Predicting STAT1 as a prognostic marker in patients with solid cancer

Background: Aberrant activities of signal transducer and activator of transcription 1 (STAT1) have been implicated in cancer development. However, the prognostic value of STAT1 remains unclear. This report identified the role of STAT1 in prognosis in patients with solid cancer through open literature and The Cancer Genome Atlas (TCGA) database. Methods: Published articles were obtained from PubMed, Web of Science, and Embase databases according to a search strategy up to October 2019. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted to assess the prognostic factors of patients. TCGA datasets were used to explore the prognostic value of STAT1 in various cancers. Results: A total of 15 studies incorporating 2839 patients with solid cancers were included. Pooled data showed that overexpressed STAT1 favored long overall survival (OS) (HR = 0.604, 95% CI = 0.431–0.846, p = 0.003) and disease-specific survival (DSS) (HR = 0.650, 95% CI = 0.512–0.825, p = 0.000). In subgroup analyses, highly expressed STAT1 was correlated with long OS of patients with high-grade serous ovarian cancer and oral squamous cell carcinoma. Data extracted from TCGA datasets unveiled that STAT1 expression was significantly higher in 12 cancers (e.g. bladder and breast) than their adjacent normal tissues. Again, highly expressed STAT1 favored long OS of patients with ovarian cancer as well as rectum adenocarcinoma, sarcoma, and skin cutaneous melanoma. However, in renal carcinoma, brain lower grade glioma, lung adenocarcinoma, and pancreatic cancer, highly expressed STAT1 was correlated with poor OS of patients. Particularly in renal carcinoma, increased STAT1 expression was associated with high grade, later stage, large tumor size, and lymph node and distant metastasis. Conclusion: STAT1 has been identified to have prognostic value in patients with solid cancer. Highly expressed STAT1 may predict prognosis in cancer patients based on their tumor types.

Download Full-text

The Clinical Significance and Prognostic Value of HER2 Expression in Bladder Cancer: a Systematic Review and Meta-analysis

10.21203/rs.3.rs-135089/v1 ◽

2020 ◽

Author(s):

Kai Gan ◽

Yue Gao ◽

KuangZheng Liu ◽

Bin Xu ◽

Ming Chen

Keyword(s):

Bladder Cancer ◽

Clinical Significance ◽

Prognostic Value ◽

Meta Analysis ◽

Growth Factor Receptor ◽

Tumor Stage ◽

The Cancer Genome Atlas ◽

Her2 Expression ◽

Large Tumor ◽

Normal Tissues

Abstract Objective: Human Epidermal Growth Factor Receptor 2 (HER2) is highly expressed in a variety of tumors and associated with patients’ prognosis, but its role in bladder cancer remains unclear. We conducted this meta-analysis to explore the clinical significance and prognostic value of HER2 in bladder cancer and its potentiality as an immunotherapy target.Methods: PubMed was searched for studies published between January 1, 2000 and January 1, 2020. The odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95%CIs) were used to investigate the relationship between HER2 and bladder cancer. UALCAN website was used to obtain TCGA (The cancer genome atlas) database.Results: Our study includes 14 articles, 1398 patients. HER2 expression was significantly higher in bladder cancer than in normal tissues. Our meta-analysis results did not reveal any effect of gender on the expression of HER2 levels in bladder cancer patients. However, HER2 expression in male patients was significantly higher than that in women according to TCGA databases. HER2 expression was also associated with carcinoma in situ, multifocal tumors, large tumor size, high tumor stage and grade, lymph node metastases, risk of recurrence and progression, low recurrence-free survival (RFS) rate. HER2 expression status had no effect on overall survival.Conclusions: Our meta-analysis showed that HER2 expression was related to pathological malignancy and poor prognosis in bladder cancer which indicated that it could be used as an effective biomarker and therapeutic target.

Download Full-text

Prognostic and immunological role of Fam20C in pan-cancer

Bioscience Reports ◽

10.1042/bsr20201920 ◽

2021 ◽

Vol 41 (1) ◽

Author(s):

Xinpeng Liu ◽

Yuanbo Zhan ◽

Wenxia Xu ◽

Xiaoyao Liu ◽

Yawei Geng ◽

...

Keyword(s):

Prognostic Value ◽

Sequence Similarity ◽

Expression Patterns ◽

The Cancer Genome Atlas ◽

Lower Grade ◽

Tumor Cell Migration ◽

Immune Infiltration ◽

Normal Tissues ◽

Kaplan Meier ◽

Pan Cancer

Abstract Background: The family with sequence similarity 20-member C (Fam20C) kinase plays important roles in physiopathological process and is responsible for majority of the secreted phosphoproteome, including substrates associated with tumor cell migration. However, it remains unclear whether Fam20C plays a role in cancers. Here, we aimed to analyze the expression and prognostic value of Fam20C in pan-cancer and to gain insights into the association between Fam20C and immune infiltration. Methods: We analyzed Fam20C expression patterns and the associations between Fam20C expression levels and prognosis in pan-cancer via the ONCOMINE, TIMER (Tumor Immune Estimation Resource), PrognoScan, GEPIA (Gene Expression Profiling Interactive Analysis), and Kaplan–Meier Plotter databases. After that, GEPIA and TIMER databases were applied to investigate the relations between Fam20C expression and immune infiltration across different cancer types, especially BLCA (bladder urothelial carcinoma), LGG (brain lower grade glioma), and STAD (stomach adenocarcinoma). Results: Compared with adjacent normal tissues, Fam20C was widely expressed across many cancers. In general, Fam20C showed a detrimental role in pan-cancer, it was positively associated with poor survival of BLCA, LGG, and STAD patients. Specifically, based on TCGA (The Cancer Genome Atlas) database, a high expression level of Fam20C was associated with worse prognostic value in stages T2–T4 and stages N0–N2 in the cohort of STAD patients. Moreover, Fam20C expression had positive associations with immune infiltration, including CD4+ T cells, macrophages, neutrophils, and dendritic cells, and other diverse immune cells in BLCA, LGG, and STAD. Conclusion: Fam20C may serve as a promising prognostic biomarker in pan-cancer and has positive associations with immune infiltrates.

Download Full-text

Prognostic value of CLIC3 mRNA overexpression in bladder cancer

PeerJ ◽

10.7717/peerj.8348 ◽

2020 ◽

Vol 8 ◽

pp. e8348

Author(s):

Mei Chen ◽

Shufang Zhang ◽

Xiaohong Wen ◽

Hui Cao ◽

Yuanhui Gao

Keyword(s):

Gene Expression ◽

Bladder Cancer ◽

Mrna Expression ◽

Prognostic Value ◽

Multivariate Analyses ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Functional Enrichment ◽

Receptor Interaction ◽

Normal Tissues

Background Human intracellular chloride channel 3 (CLIC3) is involved in the development of various cancers, but the expression and prognostic value of CLIC3 mRNA in bladder cancer (BC) remain unclear. Methods The gene expression data and clinical information of CLIC3 were obtained from the Gene Expression Omnibus (GEO) database and verified in the Oncomine and The Cancer Genome Atlas (TCGA) database. The expression of CLIC3 mRNA in BC tissues and adjacent normal tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The Kaplan-Meier method was used to analyze the relationship between the expression of CLIC3 mRNA and the prognosis of BC. Cox univariate and multivariate analyses were performed on the overall survival and tumor-specific survival of BC patients. The genes coexpressed with CLIC3 were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). CLIC3-related signal transduction pathways in BC were explored with gene set enrichment analysis (GSEA). Results The expression of CLIC3 mRNA in BC tissues was higher than that in normal tissues (P < 0.01). High CLIC3 mRNA expression was associated with age (P = 0.021) and grade (P = 0.045) in BC patients. High CLIC3 mRNA expression predicted a poor prognosis in BC patients (P < 0.05). Cox univariate and multivariate analyses showed that high CLIC3 mRNA expression was associated with tumor-specific survival in BC patients (P < 0.05). Functional enrichment analyses indicated that CLIC3 may be significantly associated with the cell cycle, focal adhesion, the extracellular matrix (ECM) receptor interaction and the P53 signaling pathway. Conclusions CLIC3 mRNA is highly expressed in BC, and its high expression is related to the adverse clinicopathological factors and prognosis of BC patients. CLIC3 can be used as a biomarker for the prognosis of BC patients.

Download Full-text

TCR Clonality and Genomic Instability Signatures as Prognostic Biomarkers in High Grade Serous Ovarian Cancer

Cancers ◽

10.3390/cancers13174394 ◽

2021 ◽

Vol 13 (17) ◽

pp. 4394

Author(s):

Julie Lecuelle ◽

Romain Boidot ◽

Hugo Mananet ◽

Valentin Derangère ◽

Juliette Albuisson ◽

...

Keyword(s):

T Cell ◽

Genomic Instability ◽

Survival Data ◽

Prognostic Value ◽

Prognostic Biomarker ◽

Copy Number Variant ◽

Cell Receptor ◽

The Cancer Genome Atlas ◽

High Grade ◽

Cell Infiltrate

Purpose: Immune infiltration is a prognostic factor in high-grade serous ovarian carcinoma (HGSC) but immunotherapy efficacy is disappointing. Genomic instability is now used to guide the therapeutic value of PARP inhibitors. We aimed to investigate exome-derived parameters to assess the tumor microenvironment according to genomic instability profile. Methods: We used the HGSC TCGA (the cancer genome atlas) dataset with genomic characteristics, including homologous recombination deficiency (HRD), copy number variant (CNV) signatures, TCR (T cell receptor) clonality and abundance of tissue-infiltrating immune and stromal cell populations. We then investigated the relationship with survival data. Results: In 578 HGSC patients, HRD status, CNV signature 7 and TCR clonality were associated with longer survival. The combination of high CNV signature 7 expression and HRD status or high CNV signature 3 expression and high TCR clonality was associated with a trend towards longer survival compared to each variable alone. Combining T cell infiltrate and TCR clonality improved the prognostic value compared to T cells infiltration alone. Prognostic value of TCR clonality was confirmed in an independent cohort. Conclusions: TCR clonality is an emerging prognostic biomarker that improves T cell infiltrate information. Analysis of TCR clonality combined with genomic instability could be an interesting prognostic biomarker.

Download Full-text

NaPi- II b as a potential diagnostic and prognostic biomarker in ovarian cancers

10.1101/394759 ◽

2018 ◽

Author(s):

Shoufeng Zhao ◽

Zhipeng Wang

Keyword(s):

Ovarian Cancer ◽

Cancer Cell Line ◽

Normal Tissues ◽

Diagnosis And Prognosis ◽

Kaplan Meier ◽

Potential Biomarker ◽

Tumor Types ◽

First Time ◽

Kaplan Meier Plotter ◽

Normal Controls

ABSTRACTOvarian cancer (OC) is commonly diagnosed at an advanced stage due to a lack of effective biomarkers and specificity required for accurate clinical diagnosis. The purpose of this study was to estimate the diagnosis and prognosis of the NaPi- II b in ovarian cancer. Herein, by performing data mining using the databases of Oncomine and Cancer Cell Line Encyclopedia (CCLE), we are for the first time to report that the expression level of NaPi- II b transcripts in a variety of tumor types compared with the normal controls. Based on Kaplan-Meier plotter, we investigated the prognostic values of NaPi- II b specifically high expressed in OC patients. The results of the Oncomine analysis showed that relative expression of NaPi- II b was distinctly high in OC tissues vs. normal tissues. CCLE analysis indicated that the expression of NaPi- II b in OC cell lines expressed the highest level in all cancer lines. In overall survival (OR) analysis, NaPi- II b mRNA high expressions were correlated to worse OR in OC patients. These results indicate that NaPi- II b may be a novel potential biomarker for determining the diagnosis and predicting the prognosis of OC.

Download Full-text

The Prognostic Value of PARP Expression in High-Grade Epithelial Ovarian Cancer

Pathology & Oncology Research ◽

10.1007/s12253-020-00856-6 ◽

2020 ◽

Vol 26 (4) ◽

pp. 2549-2555

Author(s):

Szabolcs Molnár ◽

Lívia Beke ◽

Gábor Méhes ◽

Róbert Póka

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Prognostic Value ◽

High Grade

Download Full-text

Combined Immunoscore of CD103 and CD3 Identifies Long-Term Survivors in High-Grade Serous Ovarian Cancer

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000672 ◽

2016 ◽

Vol 26 (4) ◽

pp. 671-679 ◽

Cited By ~ 28

Author(s):

Hans-Christian Bösmüller ◽

Philipp Wagner ◽

Janet Kerstin Peper ◽

Heiko Schuster ◽

Deborah Lam Pham ◽

...

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Clinical Outcome ◽

Prognostic Value ◽

Intraepithelial Lymphocytes ◽

High Grade ◽

Serous Ovarian Cancer ◽

Term Survival ◽

Cell Counts

ObjectiveIncreased numbers of tumor-infiltrating lymphocytes (TILs) in high-grade serous ovarian cancer (HGSC) are associated with improved clinical outcome. Intraepithelial localization of TILs might be regulated by specific homing receptors, such as CD103, which is widely expressed by intraepithelial lymphocytes. Given the emerging role of CD103+ TILs, we aimed to assess their contribution to the prognostic value of immunoscoring in HGSC.MethodsThe density of intratumoral CD3+ and CD103+ lymphocytes was examined by immunohistochemistry on a tissue microarray of a series of 135 patients with advanced HGSC and correlated with CD4+, CD8+, CD56+, FoxP3+, and TCRγ+ T-cell counts, as well as E-cadherin staining and conventional prognostic parameters and clinical outcome.ResultsBoth the presence of CD103+ cells, as well as high numbers of intraepithelial CD3+ lymphocytes (CD3E), showed a significant correlation with overall survival, in the complete series, as well as in patients with optimal debulking and/or platinum sensitivity. Combining CD3 and CD103 counts improved prognostication and identified 3 major subgroups with respect to overall survival. The most pronounced effect was demonstrated for patients with optimally resected and platinum-sensitive tumors. Patients with CD3high/CD103high tumors showed a 5-year survival rate at 90%, CD3low/CD103high at 63%, and CD3low/CD103low at 0% (P < 0.001).ConclusionsThese results suggest that combined assessment of CD103 and CD3 counts improves the prognostic value of TIL counts in HGSC and might identify patients with early relapse or long-term survival based on the type and extent of the immune response.

Download Full-text

Abstract 442: RASSF1A gene promoter methylation in primary tumors, adjacent morphologically normal tissues and plasma samples of patients with high grade serous ovarian cancer

10.1158/1538-7445.am2016-442 ◽

2016 ◽

Author(s):

Lydia Giannopoulou ◽

Issam Chebouti ◽

Kitty Pavlakis ◽

Sabine Kasimir-Bauer ◽

Evi S. Lianidou

Keyword(s):

Ovarian Cancer ◽

Promoter Methylation ◽

Gene Promoter ◽

High Grade ◽

Plasma Samples ◽

Serous Ovarian Cancer ◽

Primary Tumors ◽

Rassf1a Gene ◽

Normal Tissues

Download Full-text

The Gasdermin E gene Potential as a Pan-Cancer Biomarker, While Discriminating between Different Tumor Types

Cancers ◽

10.3390/cancers11111810 ◽

2019 ◽

Vol 11 (11) ◽

pp. 1810 ◽

Cited By ~ 3

Author(s):

Joe Ibrahim ◽

Ken Op de Beeck ◽

Erik Fransen ◽

Marc Peeters ◽

Guy Van Camp

Keyword(s):

The Cancer Genome Atlas ◽

Tumor Type ◽

E Gene ◽

Normal Tissues ◽

Incidence And Mortality ◽

Cancer Genome Atlas ◽

Cancer Setting ◽

Tumor Types ◽

Methylation Patterns ◽

Pan Cancer

Due to the elevated rates of incidence and mortality of cancer, early and accurate detection is crucial for achieving optimal treatment. Molecular biomarkers remain important screening and detection tools, especially in light of novel blood-based assays. DNA methylation in cancer has been linked to tumorigenesis, but its value as a biomarker has not been fully explored. In this study, we have investigated the methylation patterns of the Gasdermin E gene across 14 different tumor types using The Cancer Genome Atlas (TCGA) methylation data (N = 6502). We were able to identify six CpG sites that could effectively distinguish tumors from normal samples in a pan-cancer setting (AUC = 0.86). This combination of pan-cancer biomarkers was validated in six independent datasets (AUC = 0.84–0.97). Moreover, we tested 74,613 different combinations of six CpG probes, where we identified tumor-specific signatures that could differentiate one tumor type versus all the others (AUC = 0.79–0.98). In all, methylation patterns exhibited great variation between cancer and normal tissues, but were also tumor specific. Our analyses highlight that a Gasdermin E methylation biomarker assay, not only has the potential for being a methylation-specific pan-cancer detection marker, but it also possesses the capacity to discriminate between different types of tumors.

Download Full-text