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At least 127 records · Page 7Linked to original sources

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↗

PubMed1996

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↗

PubMed1996

Analysis of prognostic factors after the first relapse of Hodgkin's disease in 187 patients.

BACKGROUND: Patients in the first relapse of Hodgkin's disease comprise a heterogeneous group regarding their primary treatment and their clinical characteristics. Because therapeutic options for these patients vary from radiotherapy to combined modality or high dose therapy, we wanted to identify the prognostic factors that would optimize the treatment choice among the different options available. METHODS: Patients (n = 187) who relapsed for the first time after the end of treatment were included. Characteristics at diagnosis were: male to female ratio: 1.5; Stage III and IV: 59%; B symptoms: 60%; and mediastinal involvement: 76%, bulky in 29%. Chemotherapy (27%) or combined modality (73%) was prescribed. Relapses occurred 3 to 192 months (median: 35 mos) after the end of treatment; for 39% this interval was < 12 months. Characteristics at relapse were: Stage III and IV: 59%; and B symptoms: 46%. At first relapse, treatment was conventional (chemo- and/or radiotherapy) in 44% and intensive (high dose therapy with stem-cell transplantation) in 56%. These regimens led to 85% complete responses; and 15% were refractory. RESULTS: The median follow-up after relapse was 31 months and the median time to second progression was 20 months. The median freedom from second failure (FF2F) was 44 months and the median survival was 72 months. All factors were analyzed for survival and FF2F. Patients given intensive treatment had more adverse prognostic factors at relapse (B symptoms, early relapse, and disseminated relapse). Multivariate analysis identified 2 significant prognostic factors: interval end of treatment-relapse < 12 months (< 10(-4)) and Stage III and IV at relapse (P = 0.0013). For patients with at least one adverse prognostic factor, high dose therapy gave the best survival results. CONCLUSIONS: Using 2 simple prognostic factors, (interval end of treatment-relapse < 12 months and Stage III/IV at relapse), patients in first relapse of Hodgkin's disease can be classified into 3 significant prognostic groups in terms of survival and FF2F.

Adolescent↗

PubMed1989

Prognostic factors in inflammatory breast cancer. Univariate and multivariate analysis.

Between 1958 and 1985, 107 patients with nonmetastatic inflammatory breast cancer (IBC) received radiotherapy as all or part of initial treatment at the Mallinckrodt Institute of Radiology. For this review, the diagnosis of IBC was made on the basis of either clinical or histopathologic criteria. Fifteen factors of potential prognostic significance were evaluated, by both univariate and multivariate analysis. For relapse-free survival, univariate analysis suggested prognostic value for initial tumor size, discrete versus diffuse tumor mass, adjuvant chemotherapy, and mastectomy. In the multivariate analysis, the independent prognostic factors, in order of significance, were mastectomy, diffuse versus discrete tumor mass, and race (marginal). For survival, univariate analysis suggested prognostic value for initial tumor size, diffuse versus discrete tumor mass, nodal stage, year of treatment, adjuvant chemotherapy, and mastectomy. In the multivariate analysis, the prognostic factors in order of significance were mastectomy and chemotherapy (marginal). The diagnostic selection group showed no prognostic value, suggesting that either clinical or histopathologic criteria justify the diagnosis of IBC. Our results appear to support a role for surgery as part of the combined modality approach to this disease.

Adult↗

PubMed1992

DNA level and stereologic estimates of nuclear volume in squamous cell carcinomas of the uterine cervix. A comparative study with analysis of prognostic impact.

Grading of malignancy in squamous cell carcinomas of the uterine cervix is based on qualitative, morphologic examination and suffers from poor reproducibility. Using modern stereology, unbiased estimates of the three-dimensional, volume-weighted mean nuclear volume (nuclear vv), were obtained in pretreatment biopsies from 51 patients treated for cervical cancer in clinical Stages I through III (mean age of 56 years, follow-up period greater than 5 years). In addition, conventional, two-dimensional morphometric estimates of nuclear and mitotic features were obtained. DNA indices (DI) were estimated by flow cytometry. Finally, the semiquantitative malignancy grade score value (MGS) was determined according to previously published methods. Estimates of nuclear vv were on average increased in euploid lesions (2P = 0.01), but the overall relationship between nuclear vv and DI was poor. Different clinical stages of disease did not differ with regard to nuclear vv (2P = 0.99) and DI (2P = 0.56). No relationship was disclosed between MGS and nuclear vv (2P = 0.85). Single-factor analysis showed prognostic impact of clinical stage of disease (2P = 0.0001) and DI (2P = 0.04), whereas estimates of nuclear vv were only of marginal prognostic significance (2P = 0.07). However, Cox multivariate regression analysis showed independent prognostic value of patient age and nuclear vv along with clinical stage and DI. All other investigated variables were rejected from the model. A prognostic index with highly distinguishing capacity between prognostically poor and favorable cases was constructed (2P = 1.9 x 10(-7)). It is concluded that realistic estimates of nuclear volume are independent of nuclear DNA content and are of prognostic value for objective malignancy grading in patients with squamous cell carcinoma of the uterine cervix.

Adult↗

PubMed1992

The future of prognostic factors in outcome prediction for patients with cancer.

The anatomic description of the extent of tumor spread (tumor staging) assists clinical management, facilitates communication among physicians, is an essential part of randomized controlled trials, and may help in the counseling patients and their families. However, in recent years, additional "prognostic factors" have been defined, many of which assess or reflect the biologic behavior of malignant neoplasms. Other measures of tumor biochemistry address the natural history of neoplastic development and often are included in a discussion of new prognostic factors. This review article summarizes current knowledge and thinking related to tumor prognostic factors in four areas by providing: (1) a definition and principles of anatomic spread of tumor (staging) and some suggestions for improvement, (2) a description of some examples of additional factors of prognostic significance, (3) some statistical methods to evaluate prognostic factors, and (4) an examination of the possible future of summary statements of outcome (i.e., prognostic indexes).

Biomarkers↗

PubMed1993

A prospective study of the prognostic value of cathepsin D levels in breast cancer cytosol.

BACKGROUND: Cathepsin D is a lysosomal protease overexpressed and abnormally secreted in most breast cancer cells. Several retrospective clinical studies have shown that cathepsin D is an independent prognostic factor in breast cancer that is associated with a higher risk of recurrence and a shorter overall survival. METHODS: To the authors' knowledge, this is the first prospective study in which the prognostic value of cathepsin D was studied in 123 patients with primary breast cancer who were followed for 5 years between March 1985 and December 1990. Cathepsin D concentrations in breast cancer cytosol were measured using a solid-phase sandwich immunoenzymatic assay. The most significant prognostic factors were identified by multivariate analysis using the Cox proportional-hazards method. RESULTS: The median value of cathepsin D was 20.8 pmol/mg of protein, which was approximately half than the median value found in subsequent assays done using a commercially available kit and reported in most retrospective studies. The cathepsin D status or level was correlated only with axillary lymph node involvement. A univariate analysis showed that high levels of cathepsin D (> 20 pmol/mg of protein) were correlated with a higher risk of recurrence and a shorter overall survival (P < 0.01 and P < 0.03, respectively). Using multivariate analysis, a high cathepsin D level, a negative progesterone receptor status, and lymph node involvement were the most important factors for predicting relapse-free survival (P = 0.02, P < 0.01, and P < 0.05, respectively). The cathepsin D level had prognostic value in patients with node-positive disease (P = 0.001) and appeared to be particularly useful in association with the progesterone receptor status by isolating a high-risk subgroup of patients (high cathepsin D level; negative progesterone receptor status). CONCLUSIONS: This first prospective study confirmed the prognostic value of the cathepsin D level in association with other major prognostic factors. The next step will be to determine whether the subset of patients with high cathepsin D levels would benefit from adjuvant therapy.

Adult↗

PubMed1993

Prognostic factors in stage D2 prostate cancer treated with a pure nonsteroidal antiandrogen.

BACKGROUND: Prognostic factors have been shown to be important when stratifying patients with prostate cancer into randomized trials and counseling the individual patient regarding his chances of response to treatment. However, there are no reports on prognostic factors in patients with Stage D2 prostate cancer treated with a pure antiandrogen as monotherapy. METHODS: The authors studied a variety of possible prognostic factors among 150 patients with metastatic prostate cancer treated with an antiandrogen (Casodex, Imperial Chemical Industries, Wilmington, DE). RESULTS: In a univariate analysis, performance status; extent of disease (EOD); pretreatment hemoglobin, alkaline phosphatase, prostate-specific antigen (PSA), and prostatic acid phosphatase (PAP) levels; and extent of disease (EOD) on bone scan all were found to be significant prognostic factors (P < 0.05). Pretreatment serum testosterone levels, identified as one of the most important prognostic factors, was not identified as significant in the current study. CONCLUSIONS: Although the pretreatment testosterone level was shown to be an important prognostic factor in previous studies, using other modes of androgen ablation (reducing testosterone to below castrate levels), the current study suggest it may not be a helpful factor if the therapy used is antiandrogens as monotherapy. This may relate to the different mode of action of antiandrogens, which do not reduce serum testosterone levels.

Androgen Antagonists↗

PubMed1993

Prognostic, quantitative histopathologic variables in lobular carcinoma of the breast.

BACKGROUND: A retrospective investigation of 53 consecutively treated patients with operable lobular carcinoma of the breast, with a median follow-up of 6.6 years, was performed to examine the prognostic value of quantitative histopathologic parameters. METHODS: The measurements were performed in routinely processed histologic sections using a simple, unbiased technique for the estimation of the three-dimensional mean nuclear volume (vv(nuc)). In addition, quantitative estimates were obtained of the mitotic index (MI), the nuclear index (NI), the nuclear volume fraction (Vv(nuc/tis)), and the mean nuclear profile area (aH(nuc)). RESULTS: Estimates of vv(nuc), MI, NI, and Vv(nuc/tis) were of significant or marginally significant prognostic value in univariate analyses, whereas no prognostic significance was attributed to estimates of aH(nuc). In multivariate Cox analyses, the clinical stage of disease, vv(nuc), MI, and NI were of significant independent, prognostic value. On the basis of the multivariate analyses, a prognostic index with highly distinguishing capacity between prognostically poor and favorable cases was constructed. CONCLUSION: Quantitative histopathologic variables are of value for objective grading of malignancy in lobular carcinomas. The new parameter--estimates of the mean nuclear volume--is highly reproducible and suitable for routine use. However, larger and prospective studies are needed to establish the true value of the quantitative histopathologic variables in the clinical management of patients with breast cancer.

Adult↗

PubMed1994

Intermediate-grade lymphomas treated with cyclophosphamide-doxorubicin- vincristine-prednisone-bleomycin alternated with cyclophosphamide-methotrexate-etoposide-dexamethasone. Application of prognostic models to data analysis.

BACKGROUND: Numerous treatment strategies have been tried with the aim of improving results for patients with intermediate-grade lymphomas (IGL) over those achieved with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo), and numerous prognostic models have been developed to identify and separate risk groups. This study reports on a new protocol for Ann Arbor Stages II-IV IGL that consists of CHOP-Bleo alternated with a new regimen of cyclophosphamide, methotrexate, etoposide, and dexamethasone (CMED) and radiation therapy and demonstrates the usefulness of prognostic models for identifying risk groups and comparing treatment programs. METHODS: One hundred seventy patients with Ann Arbor Stages II-IV IGL were treated with alternating cycles of CHOP-Bleo and CMED for a total of 12 cycles. Involved field radiation therapy was interspersed with courses of chemotherapy for patients with Stage II and Stage III disease. Results were analyzed and compared with those of the authors' previous study of CHOP-Bleo and radiation therapy using the Ann Arbor staging system, their earlier prognostic model, and the recently published International Index. RESULTS: A complete remission occurred in 78% of the patients. The overall 5-year survival rate was 67%. Survival was better for patients with Ann Arbor Stage II disease (80%) than for those with Stage III or Stage IV (67% and 58%, respectively). High tumor burden, above-normal levels of serum lactic dehydrogenase, serum beta 2-microglobulin, and Ann Arbor Stage IV disease were adverse factors. The International Index and the authors' earlier prognostic model separated four prognostic groups. CHOP-Bleo/CMED was generally well tolerated. Neutropenic fever was the major complication that occurred in 25 patients during treatment. Six of these patients died of sepsis. CONCLUSIONS: This study demonstrated that CHOP-Bleo/CMED is a well-tolerated regimen that produced better results than those reported for a former study that used CHOP-Bleo alone. Further, results for CHOP-Bleo/CMED compared favorably with those of other second- and third-generation regimens. The study also validated the usefulness of prognostic models and, in particular, the new International Index for identifying risk groups.

Adolescent↗

PubMed1995

Advanced diffuse non-Hodgkin's lymphoma. Analysis of prognostic factors by the international index and by lactic dehydrogenase in an intergroup study.

BACKGROUND: Recent data have suggested that there are no differences among various anthracycline-based chemotherapy regimens [including cyclophosphamide, vincristine, methotrexate, and prednisone (CHOP), methotrexate, calcium leucovorin, bleomycin, doxorubicin, cyclophosphamide, and dexamethasone (m-BACOD), methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B), and cyclophosphamide, doxorubicin, etoposide, prednisone, cytosine arabinoside, bleomycin, vincristine, methotrexate, and calcium leucovorin (PROMACE-cyta-BOM)] in patients with diffuse aggressive lymphomas. Because outcome appears to depend on certain prognostic factors, risk groups can be identified. Therefore, these prognostic factors were examined for their correlations with survival, time-to-treatment failure (TTF), and disease free survival (DFS) in a group of patients with diffuse aggressive non-Hodgkin's lymphoma who were treated on a single randomized trial with either CHOP or m-BACOD. METHODS: From July 1984 to January 1988, 392 patients with diffuse large cell or diffuse mixed non-Hodgkin's lymphoma were enrolled in an Intergroup study and were randomly assigned to treatment with CHOP or m-BACOD chemotherapy. Of these, 325 were eligible for response, toxicity, and survival analysis, and the results were reported. The survival and TTF results now have been updated. The 286 patients who had lactic dehydrogenase (LDH) data available at study entry were analyzed for prognostic features according to the International Index criteria and using Martingale Residuals for proportional hazards regression. RESULTS: There were no differences in survival, TTF, and disease free survival between groups of patients treated with either CHOP or m-BACOD. In addition, analysis using the International Index criteria confirmed that patients in the lower risk groups had better outcome than patients in the higher risk groups (5-year survival was 56 and 58% for low and low/intermediate risk groups, respectively, and 37% and 31% for high/intermediate and high risk groups, respectively). There were, however, no differences in survival, disease free survival, or TTF within any risk group when treatment with CHOP or m-BACOD were compared. In addition, analysis using Martingale residuals for proportional hazards regression identified LDH level (> 3 x normal) as an important prognostic factor that was not captured by the International Index. Thus, 5-year survival was 57% if LDH was normal or below, 42% if LDH was 1-3 x normal, and 21% if LDH was > 3 x normal. CONCLUSION: In patients with advanced diffuse large cell or diffuse mixed non-Hodgkin's lymphoma, there are no differences in outcome that can be attributed to treatment with CHOP vs. m-BACOD; this holds for any prognostic group identified by the International Index. However, the level of LDH at time of study entry is an important prognostic factor that is predictive of survival and may help to identify candidates for future clinical trials.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

Prognostic implication of the p53 protein and Ki-67 antigen immunohistochemistry in malignant fibrous histiocytoma.

BACKGROUND: Mounting evidence indicates that p53 regulates cell growth and abnormal p53 immunophenotypic expression is associated with an unfavorable prognosis for patients with some types of carcinoma. The prognostic significance of p53 overexpression in malignant fibrous histiocytomas (MFHs) of soft tissue has not yet been elucidated. METHODS: Expressions of p53 protein and Ki-67 antigen in 54 primary MFHs of soft tissue were investigated immunohistochemically and indexed quantitatively by counting the number of immunoreactive nuclei versus the total neoplastic nuclei in the representative fields of each tumor to evaluate their prognostic implications and interrelations with other clinicopathologic parameters. RESULTS: The percentages (labeling indices [LIs]) of p53 and Ki-67-immunoreactive nuclei versus the total neoplastic nuclei were 0.1-93.2% (mean +/- standard deviation [SD], 40.6% +/- 21.8%) and 5.3-90.8% (mean +/- SD, 42.7% +/- 29.4%), respectively. The Ki-67 LI correlated with histologic grade (P = 0.01498), primary tumor size (P = 0.04985), disease free interval (reverse correlation, P = 0.00776), and recurrence and metastasis (P = 0.00360). The p53 LI correlated with primary tumor size (P = 0.00431) but did not show any significant correlation with histologic grade, Ki-67 LI, primary tumor size, disease free interval, or recurrence and metastasis. Other significant correlations included histologic grade and disease free interval (P = 0.00010), primary tumor size and disease free interval (reverse correlation, P = 0.00869), histologic grade and recurrence (P = 0.02714), and primary tumor size and primary tumor location (P = 0.00028). In the grouped survival analysis, patients with recurrence or metastasis or with tumors of larger size (> or = 7 cm), high histologic grade, or higher Ki-67 LI (> or = 25%) had a significantly reduced survival (P < 0.05). The different p53 immunohistochemical expression and the different histologic types did not reflect different cumulative survival (P > 0.05). Regression analysis revealed that the primary tumor size and histologic grade, but not Ki-67 or p53 LIs, were independent statistical variables for prognostication. CONCLUSIONS: These results indicate that (1) primary tumor size and histologic grade are two important prognostic factors, (2) Ki-67 LI should be used in adjunct with other main prognostic factors for patients with MFHs, and (3) nuclear p53 overexpression in MFHs of soft tissue is a comparatively common event that has no prognostic implication.

Adult↗

PubMed1995

Flow cytometric DNA analysis and lysosomal cathepsins B and L in locally advanced laryngeal cancer. Relationship with clinicopathologic parameters and prognostic significance.

BACKGROUND: The traditional factors of locally advanced laryngeal squamous cell carcinoma (LSCC) have limited predictive value for the identification of high risk patients. Therefore, it is extremely important to define prognostic factors that identify the more aggressive types. Reliable and reproducible prognostic indicators are being investigated to help clinicians identify high risk groups and address more rational treatment. METHODS: Flow cytometric DNA ploidy and S-phase fraction (SPF) measurements were performed on frozen tumor tissues from a consecutive series of 71 patients with Stage III and IV LSCC: Lysosomal cathepsin B and L activity levels were determined biochemically in matched paired sets of tumor tissue and normal mucosa samples. RESULTS: By univariate analysis, lymph node positivity, poor histologic differentiation, DNA aneuploidy, high SPF, and high tumor/mucosa ratio of cathepsin B activity were significantly related to risk of relapse, whereas only DNA aneuploidy and high SPF proved to be significantly related to risk of death. Multivariate analysis showed that high histologic grade and high SPF values (> 15.1%) were independent prognostic factors related to risk of relapse (relative risk [RR] = 3.54; 95% confidence limits [CL] = 1.05-12.0; and RR = 4.22; CL = 1.54-11.6, respectively), whereas only high SPF was related to risk of death (RR = 3.63; CL = 1.17-11.3). CONCLUSIONS: S-phase fraction is an independent predictor of relapse free and overall survival in patients with locally advanced LSCC. On the basis of these findings, SPF should be used in addition to other established prognostic factors to refine the prognostic assessment of these patients further. More studies are needed for a better evaluation of the prognostic significance of DNA ploidy and that of lysosomal cysteine proteinases in these tumors.

Adult↗

PubMed2026

Comprehensive In Silico Analysis Identifies MSTO1 and LIG1 as Candidate Biomarkers With Diagnostic and Prognostic Relevance in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and remains a major cause of cancer-related mortality worldwide. Its poor clinical outcomes are largely attributed to late-stage diagnosis and the limited accuracy of currently available diagnostic and prognostic biomarkers. Therefore, identifying novel molecular markers with improved sensitivity, specificity, and therapeutic relevance is essential for enhancing early detection and guiding personalized treatment strategies. AIMS: To identify and prioritize novel candidate HCC biomarkers with diagnostic and prognostic value and potential therapeutic vulnerability using integrated multi-omics, survival, functional dependency, and tumor microenvironment analyses. METHODS AND RESULTS: We examined the mRNA and protein expression levels of 8 DEGs in HCC tissues in the TCGA and CPTAC datasets using UALCAN, which showed that MSTO1 and LIG1 were overexpressed consistently in HCC relative to normal liver tissues. Moreover, elevated expression levels of these genes were significantly associated with higher tumor grade and advanced stage. Kaplan-Meier plotter survival data confirmed that increased expression of MSTO1 and LIG1 was associated with poorer overall survival. The DepMap CRISPR knockout data confirmed a functional dependency of both genes in HCC cell lines. CBioPortal analyses provided characterization of genomic alterations and enabled enrichment analysis of co-expressed genes, and the TCGA-UALCAN pan-cancer analyses supported the assessment of tissue specificity across tumor types. TIMER3 analyses linked candidate gene expression with immune cell infiltration patterns. Diagnostic performance by ROC analysis showed excellent discrimination for MSTO1 (AUC = 0.987) and good discrimination for LIG1 (AUC = 0.897). Multivariate Cox regression with Benjamini-Hochberg FDR correction across the eight genes supported MSTO1 as a candidate independent prognostic factor after adjustment for tumor stage, grade, etiology, age, and sex (HR = 1.29, p = 0.035), whilst LIG1 showed no independent prognostic value. Promoter methylation of MSTO1 and ADH4, assessed via UALCAN, showed that both genes were significantly differentially methylated in the promoter region of primary HCC tissues compared with normal liver tissues. Our study also confirmed the biological and clinical relevance of established HCC biomarkers: TERT, IRAK1, and ADH4. CONCLUSION: MSTO1 and LIG1 emerged as candidate diagnostic biomarkers in HCC. Additionally, MSTO1 showed a candidate prognostic association with overall survival that remained significant after adjusting for tumor stage, grade, and etiology, as well as patients' age, but not after further adjustment for AFP status. Functional data also highlighted MSTO1 as a candidate therapeutic dependency. On the other hand, LIG1 showed no independent prognostic association in either multivariate model. Their differential expression and functional essentiality in HCC cell lines highlighted their value for further experimental and independent-cohort validation before potential integration into biomarker development pipelines aimed at improving early detection and targeted therapy in HCC.

Humans↗

PubMedDate not supplied

Prognostic value of serum fibronectin concentration in alcoholic cirrhotic patients.

The aim of this study was to assess prospectively the prognostic value of serum fibronectin in 114 alcoholic cirrhotic patients and to compare serum fibronectin with other prognostic variables. The Cox model and log-rank test were used to compare survival rates at 1 year. Considered alone, serum fibronectin, age, serum albumin, total serum bilirubin, gamma-glutamyl transpeptidase, prothrombin time, presence of encephalopathy and ascites were associated with survival to 1 year. The estimated survival rate at the end of 1 year was, for patients with serum fibronectin greater than 165 mg per liter: 84 +/- 5%, and for patients with serum fibronectin less than or equal to 165 mg per liter: 53 +/- 7% (p less than 0.001). With the step-wise multidimensional analysis using the Cox model to assess the combined effect of several prognostic variables, serum fibronectin was the first variable selected followed by age, encephalopathy and serum albumin which entered the model by virtue of their independent prognostic value. Multivariate regression and partial correlation analysis showed that fibronectin was independently correlated with serum albumin, gamma-glutamyl transpeptidase and total serum bilirubin explaining that the prognostic value of albumin diminished and that the prognostic value of total serum bilirubin and gamma-glutamyl transpeptidase disappeared when combined with serum fibronectin.

Bilirubin↗

PubMed1992

Tumor-cell dissociation at the invasion front: a new prognostic parameter in gastric cancer patients.

Tumor-cell dissociation (TCD) is a well-known feature at the invasion front of malignant tumors, but little attention has so far been paid to its biological significance. Therefore, the aim of the present study was to score the degree of TCD at the invasion front (TCD 0-3) in a retrospective series of 445 gastric cancer patients and to compare its prognostic significance with the parameters T-stage, tumor size, grade of tumor differentiation, lymph-node involvement and vascular invasion. We could show that highly significant differences (p less than 0.0001, log-rank test) existed between the 5-year survival rates of patients with different degrees of TCD (TCD 0: 92.3%; TCD 1: 62.1%; TCD 2: 41.2%. TCD 3:38.5%) and that these differences were independent of T-stage 2, tumor size and grade of tumor differentiation. Univariate Cox regression analysis showed that in intestinal-type carcinomas, T-stage (Chi-square: 45.2) followed by blood vessel and lymphatic vessel invasion (Chi-square: 43.6 and 40.0) had the highest prognostic value, whereas TCD (Chi-square: 31.5) revealed a prognostic value quite similar to that of lymph-node involvement (Chi-square: 35.1). This prognostic relevance was still present in multivariate Cox regression analysis, showing that the determination of TCD provided an increase in prognostic information which significantly (P = 0.026) exceeded the information obtained by the combination of T-stage and lymph-node involvement. Our data suggest that TCD is a new prognostic parameter, especially in those gastric carcinomas in which lymph-node involvement or vascular invasion are not present.

Adult↗