Pancancer survival analysis of cancer hallmark genes

Abstract

Cancer hallmark genes are responsible for the most essential phenotypic characteristics of malignant transformation and progression. In this study, our aim was to estimate the prognostic effect of the established cancer hallmark genes in multiple distinct cancer types.RNA-seq HTSeq counts and survival data from 26 different tumor types were acquired from the TCGA repository. DESeq was used for normalization. Correlations between gene expression and survival were computed using the Cox proportional hazards regression and by plotting Kaplan-Meier survival plots. The false discovery rate was calculated to correct for multiple hypothesis testing.Signatures based on genes involved in genome instability and invasion reached significance in most individual cancer types. Thyroid and glioblastoma were independent of hallmark genes (61 and 54 genes significant, respectively), while renal clear cell cancer and low grade gliomas harbored the most prognostic changes (403 and 419 genes significant, respectively). The eight genes with the highest significance included BRCA1 (genome instability, HR=4.26, p<1E-16), RUNX1 (sustaining proliferative signaling, HR=2.96, p=3.1E-10) and SERPINE1 (inducing angiogenesis, HR=3.36, p=1.5E-12) in low grade glioma, CDK1 (cell death resistance, HR=5.67, p=2.1E-10) in kidney papillary carcinoma, E2F1 (tumor suppressor, HR=0.38, p=2.4E-05) and EREG (enabling replicative immortality, HR=3.23, p=2.1E-07) in cervical cancer, FBP1 (deregulation of cellular energetics, HR=0.45, p=2.8E-07) in kidney renal clear cell carcinoma and MYC (invasion and metastasis, HR=1.81, p=5.8E-05) in bladder cancer.We observed unexpected heterogeneity and tissue specificity when correlating cancer hallmark genes and survival. These results will help to prioritize future targeted therapy development in different types of solid tumors.

Targeting lactate dehydrogenase a improves radiotherapy efficacy in non-small cell lung cancer: from bedside to bench

“…Levels of LDHA mRNA expression in NSCLC tumor and normal tissue were compared by GEPIA browser ( http://gepia.cancer-pku.cn/ ), a newly developed interactive web server for analyzing the RNA sequencing expression data of 9736 tumors and 8587 normal samples from the TCGA and the GTEx projects, which provides customizable functions such as tumor/normal differential expression analysis, profiling according to cancer types or pathological stages, patient survival analysis, similar gene detection, correlation analysis and dimensionality reduction analysis [ 17 ]. The association among LDHA mRNA expression level and survival of NSCLC patients was investigated by data mining in the Kaplan–Meier plotter database ( http://kmplot.com ), an online database integrating gene expression and survival information simultaneously download from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) [ 18 ]. The detailed GEO information included are as follows: CaArray, GSE14814, GSE19188, GSE29013, GSE30219, GSE31210, GSE3141, GSE31908, GSE37745, GSE4573, and GSE50081 [ 19 ].…”

Epigenetic Mechanisms Are Involved in the Oncogenic Properties of ZNF518B in Colorectal Cancer

“…The equality of the variances was analysed by the Levene test. To construct the Kaplan–Meier curves for disease-free survival using the data from the TCGA database, the procedure described elsewhere [ 59 , 60 ] was followed. When our experimentally determined isoform ratio was used, data were categorised into high and low groups according to the median values.…”

Comprehensive Analysis of the Prognostic Value of ITGB Superfamily Members in Gastric Cancer Using Bioinformatics Analysis

“…The pathological stage analysis and survival analysis of ITGBs in STAD, Student's t test was used to generate a p value and the survival analysis was performed using a Kaplan-Meier curve. Kaplan-Meier Plotter (http://kmplot.com/analysis/) allows users to evaluate the effect of mRNA, miRNA or protein on the survival in breast, ovarian, lung and gastric cancer [17]. The prognostic value of ITGBs in patients with STAD was explored and exhibited together with the HR index, 95% CI, p value and number at risk in the gures.…”