Prognostic nomogram of hypoxia-related genes predicting overall survival of colorectal cancer-Analysis of TCGA database

Abstract

Hypoxia-related gene (HRG) expression is associated with survival outcomes of colorectal cancer (CRC). Our aim was developing a nomogram predicting CRC overall survival (OS) with HRGs and clinicopathological factors. The Cancer Genome Atlas (TCGA) database was used as discovery cohort and two Gene Expression Omnibus databases (GSE39582 and GSE41258) served as validation cohorts. A genetic risk score model prognosticating OS was developed using mRNA expression level of HRGs. Nomogram predicting OS was developed using genetic risk score model and clinicopathological variables. The genetic risk score model included four HRGs (HSPA1L, PUM1, UBE2D2, and HSP27) and successfully prognosticated OS of discovery and two validation cohorts (p < 0.001 for TCGA discovery set, p < 0.003 for the GSE39582 and p = 0.042 for the GSE41258 datasets). Nomogram included genetic risk score, age, and TNM stage. Harrell's concordance indexes of the nomogram were higher than those of TNM stage alone in the discovery set (0.77 vs. 0.69, p < 0.001), GSE39582 (0.65 vs. 0.63, p < 0.001), and GSE41258 datasets (0.78 vs. 0.77, p < 0.001). Our nomogram successfully predicted OS of CRC patients. The mRNA expression level of the HRGs might be useful as an ancillary marker for prognosticating CRC outcome.

Figure 1

Gene selection flow chart.

Figure 2

Twenty-nine hypoxia-related genes which were significantly associated with OS by log-rank test. Among them, 16 genes were associated with overall survival in univariate analysis and are highlighted in bold.

Figure 3

Genetic risk score model developed with 4 hypoxia-related genes.

Figure 4

Kaplan-Meier plot of the genetic risk score (high risk vs. low risk, threshold: median score) for (a) TCGA discovery set, (b) GSE39582 validation set, and (c) GSE41258 validation set.

Figure 5

Nomogram predicting 3- and 5-year overall survival of colorectal cancer patients.

Figure 6

Calibration curve for nomogram-predicting (a) 3-year and (b) 5-year overall survival. The X-axis is nomogram-predicted survival probability and the Y-axis is observed survival probability respectively. Red, green and blue solid lines represent the performance of the nomogram relative to the 45-degree line, indicating perfect prediction. Receiver operating characteristic curves assessing the discriminating ability of the nomogram in predicting (c) 3-year and (d) 5-year overall survival.