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PubMed1989

[Proliferation index, axillary lymph node status, hormone receptors and age as prognostic factors in primary breast cancer].

A total of 233 primary carcinomas of the breast (n = 68 nodal negative and n = 165 nodal positive) of 77 woman patients of less than 50 years of age and pf 156 women patients of 50 years of age or older were examined for the prognostic significance of a proliferation index (in vitro chemoresistance assay). The prognostic significance of the proliferation index (high vs low proliferation) is compared with other prognostic factors that have already been in clinical use (age, axillary lymph node status, oestrogen and progesterone receptor status). The total median observation period was 4.8 years (3-9.1 years). Determination of the proliferation index proved to be the most important prognostic factor both for premenopausal and postmenopausal, nodal negative and nodal positive primary tumours when assessing the total survival time and the time that remains free from recurrences. A simultaneous assessment of low proliferation index and positive hormone receptor as a so-called low-risk situation shows in comparison to a high-risk situation (high proliferation index, negative receptor status) the most pronounced differences. For premenopausal women (younger than 50 years of age) the hormone receptor status has no prognostic significance as far as our group of patients is concerned, whereas for women of 50 years of age or older the receptor status is of great prognostic relevance. Besides the lymph node status, the proliferation index shows in a Cox regression model the greatest prognostic importance for the further course of a primary carcinoma of the breast.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1991

Prognosis and breast cancer. Recognition of lethal and favorable prognostic types.

Assignment of breast cancer patients to specific prognostic groups has been a relatively empty exercise until the recent acceptance of the effectiveness of systemic chemotherapy. The previous question of who should be so treated has changed in North America to a question of who should not be so treated. The availability of intensive chemotherapy for the worst prognostic groups as well as efficacious, low-toxicity adjuvant chemotherapy has made prognostication mandatory. The current major question is which women with breast cancer will not benefit from chemotherapy. We are actually much better at prognostication than many studies and the current broad search for new prognostic markers would indicate. The assignment of excellent prognosis categories by defined special histologic types or grade of breast cancer as well as other measures recognize women with survival approaching or equaling the general population. Likewise, extremely poor prognosis may be recognized in 20% to 40% of women with breast cancer by the presence of extensive mitoses or high proliferation index (by any modality) and poor differentiation (highest grade). Combined tumor size and nodal status data with high-grade indicates that women with these indicators will die within 2 to 3 years with as high as 80% certainty. The surgical pathologist still determines if cancer is present and must also determine if the tumor is in situ or invasive, its type or grade if invasive, and the extent of in situ component. Considering the diminution in overall size of cancers detected by modern techniques, it is clear that validation of newer prognostic variables will be more useful and will allow more separate determinations if adapted to tissue sections rather than tissue homogenates. The many measures of these carcinomas, such as size and nodal status, make multiparametric assessment of putative prognostic markers mandatory.

Biomarkers, Tumor↗

PubMed1994

Prognostic factors predictive of survival and local recurrence for extremity soft tissue sarcoma.

OBJECTIVE: The authors sought to identify prognostic factors in the management of extremity soft tissue sarcoma. SUMMARY BACKGROUND DATA: The surgical management of soft tissue sarcoma has evolved because of advances in therapy, resulting in increased limb preservation and quality of life. However, identifying a subset of patients most likely to benefit from adjuvant chemotherapy has been difficult to achieve. METHODS: A retrospective analysis of a prospective data base of 182 patients with extremity sarcomas from 1970 to 1992 was performed. RESULTS: A histologic diagnosis of Ewing's sarcoma, synovial sarcoma, and angiosarcoma was associated with a 13-fold increased risk of death compared with liposarcoma, fibrosarcoma, and malignant peripheral nerve sheath histologic types after having adjusted for the other prognostic factors (p < 0.001). In addition to histologic type, high-grade sarcomas (p = 0.018), sarcomas greater than 10 cm in size (p = 0.006), and age at diagnosis (p = 0.016) were found to be important prognostic factors for survival but not for local recurrence. For the first time to their knowledge, the authors showed that mean mitotic activity has prognostic value after having adjusted for other prognostic factors, such as grade (p = 0.005). The only prognostic factors predictive for local recurrence were whether the patient presented with locally recurrent disease (p = 0.0001) or had microscopically positive margins (p = 0.052). CONCLUSIONS: The use of mitotic activity along with grade, size, histologic type, and age at diagnosis is prognostic for survival in extremity soft tissue sarcoma. The use of an objective pathologic feature, such as mean mitotic activity, is also useful in selecting patients for future systemic neoadjuvant or adjuvant trials and primary therapy.

Adolescent↗

PubMed1995

Prognostic factors predictive of survival for truncal and retroperitoneal soft-tissue sarcoma.

OBJECTIVE: The authors identified prognostic factors relevant to clinical outcomes (especially survival) in truncal and retroperitoneal soft-tissue sarcoma. SUMMARY BACKGROUND DATA: These results can be used to optimize surgical management and select patients most likely to benefit from novel therapeutic strategies in future trials. METHODS: A retrospective analysis was performed of a prospectively compiled database of 183 consecutive patients with truncal and retroperitoneal sarcomas seen at the Brigham and Women's Hospital and the Dana Farber Cancer Institute between 1970 to 1994. RESULTS: For truncal sarcoma, multivariate analysis showed that high-grade histology was associated with an eightfold increased risk of death compared with low-grade histology (p = 0.001). In addition to grade, gross positive margin of resection (p = 0.001), microscopic positive margin (p = 0.023), and tumors greater than 5 cm in size (p = 0.018) were important independent prognostic factors for survival. In this series, postoperative radiation therapy for truncal sarcoma was associated with a 2.4-fold decreased risk of death compared with truncal sarcoma patients receiving no adjuvant radiation therapy, having adjusted for the other prognostic factors (p = 0.030). In contrast, for retroperitoneal sarcoma, multivariate analysis showed that high-grade and intermediate-grade histology were associated with a five- to sixfold increased risk of death compared with low-grade histology (p = 0.009). In addition to grade, gross positive margin of resection (p = 0.001) and microscopic positive margin (p = 0.004) were important independent prognostic factors for survival in retroperitoneal sarcoma. Patients who received either preoperative or postoperative chemotherapy for retroperitoneal sarcoma had a 4.6-fold (p = 0.002) and 3-fold (p = 0.010) increased risk of death, respectively, compared with patients receiving no adjuvant chemotherapy, having adjusted for the other prognostic factors. CONCLUSIONS: The histologic grade and the margin of resection are prognostic for survival in both truncal and retroperitoneal soft-tissue sarcoma. Tumor size was an independent prognostic factor for truncal sarcoma, but not for retroperitoneal sarcoma. Postoperative adjuvant radiation was beneficial to overall survival for truncal sarcoma. In this series of patients receiving a heterogeneous mixture of chemotherapeutic regimens-either as preoperative "neoadjuvant" therapy or as postoperative "adjuvant" therapy, there were no beneficial effects on survival compared with nonrandomized patients not receiving chemotherapy.

Adult↗

PubMed1993

Serum thymidine kinase as a prognostic indicator for patients with multiple myeloma: results from the MRC (UK) V trial.

The significance of serum thymidine kinase (STK) as a prognostic indicator for patients with myeloma has been evaluated by determining the pre-treatment level of STK in a retrospective study of 547 patients from the Medical Research Council (MRC) V Myeloma Trial. Overall, STK was a highly significant prognostic factor (Chi 2 = 7.91; P = 0.005). At the time of censor, 23.4% of patients with a presentation STK of < 6 U/l but only 7.9% of the patients with an STK of > 11 U/l were still alive. STK proved to be a highly significant prognostic indicator for the 270 melphalan-treated patients (Chi 2 = 12.37; P = 0.0004) but had no prognostic significance for the 277 ABCM (adriamycin, BCNU, cyclophosphamide and melphalan) treated patients (Chi 2 = 0.29; P = 0.59). When the STK data was stratified for serum B-2-microglobulin (SB2M) it was demonstrated that STK was independent of SB2M and provided additional prognostic information for patients who were treated with melphalan. Thus patients with both a low STK and SB2M had the best prognosis (median survival 1677 d) and those patients with a high STK and SB2M had the worst prognosis (median survival 519 d). STK is a good prognostic marker for patients treated with melphalan but the prognostic significance of STK may disappear with the introduction of new chemotherapy regimens.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1996

A survival regression analysis of prognostic factors in colorectal cancer.

BACKGROUND: Many prognostic factors of colorectal cancer are known but their actual clinical validity is still uncertain. The aim of the present study was to verify, on the basis of our experience, the prognostic validy of variables for survival by using survival regression analysis. METHODS: From January 1978 to December 1986 the prognostic factors for 192 patients were analysed. These patients had undergone surgical resection for colorectal cancer. The follow up was completed in every patient by the end of December 1992, with a median follow up of 10 years (range 6-14 years). The prognostic factors considered in the statistical analysis were age, sex, size of tumour, site, grade, direct spread, node involvement and stage (according to Astler-Coller and pTNM). RESULTS: Of the prognostic factors, sex was the only one not to show any prognostic significance. In the survival regression analysis we have used an accelerated failure time model (equivalent to the Cox proportional hazard model); age, grade and stage were significant covariables. CONCLUSIONS: Although clinical pathological staging (pTNM) appears as a pre-eminent prognostic factor, and as our analysis shows, it needs a further variable (grading), which has been shown to affect the prognosis in a significant way.

Adult↗

PubMed1995

[Immunohistologic tumor cell detection in lymph nodes in node negative breast cancer: correlation with "established" and "recent" prognostic factors].

OBJECTIVES: The prognostic value of immunohistochemically detected micrometastases in lymph nodes as well as its association with newer prognostic factors is discussed controversially. PATIENTS AND METHODS: Using a monoclonal pancytoceratine antibody 1807 axillary lymph nodes of 122 pT1-2N0M0-patients were examined. Histological findings, established and newer prognostic factors were investigated additionally. The mean follow up time was 50 months. RESULTS: The detection of micrometastases in 16 of 122 (13.1%) patients were related with a prognostic disadvantage for recurrence free survival (p = .03). Tumour size, grading, vessel invasion and S-phase, but not the detection of micrometastases, were confirmed as independent prognostic factors in nodal negative patients by Cox-regression. CONCLUSION: Immunohistochemically detected micrometastases in axillary lymph nodes are of prognostic and therapeutic value but they are not independent prognostic factors.

Biomarkers, Tumor↗

PubMed2026

Prognostic value of genes associated with metastasis and propionate metabolism in rectal cancer.

BACKGROUND: Research indicates that alterations in propionate metabolic pathways play a critical role in cancer development and invasion. Postoperative metastatic recurrence remains a major cause of mortality in patients with rectal cancer. However, propionate metabolism-related genes (PMRGs) in rectal cancer remain insufficiently characterized. Therefore, this study aimed to identify prognostic biomarkers associated with lymph node metastasis and propionate metabolism and construct a risk‑prediction model for rectal cancer via bioinformatic analyses. METHODS: The Cancer Genome Atlas-Rectum Adenocarcinoma (TCGA-READ) and GSE87211 datasets, together with a curated PMRGs gene set, were used in this study. Pearson correlation analysis was performed to assess associations between overlapping genes (differentially expressed genes between READ and normal tissues, as well as between N0 and N1-N2 stages) and PMRGs, leading to the identification of candidate genes. Functional enrichment analyses were subsequently conducted to characterize the biological roles of these candidates. Prognostic biomarkers were identified using univariate Cox regression combined with least absolute shrinkage and selection operator (LASSO) regression, and a prognostic model was constructed accordingly. Independent prognostic validation was then performed. In addition, immune checkpoint profiling and immunotherapy response analyses were conducted across risk subgroups. Single-gene Gene Set Enrichment Analysis (GSEA) was applied to elucidate the pathways associated with the identified biomarkers. Finally, drug sensitivity analyses were performed. RESULTS: A total of 157 candidate genes were identified through the analytical pipeline. Functional enrichment analysis indicated that these genes were primarily involved in inflammatory response regulation and tumor necrosis factor (TNF) signaling pathways. Five prognostic biomarkers were subsequently identified and incorporated into a predictive model. External validation using the GSE87211 cohort confirmed the robustness of the model. Risk score and disease status were identified as independent prognostic factors. Six immune checkpoint molecules exhibited differential expression between risk groups. Correlation analyses revealed that the risk score was positively associated with most immune checkpoint genes. Single-gene GSEA demonstrated that the biomarkers were mainly enriched in ribosomal biogenesis and cell adhesion molecule-related pathways. Furthermore, 51 therapeutic agents exhibited significantly different half-maximal inhibitory concentration (IC50) values between risk subgroups. CONCLUSIONS: This study identified five biomarkers (CCL24, IGFBP3, ODC1, PYGM, and VKORC1) associated with lymph node metastasis and propionate metabolism pathways, providing a potential foundation for prognostic prediction in patients with rectal cancer.

Rectal cancer↗

PubMed1991

Prognostic impact of stress testing in coronary artery disease.

Observational data prospectively collected permit the examination of a complex set of decisions, including the decision not to perform any stress testing. Patients with or without previous myocardial infarction admitted for coronary evaluation and not submitted to any stress testing because of clinical reasons are at a higher risk for subsequent death. For prognostication, no test has been better validated than exercise electrocardiography: it can identify patients at low and high risk for future cardiac events among those without symptoms, with typical chest pain, and with previous myocardial infarction. In patients with triple-vessel disease, the results of exercise also allow those at low and high risk to be recognized. Both exercise radionuclide angiography and 201Tl scintigraphy (the latter in larger patient populations) have also demonstrated significant prognostic value on patients with or without previous myocardial infarction. Neither one has shown superiority to the other in prognostication. So far, they have been considered the only viable alternatives to exercise electrocardiography stress testing for diagnosis and prognostication. However, their costs limit their extensive application. Preliminary data suggest that intravenous dipyridamole echocardiography can be used for both diagnosis and prognostication of coronary artery disease; moreover, the prognostic information derived from dipyridamole echocardiography testing seems independent of and additive to that provided by exercise electrocardiography. Further prospective studies on larger patient populations are needed to better define the prognostic value of dipyridamole echocardiography testing.

Cardiology↗

PubMed1984

Diffuse proliferative lupus glomerulonephritis. Determination of prognostic significance of clinical, laboratory and pathologic factors.

Clinical, laboratory and pathological factors in 35 females with diffuse proliferative lupus glomerulonephritis were analyzed to determine the prognostic significance of the individual variables. The clinical and laboratory variables were age, serum creatinine (Cr), serum C3, serum C4 and proteinuria at the time of biopsy while the biopsy ones included intraglomerular monocytic infiltration (NSE index), total glomerular deposits, extent of subendothelial deposits, extent of extraglomerular deposits, tubulo-interstitial inflammation, relative tubulo-interstitial volume and total pathologic score. Standard morphometric and counting procedures were used to determine the levels of all pathologic variables but pathologic score and extra glomerular deposits where grading estimates were done. Survival curves were determined by the life table method. Logrank and chi-square tests were used to establish levels of statistical significance. Seven patients developed established renal failure (Cr greater than or equal to 2.0 on two or more occasions at least 3 months apart) and nine showed significant deterioration of renal function (decrease in CrCl of 25% or more in between biopsy and last follow-up visit or an increase in serum Cr of 0.4 mg/dl or more over the follow-up period). The 5-year renal survival rate (absence of established renal failure) for the whole group was 77%. Serum Cr (p less than .005) and extent of extraglomerular deposits (p less than .025) were shown to be significant prognostic factors for renal survival. Of the seven patients who developed renal failure none had an NSE index greater than 3.0 and one had a C3 greater than or equal to 45 mg/dl. Statistically these factors were weak prognostic indicators (0.5 less than p less than .1). Multivariate analysis demonstrated that the extraglomerular deposit factor contributed significant additional prognostic information to that provided by Cr. Although not important as a prognostic factor on its own, the NSE index significantly improved the prognostic performance of serum Cr. The product of the NSE index and serum C3 proved to be a strong prognostic factor (p less than .005).

Adolescent↗

PubMed1994

[Initial prognostic factors of aneurysmal subarachnoid hemorrhage].

The purpose of this retrospective study is to explain, using a total of 210 consecutive patients with aneurysmal subarachnoid hemorrhage, the survival by several prognostic factors measured at the admission time. A multivariate analysis using the Cox proportional hazards model allowed one to recognize five prognostic factors: secondary arterial hypertension (risk ratio (RR) = 1.8; p = 0.03), the Hunt and Hess grade-3 (RR = 3.3; p = 0.002), the Hunt and Hess grade-4 (RR = 7.3; p = 0.007), and the hunt and Hess grade-5 (RR = 5.8; p = 0.03), the Fisher grade-3 (RR = 2; p = 0.01), and the Fisher grade-4 (RR = 2; p = 0.001). The determination of a prognostic score for each patient (using the coefficients of selected prognostic factors) allowed one to establish 3 prognostic stages with survival probabilities significantly different (p = 0.00005); stage-1; survival rate after 150 days (SR) = 97 %, confidence interval of 95 % (CI) = [0.90; 0.99], stage-2: SR = 66 %, CI = [0.56; 0.74], stage-3; SR = 34 %, CI = [0.17; 0.54]. The relative death risk for the stage-2 was 14 times higher than that for stage-1 (p = 0.00005), and the relative death risk for the stage-3 was 36 times higher than that for stage-1 (p = 0.00005). The age, the essential arterial hypertension, the sex and the angiographic classification of George have no prognostic value. The rebleeding incidence was correlated with prognostic stages (respectively from stage-1 to the stage-3: 8 %, 14 %, 34 %).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

[Prognostic value of 2 patient classification systems: APACHE II and diagnosis-related groups].

UNLABELLED: The APACHE II system classified patients on the basis of the severity of their disease, while the groups related with the diagnosis (DRG) are classified according to the consumption of resources. Nonetheless, the relative DRG weight (RWDRG) may be related with severity given that the most severe patients are also usually the most expensive. The aims of the study were: 1) verify the ability of DRG to measure clinical severity and 2) compare the prognostic value of both systems. METHODS: A transversal cut off was performed (316 consecutive admissions in intensive care units [ICU] with 23 exclusions due to unclear final evolution) with the patients being classified according to final hospital evolution in survivors and deaths. Each patient was given an APACHE II score corresponding to the first 24 hours in the ICU. Parallelly the cases were grouped in the corresponding DRG in accordance with the CIE-9-MC codification of their discharge report. The comparison of the means was carried out with the Student's t test, with the determination of prognostic values being performed by discriminant analysis. RESULTS: The survivors had an APACHE II score of 9.5 +/- 5.5 and the deaths of 22.5 +/- 7.8 (p < 0.0001). The RWDRG of the survivors was 1.4 +/- 0.9 and that of the deaths of 2.0 +/- 1.0 (p < 0.0001). On inclusion of all the patients the APACHE II prognostic value was 85.3% and the RWDRG 68.9% and both 84.6%. In the group of patients with a RWDRG lower than 1.6 the prognostic value of the APACHE II was of 87.6% and the RGRDW 72.0% and both 90%. In the group with RWDRG greater than 1.6 the prognostic value of the APACHE II was 85.1%, the RWDRG 73.0% and both 83.2%. CONCLUSIONS: The system of the groups related with diagnosis indirectly measures clinical severity. APACHE II is significantly superior to the system of groups related with diagnosis with regard to prognostic value. The use of both systems together does not improve the prognostic value of APACHE II.

Diagnosis-Related Groups↗

PubMed2026

Integrative analysis of the roles and prognostic value of RNA-binding proteins in papillary renal cell carcinoma.

RNA-binding proteins (RBPs) serve essential roles in various cancer types, but their functions in papillary renal cell carcinoma (pRCC) have not been elucidated to date. In our work, differentially expressed RBPs in pRCC were identified after acquisition of RNA-sequencing and clinical data related to pRCC from The Cancer Genome Atlas database(TCGA). Functional enrichment analysis and protein interaction network analysis, along with univariate and multivariate Cox regression analyses, were performed to uncover potential biological effects of the identified RBPs and screen the hub RBPs for pRCC prognosis. We identified 251 up-regulated and 129 down-regulated RBPs, and filtered out seven hub RBPs, namely, SRSF8, CD3EAP, HBS1L, ELAC2, MRPL34, NOP2 and IGF2BP2, for their prognostic relevance. A prognostic risk score model for overall survival of pRCC patients was constructed based on the seven hub RBPs. Further analysis showed that the low-risk group had higher survival rate than the high-risk group in both training and validation cohorts. The predictive accuracy was verified in the Human Protein Atlas database.In addition, we introduced the GSE15641 dataset from the Gene Expression Omnibus (GEO) database for independent external validation, and confirmed the expression levels of HBS1L, MRPL34 and IGF2BP2 through real-time quantitative PCR (RT-qPCR) and Western blotting (WB) using human renal tubular epithelial cell line HK-2 and human papillary renal cell carcinoma cell line Caki-2. In pRCC, CD3EAP was significantly elevated, while ELAC2, IGF2BP2, MRPL34, SRSF8 and HBS1L were significantly reduced. There was no significant difference between tumor and normal tissues in NOP2 expression. Risk score and tumor grade were independent prognostic factors associated with overall survival. In addition, we established a nomogram based on the seven prognostic RBPs to help predict overall survival at 1-3 years. In conclusion, seven differentially expressed hub RBPs were identified as potential prognostic biomarkers for pRCC. Our prognostic model might serve as a support for better treatment decision-making. Our work could provide potential new ideas for diagnosis and research on targeted drugs for pRCC.

Bioinformatics↗

PubMed2026

Stratifying lung adenocarcinoma: a novel prognostic model based on mitochondrial outer membrane permeabilization activity.

UNLABELLED: Mitochondrial outer membrane permeabilization (MOMP) is a core apoptotic regulatory event that dictates mitochondrial integrity, where full activation drives cell death and sublethal dysregulation contributes to tumor genomic instability. We used the Cancer Genome Atlas lung adenocarcinoma cohort (TCGA-LUAD) as the training cohort and the Gene Expression Omnibus dataset GSE42127 as the validation cohort to identify prognostic genes related to MOMP activity in lung adenocarcinoma (LUAD) and to evaluate their potential biological significance. By intersecting MOMP-related genes with differentially expressed genes, combined with survival analysis, Mendelian randomization analysis, and 101 machine-learning algorithm combinations, seven prognostic genes, namely BIRC5, PSMD11, TNFRSF13C, YWHAZ, YWHAG, CYCS, and LTB, were identified. Next, an optimal prognostic model was constructed based on the gradient boosting machine (GBM) algorithm. Based on the risk score, LUAD patients were stratified into high- and low-risk groups, and patients in the high-risk group exhibited poorer overall survival in both the training and validation cohorts. Furthermore, a nomogram integrating the risk score and clinicopathological factors was developed and showed favorable predictive performance for 1-, 3-, and 5-year survival. Meanwhile, functional and immune analyses revealed that the high-risk group was enriched in DNA replication-related pathways and demonstrated a higher tumor mutation burden (TMB). Correlation analysis indicated that TNFRSF13C was positively correlated with activated B cells, whereas BIRC5 was negatively correlated with eosinophils, suggesting that MOMP-related genes might be involved in remodeling the immune microenvironment of LUAD. Drug sensitivity analysis showed differences in predicted half-maximal inhibitory concentration (IC50) values between the risk groups, suggesting the potential value of this model in assisting therapeutic stratification. Single-cell RNA sequencing (scRNA-seq) further identified T lymphocytes as a key cell type, with numerous prognostic genes exhibiting differential expression in T cells or dynamic changes during differentiation. We suggest that the MOMP-related signature established in this study may provide a reference for prognostic stratification in LUAD and offers candidate prognostic genes for subsequent experimental and clinical validation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s13205-026-05058-6.

Lung adenocarcinoma↗

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 = 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 = 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

Prognostic significance of DNA damage response-related markers in esophageal squamous cell carcinoma using machine learning approaches.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) lacks reliable prognostic biomarkers. Homologous recombination deficiency (HRD) has been implicated in genomic instability across multiple cancers, but its prognostic significance in ESCC remains unexplored. This study aimed to evaluate HRD score as a prognostic biomarker and develop a machine learning-based predictive model for ESCC. METHODS: Transcriptomic and clinical data from 78 ESCC patients were obtained from The Cancer Genome Atlas (TCGA) and randomly split into training (70%) and test (30%) cohorts. Prognostic models were constructed using 112 machine learning algorithm combinations based on DNA damage response (DDR)-related genes. Gene set enrichment analysis (GSEA), somatic mutation profiling, and immune cell infiltration estimation via CIBERSORT were performed to characterize HRD-associated molecular features. RESULTS: High HRD scores were significantly associated with poorer overall survival (P<0.05). Among 112 algorithm combinations, the survival support vector machine (Survival-SVM) model demonstrated optimal performance [training concordance index (C-index): 0.741; test C-index: 0.708], identifying six hub genes: PARP1, MBD4, TELO2, NSMCE3, SMUG1, and BABAM1. A nomogram incorporating risk score (RS) and clinical variables achieved strong predictive accuracy for 1- to 3-year survival [area under the curve (AUC) >0.7]. High-HRD tumors exhibited distinct mutational patterns (TP53 and TTN) and enriched glutathione metabolism and cytochrome P450 pathways. Immune infiltration analysis revealed significant differences in plasma cell and neutrophil infiltration between risk groups (P<0.05), suggesting HRD-associated immune microenvironment remodeling. CONCLUSIONS: We developed a novel HRD-based prognostic model incorporating six DDR-related genes that demonstrates robust predictive performance in ESCC. HRD score is identified as an independent prognostic factor associated with genomic instability, immune microenvironment alterations, and clinical outcomes. These findings provide a theoretical basis for personalized treatment strategies, including potential applications of PARP inhibitors and immunotherapy in ESCC.

Esophageal squamous cell carcinoma (ESCC)↗

PubMed2026

Established and emerging prognostic factors in mycosis fungoides and Sézary syndrome.

Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL), characterized by heterogeneous clinical behavior and variable prognosis. Accurate prognostication is essential for risk-adapted management. This review synthesizes emerging evidence on prognostic factors in MF and SS, with a focus on recent genomic advances. Traditional prognostic frameworks are outlined, highlighting the prognostic impact of demographics, stage, clinical features, and histologic findings. More advanced prognostics are then outlined, including genomic alterations and impact of the tumor microenvironment. We highlight realms in which integration of traditional and more biological prognostic frameworks can support more individualized treatment strategies.

Sézary syndrome↗

PubMed1994

Survival superiority of females with melanoma. A multivariate analysis of 6383 patients exploring the significance of gender in prognostic outcome.

OBJECTIVE: To evaluate the effects of gender on prognostic outcome of patients with melanoma. DESIGN: Retrospective cohort study, including 20 years of follow-up. SETTING: Duke University Melanoma Clinic, Durham, NC, a referral center for patients with melanoma. PATIENTS: Patients with melanoma (N = 6383), consisting of 45% females and 55% males, obtained from a referred sample. Eligibility requirements were nonocular melanomas and white race. MAIN OUTCOME MEASURES: Time to metastases and survival. RESULTS: Females with melanoma demonstrated a superior prognostic outcome over males, with a 34% survival advantage and a 28% disease-free advantage. When each of the variables of age, site, Clark's level, histologic type, and tumor thickness was explored for possible influences on prognostic outcome, female survival advantage persisted, although modified by independent variables. The greatest influence came from the variables of site, Clark's level, and Breslow's thickness. Age, specifically in premenopausal vs postmenopausal age groups, was not significant in altering females' prognostic advantage. A multivariate analysis combining the effects of all the variables resulted in females still maintaining a 22% survival advantage and a 17% disease-free advantage. CONCLUSIONS: Females with melanoma have a significant prognostic advantage over their male counterparts that cannot be fully explained by influences from the variables of age, site, Clark's level, histology, and Breslow's thickness. This superior prognostic outcome does not appear to be associated with menstrual status. Evidence does suggest that the protective factor for females occurs at the level of metastases.

Adult↗