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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

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

[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

[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

[The importance of tumor angiogenesis as a prognostic indicator in primary breast cancer].

Recently, the importance of tumor angiogenesis in the process of tumor growth, progression and metastasis in solid tumors has been widely accepted. The prognostic value of angiogenesis has been demonstrated in a variety of solid tumors including breast cancer. In this report, we reviewed recent studies investigating on the value of intratumoral microvessel density (MVD), assessed by a sermiquantitative immunohistochemical assay with using factor-VIII related antibody or anti CD-31 antibody, as a prognostic indicator in primary breast cancer patients. Studies using factor-VIII related antibody showed that the average MVD ranged from 67.3 to 84.0 counts per mm2 area. When used by anti CD-31 monoclonal antibody, the average MVD were 120.3 approximately 135 counts per mm2 area in the range. More than 8 clinical investigations have showed that MVD was a potent prognostic indicator for relapse free survival and/or overall survival in both node-negative and -positive patients. Two reports concluded no prognostic value of MVD, however the average MVD of these two studies significantly differed from other reports. Thus, at present, angiogenesis grade seems to provide an independent prognostic value when the MVD was properly assessed. With respect to the relationship with conventional prognostic indicators, several reports showed the tendency that increased MVD was correlated with younger age and increase of tumor size below 3 cm diameter, however, some reports failed to demonstrate the tendency, suggesting that these correlations are still in controversial. Biological markers including ER, p53 and c-erB2 showed no correlation with the MVD in many studies including our investigation. Only a significant correlation we found was that MVD was increased in tumors with the expression of vascular endothelial growth factor and platelet-derived endothelial cell growth factor, which are noted to be potent endothelial growth factor. Since the evaluation of tumor angiogenesis as a prognostic indicator is now widely investigated in a prospective study, MVD might be introduced to the category of the criteria for determining the schedule of postoperative adjuvant therapy of breast cancer.

Age Factors

Age-related prognostic factor analysis in non-Hodgkin's lymphoma.

BACKGROUND: Age is known to have an important influence on survival in non-Hodgkin's lymphoma (NHL). This observation and the relationship of age to other prognostic factors are of interest in designing treatment programs for these patients. This study was conducted to investigate the relationship of age to other known prognostic variables and survival in NHL. PATIENTS AND METHODS: Data on clinical features, treatment, response, survival and cause of death from 547 patients with NHL diagnosed between 1980 and 1989 were collected and analyzed by age group. Multivariate analysis of prognostic factors and a survival comparison to an age and sex matched control population were performed. RESULTS: Survival curves for 5-year age groups up to and including age 60-64 years were similar, after which a major effect of age upon survival was apparent. When groups aged < 65 years and > and = 65 years were compared, there were similar proportions of most known prognostic factors, except for a higher proportion with increased lactate dehydrogenase (LDH) levels and extranodal disease in older patients. When analyzed by age group, older patients had a lower response rate to initial therapy and salvage treatments. In younger patients, several recognized prognostic variables were found to lack significance. CONCLUSIONS: Prognostic variables differ between younger and older patients with NHL. Age, histology, LDH elevation and gender are less important in younger patients; only bulky disease is more important than in older patients. A lower response rate, poor response to salvage therapy and excess mortality, often due to concurrent diseases, were apparent in older patients. Age is a significant prognostic factor only in patients age > and = 65 years.

Age Factors

[Identification and validation of prognostic factors in differentiated thyroid carcinoma].

BACKGROUND: The aims of this study are to identify prognostic factors of differentiated thyroid carcinoma and to validate the application of prognostic classifications obtained by others studies to another population. PATIENTS AND METHODS: The survival of 208 patients with differentiated thyroid carcinoma (129 papillary and 79 follicular carcinoma) was calculated by the Kaplan-Meier method. The mean follow-up was 7.5 years (1-17.7). Cox-proportional hazard model was used for variables influencing on survival (Mantel-Cox method). In addition, the EORTC, AGES, AJC, AMES and DeGroot classifications were tested. RESULTS: The independent prognostic factors identified were patient age > 60 years, tumor size > 6 cm and the presence of distant metastases. The absence of poor prognostic factors defined the low risk group (153 patients, survival 97% at 17.7 years of follow-up). The application of the other prognostic classifications differentiated several risk groups not in accordance with those obtained in the initial population. CONCLUSIONS: In this series of patients with thyroid carcinoma the main prognostic factors were age, tumor size and the presence of distant metastases. However, there are pitfalls in applying the prognostic classifications of published studies to another population.

Adenocarcinoma, Follicular

Prognostic value of DNA ploidy using flow cytometry in 1301 breast cancer patients: results of the prospective Multicenter Morphometric Mammary Carcinoma Project.

The literature on breast cancer reports conflicting prognostic results with respect to DNA ploidy of flow cytometric DNA histograms. This might result from different DNA ploidy classification methods. Our study evaluated the prognostic power of DNA ploidy, using different classification methods, in a large prospective group (n = 1301) of breast cancer patients. Flow cytometric DNA histograms obtained from fresh frozen material were interpreted with use of a commercially available computer program. On the basis of the number of stemlines and the DNA Index, we classified the DNA ploidy by different methods. In all of the cases, the classification method "DNA diploid versus DNA nondiploid" provided the best prognostic significance for overall survival (OS) (Mantel-Cox (MC) = 5.4, P = .02; relative risk (RR) = 1.3, P = .05) and for disease-free survival (DFS) (MC = 11.8, P = .0006; RR = 1.3, P < .05). This was also true for the OS of the lymph node-positive (but not the lymph node-negative) subgroup (MC = 4.1, P = .04; RR = 1.3, P = .05). In subgroups classified on the basis of tumor size, DNA ploidy showed prognostic significance for DFS only in the subgroup of tumors smaller than 2 cm and larger than 5 cm. In multivariate analysis, DNA ploidy showed no additional prognostic power to lymph node status and tumor size. The classification "DNA diploid versus DNA nondiploid" was mostly consistent with respect to prognostic power for OS and DFS, especially in small or lymph node-positive tumors. The RR of DNA nondiploid patients was only marginally higher, however, so large study groups are required to reach statistical significance. This could partly explain the disagreements in the literature. Therefore, DNA ploidy seems to be of little clinical importance in breast cancer patients, compared with other prognostic parameters.

Adult

Prognosis of patients with advanced Hodgkin's disease: evaluation of four prognostic models using 344 patients included in the Group d'Etudes des Lymphomes de l'Adulte Study.

BACKGROUND: To determine whether a high risk group could be identified within a group of patients with advanced stage Hodgkin's disease (HD), the authors applied several prognostic models to patients treated according to the H89 protocol. METHODS: This study included 344 patients with Stage IIIB-IV HD who were treated with chemotherapy alone (8 cycles) or chemotherapy (6 cycles) plus radiation therapy. Four prognostic models were selected for this study: the numeric prognostic index of the Scotland and Newcastle Lymphoma Group, the Christie Hospital (Manchester)-St. Bartholomew's Hospital (London) model, the Memorial Sloan-Kettering Cancer Center (MSKCC) model, and the criteria used in the European Bone Marrow Transplant (EBMT)/Intergroup Trial. RESULTS: Univariate analysis of H89 protocol patients showed that 5 variables included in the models had prognostic significance: age > 45 years (P = 0.0001), anemia (hemoglobin < 12 g/dL for males and < 10 g/dL for females) (P = 0.0001), number of extranodal sites > or = 2 (P = 0.0013), serum lactic acid dehydrogenase greater than the normal value (P = 0.0018), and lymphocyte count < 0.75 x 10(9) L(-1) (P = 0.0063). All four models divided patients into prognostic subgroups. Significant differences among the subgroups were found by log rank analysis (chi-square test = 11-48; P = 0.01-0.0001). The worst prognostic group defined by the MSKCC model (> or = 3 adverse factors) had an overall survival rate of 59% at 3 years and an estimated 3-year event free survival rate of 43%. CONCLUSIONS: Patients with at least three adverse factors according to the MSKCC model or the EBMT criteria had a higher risk of failure with conventional treatment; however, based on survival rate, no very high risk group could be identified. Nonetheless, these prognostic models may be useful to recognize patients with good prognosis who can be cured with conventional therapy and for whom treatment morbidity and mortality can be minimized.

Adult

[Evolution and prognostic factors of adenocarcinomas of the prostate metastasizing at diagnosis].

OBJECTIVES: In 30-40% patients, prostate adenocarcinoma is diagnosed already in the metastatic phase, a percentage that will depend on the number of patients with localized cancer that we are unable to detect. Hormonal suppression is the most widely accepted therapeutical option, although there are doubts on the value of rescue treatment after the hormone-refractive stage. This paper analyses those parameters as well as the main prognostic factors in a series of 135 patients with metastatic prostate cancer at diagnosis. MATERIAL AND METHODS: Between 1983 and 1996, 414 patients were diagnosed with prostate adenocarcinoma in the Urology Unit. Móstoles Hospital, 135 of which (32.6%) were metastatic at the time of diagnosis and were managed as follows: 113 (84%) were treated with maximum androgenic blockade (MAB). 13 (9.6%) with orchiectomy and antiandrogens, 5 (3.7%) with various treatments, and only 4 received symptomatic treatment. Of those treated with MAB, 97 (72%) continued treatment after the hormone-refractive stage and 16 (12%) were given stramustine phosphate instead of the antiandrogen. Response monitoring was done basically by means of serial PSA determination. The parameters analyzed included survival and the following potential prognostic factors: age, performance status, metastatic bone pain, tumour diagnosis based on number of metastasis, prior PSA level, Gleason, local stage, M1 type at diagnosis based on the 1992 TNM classification, and response to the various treatment applied. RESULTS: Mean age: 72 years. Over an average of 25 (0-127) months, 80 (59%) patients have died; mean follow-up of patients alive at end of study: 24 months (3-111). Lost to follow-up: 6 patients (4.4%). Up to 1991, the proportion of patients with metastasis was 48%; since 1992, 24%. Percentage of patients diagnosed due to clinical manifestations of the metastasis (25 patients) over these two periods increased, mean age decreased and the proportion of patients with highly aggressive tumours increased. Mean overall survival, 26 months: influential prognostic factors: diagnosis due to metastasis and Gleason greater than 7; very poor prognosis for those receiving no hormonal therapy, with no differences between drug versus surgical treatment. Tumour-dependent mean survival, 32 months; influential prognostic factors: performance status, metastatic bone pain, diagnosis due to metastasis and Gleason greater than 7; very poor prognosis for those receiving no hormonal therapy. Progression-free interval, 19 months; influential prognostic factors: metastatic bone pain, PSA higher or lower than 90. Gleason greater than 7 and local stage: no differences between treatments. Mean survival after progression, 6 months; influential prognostic factors: diagnosis due to metastasis, M1b versus M1c patients: increased survival in patients rescued with stramustine phosphate. CONCLUSIONS: The proportion of prostate adenocarcinomas with metastasis at diagnosis shows a trend to decrease, although the percentage of patients who are diagnosed by the sings and symptoms of their metastasis is increasing. These patients should be treated with pharmacological or surgical hormone-suppression. Rescue treatment with stramustine phosphate prolongs survival. Influential prognostic factors: Gleason greater than 7, metastatic bone pain, tumour extent and previous PSA.

Adenocarcinoma

Prognostic factors in uterine carcinosarcoma: a clinicopathologic study of 25 patients.

BACKGROUND: Carcinosarcoma (malignant mixed mullerian tumor) of the female genital tract is a highly malignant neoplasm. The tumor stage and histologic grade of the carcinomatous component are among the important prognostic indicators cited in the literature for this tumor. METHODS: Twenty-five patients with uterine carcinosarcoma at 4 hospitals in the Kyoto and Nara areas of Japan were studied retrospectively. The clinicopathologic and immunohistochemical data including p53, bcl-2, Ki-67, and proliferating cell nuclear antigen (PCNA) staining were analyzed using univariate and multivariate analysis with the Cox proportional hazards model to investigate potential prognostic indicators for this neoplasm. RESULTS: The 5-year survival rate was 36.4% for all stages, 62.3% for Stage I, and 0% for Stages II-IV. From the univariate analysis, stage (P = 0.0001), endometrioid adenocarcinoma as a carcinomatous component (P = 0.0006), age (P = 0.0355), and a heterologous sarcomatous component (P = 0.0421) were found to be prognostically significant for patient survival. Stage was the only independent significant factor in the multivariate analysis (t = 2.212). None of the other factors (history of pregnancy and gestation, gross appearance of the tumors, grade of the carcinomatous component, mitotic count of the sarcomatous component, Ki-67 and PCNA reactivity, or p53 or bcl-2 positive staining) was found to be a significant prognostic indicator. CONCLUSIONS: Stage appears to be the only definite independent prognostic indicator of survival in patients with uterine carcinosarcoma. It is uncertain whether age, endometrioid adenocarcinoma as a carcinomatous component, or absence of a heterologous component in the sarcomatous area are prognostic factors. Immunohistochemical expression of p53, bcl-2, Ki-67, or PCNA is not a prognostic indicator. The immunohistochemical results of the current study may support the hypothesis of a common stem cell origin of this tumor.

Adult

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

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

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

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)

Established and emerging prognostic factors in mycosis fungoides and S&#xe9;zary syndrome.

Mycosis fungoides (MF) and S&#xe9;zary 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.

S&#xe9;zary syndrome

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

Microvessel density is a prognostic indicator for patients with astroglial brain tumors.

BACKGROUND: Microvessel density in tumors, a measure of angiogenesis, has been shown to be a prognostic indicator that correlates with an increased risk of metastasis in various epithelial cancers and with overall and relapse free survival in patients with breast cancer. Astrocytic brain tumors, particularly malignant astrocytomas, are recognized to be highly vascular tumors with potent angiogenic activity. However, the prognostic significance of microvessel density in these tumors is not known. METHODS: Sections from formalin fixed paraffin embedded tumor tissue from 93 unselected adult patients with supratentorial astrocytic brain tumors were immunostained for factor VIII-related antigen in order to highlight microvessel endothelial cells. Microvessels were counted at 200x and 400x magnification. Microvessel density was graded as 1+ to 4+ on 1 low power field, without knowledge of clinical outcome. Microvessel count and microvessel grade were correlated with postoperative survival using the Cox proportional hazards regression model. The prognostic significance of microvessel count and grade were also compared with established prognostic indicators, including patient age, Karnofsky performance status, and tumor histology using multivariate analyses. RESULTS: Both microvessel grade and microvessel count correlated significantly with postoperative survival by univariate analysis in both previously untreated and treated patients. Patients with tumors containing a microvessel Grade of 3+ or 4+ had significantly shorter survival time than patients with a microvessel Grade of 1+ or 2+ (P = 0.0022). Likewise, patients with microvessel counts of 70 or greater had significantly shorter survival than those with microvessel counts of fewer than 70 (P = 0.041). Patient age, Karnofsky performance status, tumor histology, and extent of resection were also correlated with survival by univariate analysis. Microvessel count was further shown to be an independent prognostic indicator by multivariate analyses. There were correlations between microvessel density and patient age and between microvessel density and astrocytic tumor grade. CONCLUSIONS: These findings support the importance of microvessel density as a prognostic indicator of postoperative survival of patients with astroglial brain tumors. Regional tumor heterogeneity may limit the use of these techniques for routine pathologic examination.

Adult