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Proteomics analysis to reveal biological pathways and predictive proteins in the survival of high-grade serous ovarian cancer.

ABSTRACT: High-grade serous ovarian cancer (HGSC) is an aggressive cancer with a worse clinical outcome. Therefore, studies about the prognosis of HGSC may provide therapeutic avenues to improve patient outcomes. Since genome alteration are manifested at the protein level, we integrated protein and mRNA data of ovarian cancer from The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) and utilized the sparse overlapping group lasso (SOGL) method, a new mechanism-driven variable selection method, to select dysregulated pathways and crucial proteins related to the survival of HGSC. We found that biosynthesis of amino acids was the main biological pathway with the best predictive performance (AUC?=?0.900). A panel of three proteins, namely EIF2B1, PRPS1L1 and MAPK13 were selected as potential predictive proteins and the risk score consisting of these three proteins has predictive performance for overall survival (OS) and progression free survival (PFS), with AUC of 0.976 and 0.932, respectively. Our study provides additional information for further mechanism and therapeutic avenues to improve patient outcomes in clinical practice.

SUBMITTER: Xie H

PROVIDER: S-EPMC5575023 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Proteomics analysis to reveal biological pathways and predictive proteins in the survival of high-grade serous ovarian cancer.

Xie Hongyu H Wang Wenjie W Sun Fengyu F Deng Kui K Lu Xin X Liu Huijuan H Zhao Weiwei W Zhang Yuanyuan Y Zhou Xiaohua X Li Kang K Hou Yan Y

Scientific reports 20170829 1

High-grade serous ovarian cancer (HGSC) is an aggressive cancer with a worse clinical outcome. Therefore, studies about the prognosis of HGSC may provide therapeutic avenues to improve patient outcomes. Since genome alteration are manifested at the protein level, we integrated protein and mRNA data of ovarian cancer from The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) and utilized the sparse overlapping group lasso (SOGL) method, a new mechanism-driven var ...[more]

PMID: 28852147

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Project description:ObjectiveStudies on low-grade serous ovarian cancer (LGSC) are limited by a low number of cases. The aim of this study was to define the prognostic significance of age, stage, and CA-125 levels on survival in a multi-institutional cohort of women with pathologically confirmed LGSC.MethodsWomen with LGSC were identified from the collaborative Ovarian Cancer Association Consortium (OCAC). Cases of newly diagnosed primary LGSC were included if peri-operative CA-125 levels were available. Age at diagnosis, FIGO stage, pre- and post-treatment CA-125 levels, residual disease, adjuvant chemotherapy, disease recurrence, and vital status were collected by the participating institutions. Progression-free (PFS) and overall survival (OS) were calculated. Multivariable (MVA) Cox proportional hazard models were used and hazard ratios (HR) calculated.ResultsA total of 176 women with LGSC were included in this study; 82% had stage III/IV disease. The median PFS was 2.3 years and the median OS was 6.4 years. Age at diagnosis was not significantly associated with worse PFS (p = 0.23) or OS (p = 0.3) (HR per year: 0.99; 95%CI, 0.96-1.01 and 0.98; 95%CI 0.95-1.01). FIGO stage III/IV was independently associated with PFS (HR 4.26, 95%CI 1.43-12.73) and OS (HR 1.69, 95%CI 0.56-5.05). Elevated CA-125 (≥35 U/mL) at diagnosis was not significantly associated with worse PFS (p = 0.87) or OS (p = 0.78) in MVA. Elevated CA-125 (≥35 U/mL) after completion of primary treatment was independently associated with worse PFS (HR 2.81, 95%CI 1.36-5.81) and OS (HR 6.62, 95%CI 2.45-17.92). In the MVA, residual disease was independently associated with PFS (0.022), but not OS (0.85).ConclusionAdvanced LGSC was associated with poor long-term prognosis. FIGO stage and abnormal post-treatment CA-125 level are key prognostic factors inversely associated with PFS and OS.Highlights1. Through a multi-center collaborative effort, data from 176 women with low-grade serous ovarian cancer were analyzed. 2. Although low-grade serous ovarian cancer is often considered indolent, the progression-free and overall survival are poor. 3. Elevated post-treatment CA-125 levels are independently associated with poor survival.

Project description:BackgroundETS transcription factors are known to act as either positive or negative regulators of the expression of genes involved in various biological processes. It was reported that ETS variant transcription factor 5 (ETV5), a key member of the ETS family, mainly plays a role as an potential oncogene in various malignant tumors. However, the role and mechanism of ETV5 in high-grade serous ovarian cancer (HGSOC) have not been elucidated.MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) assay was used to detect ETV5 messenger ribonucleic acid (mRNA) expression in 87 HGSOC tissues and 35 normal fallopian tube tissues. Western blotting and qRT-PCR were used to detect the protein and mRNA expression of ETV5 in six ovarian cancer (OC) and human embryonic cell lines. Knockdown or overexpression of ETV5 in HGSOC cell lines, Cell Counting Kit-8, colony formation, and transwell assays were used to detect HGSOC cell proliferation, invasion, and migration capabilities. The chi-square test was used to analyze the clinicopathological characteristics of HGSOC patients. Survival analysis was performed using the Kaplan-Meier method, and the log-rank test was used to analyze the correlation between ETV5 expression and HGSOC patient prognosis. Univariate and multivariate analyses using the Cox regression model were conducted to determine the independent significance of relevant clinical covariates.ResultsBioinformatic analysis demonstrated that ETV5 expression was significantly upregulated in OC (p < 0.05). qRT-PCR showed that ETV5 was significantly overexpressed in HGSOC tissues than in fallopian tube tissues (p < 0.05). qRT-PCR and western blotting assays demonstrated that ETV5 was relatively highly expressed in OC cell lines. ETV5 overexpression was positively associated with poor survival in HGSOC patients, therefore making it a high-risk factor for HGSOC progression. Furthermore, ETV5 promoted the proliferation, migration, and invasion capabilities of HGSOC cells.ConclusionETV5 has a carcinogenic effect in HGSOC and can be used as a clinically effective biomarker to determine the prognosis of HGSOC patients.

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Proteomics analysis to reveal biological pathways and predictive proteins in the survival of high-grade serous ovarian cancer.

Publications

Proteomics analysis to reveal biological pathways and predictive proteins in the survival of high-grade serous ovarian cancer.

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