Construction and Validation of an Immune-Related Prognostic Model Based on TP53 Status in Colorectal Cancer.

Xiaojuan Zhao,Jianzhong Liu,Shuzhen Liu,Fangfang Yang,Erfei Chen

doi:10.3390/cancers11111722

Abstract

Growing evidence has indicated that prognostic biomarkers have a pivotal role in tumor and immunity biological processes. TP53 mutation can cause a range of changes in immune response, progression, and prognosis of colorectal cancer (CRC). Thus, we aim to build an immunoscore prognostic model that may enhance the prognosis of CRC from an immunological perspective. We estimated the proportion of immune cells in the GSE39582 public dataset using the CIBERSORT (Cell type identification by estimating relative subset of known RNA transcripts) algorithm. Prognostic genes that were used to establish the immunoscore model were generated by the LASSO (Least absolute shrinkage and selection operator) Cox regression model. We established and validated the immunoscore model in GEO (Gene Expression Omnibus) and TCGA (The Cancer Genome Atlas) cohorts, respectively; significant differences of overall survival analysis were found between the low and high immunoscore groups or TP53 subgroups. In the multivariable Cox analysis, we observed that the immunoscore was an independent prognostic factor both in the GEO cohort (HR (Hazard ratio) 1.76, 95% CI (confidence intervals): 1.26–2.46) and the TCGA cohort (HR 1.95, 95% CI: 1.20–3.18). Furthermore, we established a nomogram for clinical application, and the results suggest that the nomogram is a better predictive model for prognosis than immunoscore or TNM staging.

Highlights

TP53, one of the most common tumor suppressor genes, both in colorectal cancer (CRC) and other tumor types, has been well known to play an important role in tumor progression and malignant phenotype of CRC
We established a nomogram for clinical application, and the results suggest that the nomogram is a better predictive model for prognosis than immunoscore or TNM staging
The Kaplan-Meier analysis showed that there is no significant not enriched in any immune and cancer-related signaling pathways (Supplemental Table S2). These findings difference between TP53 mutation status and overall survival in patients with CRC in Gene Expression Omnibus (GEO) and indicate that cohorts, TP53 mutation only affects theprevious proliferation, apoptosis, and migration of CRC, and which not is consistent with research plays a crucial role in immune response

Summary

Introduction

TP53, one of the most common tumor suppressor genes, both in colorectal cancer (CRC) and other tumor types, has been well known to play an important role in tumor progression and malignant phenotype of CRC. Novel driver genes are constantly found in colorectal cancer [1], TP53 alteration is still a main characterization of genetic spectrum in human CRC. The effects of TP53 as a driver gene in the genomic and biological processes of tumor cells have been widely investigated. Growing evidence suggests that TP53 concurrently contributes to the regulation of tumor immune response [2,3,4,5,6]; a significant activation of inflammatory and innate immune pathways in CRC caused by TP53 mutation have already been found [7]. TP53 can promote immune response by directly activating key regulatory factors in immune signaling pathways [2]. Several TP53 target genes currently have found function in cytokine production and inflammation pathways [8,9,10,11]

Objectives

Methods

Results

Conclusion