Revealing Prognosis-Related Pathways at the Individual Level by a Comprehensive Analysis of Different Cancer Transcription Data

Abstract

Identifying perturbed pathways at an individual level is important to discover the causes of cancer and develop individualized custom therapeutic strategies. Though prognostic gene lists have had success in prognosis prediction, using single genes that are related to the relevant system or specific network cannot fully reveal the process of tumorigenesis. We hypothesize that in individual samples, the disruption of transcription homeostasis can influence the occurrence, development, and metastasis of tumors and has implications for patient survival outcomes. Here, we introduced the individual-level pathway score, which can measure the correlation perturbation of the pathways in a single sample well. We applied this method to the expression data of 16 different cancer types from The Cancer Genome Atlas (TCGA) database. Our results indicate that different cancer types as well as their tumor-adjacent tissues can be clearly distinguished by the individual-level pathway score. Additionally, we found that there was strong heterogeneity among different cancer types and the percentage of perturbed pathways as well as the perturbation proportions of tumor samples in each pathway were significantly different. Finally, the prognosis-related pathways of different cancer types were obtained by survival analysis. We demonstrated that the individual-level pathway score (iPS) is capable of classifying cancer types and identifying some key prognosis-related pathways.