Dataset Information

A five-gene based risk score with high prognostic value in colorectal cancer.

ABSTRACT: Colorectal cancer (CRC) is one of the most frequently occurring malignancies worldwide. The outcomes of patients with similar clinical symptoms or at similar pathological stages remain unpredictable. This inherent clinical diversity is most likely due to the genetic heterogeneity. The present study aimed to create a predicting tool to evaluate patient survival based on genetic profile. Firstly, three Gene Expression Omnibus (GEO) datasets (GSE9348, GSE44076 and GSE44861) were utilized to identify and validate differentially expressed genes (DEGs) in CRC. The GSE14333 dataset containing survival information was then introduced in order to screen and verify prognosis-associated genes. Of the 66 DEGs, the present study screened out 46 biomarkers closely associated to patient overall survival. By Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, it was demonstrated that these genes participated in multiple biological processes which were highly associated with cancer proliferation, drug-resistance and metastasis, thus further affecting patient survival. The five most important genes, MET proto-oncogene, receptor tyrosine kinase, carboxypeptidase M, serine hydroxymethyltransferase 2, guanylate cyclase activator 2B and sodium voltage-gated channel a subunit 9 were selected by a random survival forests algorithm, and were further made up to a linear risk score formula by multivariable cox regression. Finally, the present study tested and verified this risk score within three independent GEO datasets (GSE14333, GSE17536 and GSE29621), and observed that patients with a high risk score had a lower overall survival (P<0.05). Furthermore, this risk score was the most significant compared with other predicting factors including age and American Joint Committee on Cancer stage, in the model, and was able to predict patient survival independently and directly. The findings suggest that this survival associated DEGs-based risk score is a powerful and accurate prognostic tool and is promisingly implemented in a clinical setting.

SUBMITTER: Pan Y

PROVIDER: S-EPMC5754913 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A five-gene based risk score with high prognostic value in colorectal cancer.

Pan Yida Y Zhang Hongyang H Zhang Mingming M Zhu Jie J Yu Jianghong J Wang Bangting B Qiu Jigang J Zhang Jun J

Oncology letters 20170928 6

Colorectal cancer (CRC) is one of the most frequently occurring malignancies worldwide. The outcomes of patients with similar clinical symptoms or at similar pathological stages remain unpredictable. This inherent clinical diversity is most likely due to the genetic heterogeneity. The present study aimed to create a predicting tool to evaluate patient survival based on genetic profile. Firstly, three Gene Expression Omnibus (GEO) datasets (GSE9348, GSE44076 and GSE44861) were utilized to identif ...[more]

PMID: 29344121

Similar Datasets

Project description:BackgroundGastric adenocarcinoma is an important contributor to cancer mortality and morbidity. This study aimed to explore the prognostic value of mutation patterns in gastric adenocarcinoma.Materials and methodsWe extracted somatic mutation data for 437 gastric adenocarcinoma samples from The Cancer Genome Atlas (TCGA) Stomach Adenocarcinoma (STAD) cohort. Kaplan-Meier survival in the R package maftools was used to analyze associations between mutations and survival. Multivariate Cox proportional model was used to establish risk formula. A four-gene-based risk score was developed to predict the overall survival of patients with gastric adenocarcinoma. We used the Tianjin cohort dataset with survival information to further evaluate the clinical value of this mutation signature.ResultsForty-five survival-related mutated genes were identified and verified, most of which were co-occurring in their mutation pattern and co-occurring with MLH3 and polymerase ϵ (POLE) mutations. Gastric adenocarcinoma samples with the 45 mutated genes had a significantly higher mutation count. Four-gene [UTRN, MUC16, coiled-coil domain-containing protein 178 (CCDC178), and HYDIN] mutation status was used to build a prognostic risk score that could be translated into the clinical setting. The association between the four-gene-based signature and overall survival remained statistically significant after controlling for age, sex, TNM stage, and POLE mutation status in the multivariate model [hazard ratio (HR), 1.88; 95% CI, 1.33-2.7; p < 0.001]. The prognostic significance of the four-gene-based risk score identified in TCGA cohort was validated in the Tianjin cohort.ConclusionA four-mutated gene risk formula was developed that correlated with the overall survival of patients with gastric adenocarcinoma using a multivariable Cox regression model. In two independent genomic datasets from TCGA and Tianjin cohorts, low risk scores were associated with higher tumor mutation loads and improved outcome in patients with gastric adenocarcinoma. This finding may have implications for prognostic prediction and therapeutic guidance for gastric adenocarcinoma.

Project description:BackgroundTargeted therapeutic strategies for advanced colorectal cancer (CRC) have been limited. STING is crucial to the antitumor immunotherapy, for it stimulates IFN signaling to mediate the crosstalk between innate and adaptive immune responses. Emerging evidence suggests that STING also contributes to the prognosis of CRC. However, prognostic models relating to STING have not yet been explored.MethodsA total of 431 CRC samples from the TCGA database were analyzed to explore the prognostic value of STING-related genes. We trained prognostic models using the multivariate Cox regression. A STING-related prognostic score (SPS) was calculated as the gene expression multiplied by the corresponding coefficients of the final model. A backward stepAIC strategy was adopted to select the optimal model. A nomogram was used to personalize medical decisions for CRC.ResultsThe expression level of STING was upregulated in the CMS1 subtype (P=0.036). Among STING-related genes, DHX9 (HR =0.72, P=0.01), IRF2 (HR =1.34, P=0.022), and POLR1D (HR =1.23, P=0.038) showed significant prognostic value. The SPS was proven to be an independent risk factor (training: HR =2.9, P=0.00013; validation: HR =3.02, P=0.01), and outperformed random classifiers in identifying high-risk CRC. The high SPS group was characterized by less genomic aberrations, upregulated IL6-JAK-STAT3 and IL2-STAT5 signaling pathways, increased expression of TIM-3, increased infiltration of regulatory T (Treg) cells and T helper 17 (Th17) cells, and decreased infiltration of M0 macrophages. Finally, the nomogram based on the SPS and clinical factors showed good performance in CRC.ConclusionsSPS is an independent risk factor that could identify high-risk CRC. While ICBs may benefit patients of the CMS1 subtype, for the CMS2, CMS3, and CMS4 subtypes in the high SPS group, STING agonists and immunotherapies targeting the Th17 axis may be beneficial. Finally, the SPS-based nomogram could help advance personalized medical decisions for CRC.

Dataset Information

A five-gene based risk score with high prognostic value in colorectal cancer.

Publications

A five-gene based risk score with high prognostic value in colorectal cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets