous cell carcinoma (ESCC). Seventy-one cases with ESCC were investigated. Immunohistochemical study of BAG-1 was performed on resected specimens. The expression pattern of BAG-1 in nuclei and/or cytoplasm was analyzed and correlated with TNM classification, vessel invasion, survival period after surgery. BAG-1 expression in the nuclei was related to the depth of tumor invasion (P = 0.0381) but not to any other clinicopathologic parameters. The cytoplasmic staining pattern of BAG-1 exhibited no correlation with clinicopathologic parameters. Univariate analysis (P < 0.05), but not multivariate analysis, revealed significantly poor prognosis for ESCC cases exhibiting positive nucleic staining for BAG-1. Our data suggests that BAG-1 expression in the nuclei of ESCC plays an important role in tumor development and may be useful for predicting the prognosis after surgery.

Biomarkers, Tumor↗
PubMed2006

Amino-terminal pro-brain natriuretic peptide: a biomarker for diagnosis, prognosis and management of heart failure.

There is a substantial need for a diagnostic tool to aid in the early diagnosis of heart failure and in the recognition of those at risk for its development, as well as in guidance of therapy. Testing for amino-terminal pro-brain natriuretic peptide (NT-proBNP) has been recognized to have utility in the diagnosis, prognosis and management of heart failure. In addition, numerous other applications for NT-proBNP testing are now recognized, such as evaluation of patients with heart disease in the absence of heart failure, as well as the diagnostic and prognostic evaluation of patients with acute coronary syndromes or pulmonary thromboembolism.

Algorithms↗
PubMedDate not supplied

[Biomarkers in the prognosis and treatment response of breast cancer].

PURPOSE: To determine the prognostic value of c-erbB-2, p53, hormone receptors and angiogenesis, on recurrence free time and its relationship to treatment in breast cancer patients. METHODS: Women with histologic diagnosis of breast cancer and immunohistochemical determination of biologic factors. Clinic, histologic, molecular factors and recurrence free time were registered. RESULTS: 101 patients, ages 51.98 +/- 11.5 years. Follow-up 32.52 +/- 24.3 months. Tumor recurred in 31, (30.69%); 15 (48.33%) had tumor size above 2.1 cm, 19 (61.29%) showed positive estrogen receptors and 18 (58.07%) for progesterone; 20 (64.51%) to c-erbB-2 expression (64.51%); 18 to p53; average microvessels 24.48 +/- 17.27. Tumor size related to recurrence, p = 0.008. Kruskal-Wallis test did not show a difference when correlating survival free time and biologic factors. 24 pts. (77.41%) received hormones; 20 (64.5%) chemotherapy (61.29%); 19 (61.29%) radiotherapy. Response prediction to hormones with estrogen receptor positive, p = 0.059; to chemotherapy in angiogenesis under 40 vessels/field-0.024. CONCLUSIONS: Tumor size has prognostic implications. A clear positive tendency was observed with p53 and higher microvessel density. Estrogen receptors offer predictive response value to hormone treatment and lower vascular density to chemotherapy, treatment indicators of possible therapeutic association.

Adult↗
PubMed2026

Targeting RELA and STAT3 regulates TNFRSF10A-mediated apoptosis in a novel apoptosis-based prognostic model for clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal malignancy and remains a major cause of cancer-related mortality worldwide. Although advances in surgery, targeted therapy, and immunotherapy have improved outcomes for patients, reliable biomarkers for predicting prognosis remain limited. Therefore, robust gene-based prognostic models are urgently needed to improve risk stratification and guide individualized treatment strategies. METHODS: We developed a novel prognostic model integrating apoptosis and immune - related genes (AIRGs) to predict overall survival (OS) in patients with ccRCC. RESULT: Using Gene Set Enrichment Analysis (GSEA) combined with least absolute shrinkage and selection operator (LASSO) Cox regression, we identified 7 key prognostic genes, namely, CCR4, TNFRSF10A, TEK, TGFA, CD14, IFITM1, and SEMA3G, that collectively demonstrated strong predictive performance in TCGA cohort with c-index&#x2009;=&#x2009;0.711. Functional enrichment analyses revealed that apoptosis, immune regulation, and multiple oncogenic signaling pathways were significantly associated with the risk score, highlighting the critical role of the tumor microenvironment in ccRCC progression. Transcription factor binding analysis based on the JASPAR database suggested that RELA and STAT3 with scores of 0.829 and 0.951, respectively are potential upstream regulators within the prognostic network, particularly influencing TNFRSF10A expression. External validation using the International Cancer Genome Consortium (ICGC) dataset confirmed the robustness of the prognostic model with c-index&#x2009;=&#x2009;0.612 Furthermore, in vitro experiments demonstrated that RELA and STAT3 regulate TNFRSF10A-mediated apoptotic signaling in ccRCC cells, providing mechanistic support for the bioinformatic findings. CONCLUSION: This study establishes a biologically informed and clinically relevant prognostic framework for ccRCC. Our findings highlight the therapeutic potential of targeting the RELA/STAT3-TNFRSF10A axis and contribute to the advancement of precision medicine in ccRCC.

Humans↗
PubMed2026

Protein Biomarkers in Risk and Prognosis of Amyotrophic Lateral Sclerosis.

BACKGROUND: Plasma and cerebrospinal fluid (CSF) protein biomarkers in amyotrophic lateral sclerosis (ALS) may provide insight into disease mechanisms and yield clinically useful biomarkers. METHODS: Overall, 363 proteins in plasma and CSF from 198 patients with ALS and 125 matched controls were profiled using Olink assays. Associations with disease status, survival, and functional decline, as well as longitudinal biomarker stability across the disease course were assessed, together with network and enrichment analyses. ALS risk-associated biomarkers were externally validated in the UK Biobank (UKB). RESULTS: Overall, 125 proteins were significantly associated with at least one outcome (i.e., case status, risk, survival, or functional decline), and 21 were associated with three or more outcomes. NEFL was the most robust biomarker in plasma and CSF, alongside TNFRSF12A in plasma and CSF, EDA2R in plasma, and FABP4 in plasma and CSF. Most biomarkers remained stable longitudinally across the disease course. ALS risk-associated biomarkers were replicated in UKB, in which >&#x2009;3000 plasma proteins were measured in 52,990 participants, including 298 with ALS. Network and enrichment analyses highlighted their roles in immune response and extracellular-matrix remodeling, and their enrichments in the brain and T-cell subsets. Construction of an ALS risk-prediction model achieved an ROC-AUC of 0.72 in the UKB validation cohort. CONCLUSIONS: These findings suggest candidate protein biomarkers for ALS risk stratification, early detection, and clinical therapeutic monitoring.

Humans↗
PubMed2003

Human kallikrein 6 (hK6): a new potential serum biomarker for diagnosis and prognosis of ovarian carcinoma.

PURPOSE: The discovery of new ovarian cancer biomarkers that are suitable for early disease diagnosis and prognosis may ultimately lead to improved patient management and outcomes. PATIENTS AND METHODS: We measured, by immunoassay, human kallikrein 6 (hK6) concentration in serum of 97 apparently healthy women, 141 women with benign abdominal diseases, and 146 women with histologically proven primary ovarian carcinoma. We then calculated the diagnostic sensitivity and specificity of this test and examined the association of serum hK6 concentration with various clinicopathologic variables and patient survival. RESULTS: Serum hK6 concentration between normal and benign disease patients was not different (mean, 2.9 and 3.1 micro g/L, respectively). However, hK6 in presurgical serum of ovarian cancer patients was highly elevated (mean, 6.8 micro g/L; P <.001). Serum hK6 decreased after surgery (to a mean of 3.9 micro g/L) in 68% of patients. The diagnostic sensitivity of serum hK6 at 90% and 95% specificity is 52% and 47%, respectively, in the whole patient population. For early stage disease (stage I or II), sensitivity is approximately 21% to 26%. When combined with CA-125, at 90% specificity, sensitivity increases to 72% (for all patients) and to 42% in stage I or II disease. Serum hK6 concentration correlates moderately with CA-125 and is higher in patients with late-stage, higher-grade disease and in patients with serous histotype. Preoperative serum hK6 concentration is a powerful predictor of disease-free and overall survival in both univariate and multivariate analyses. CONCLUSIONS: Serum hK6 concentration seems to be a new biomarker for ovarian carcinoma and may have value for disease diagnosis and prognosis.

Adult↗