Identifying Potential Biomarkers of Prognostic Value in Colorectal Cancer via Tumor Microenvironment Data Mining.

Lei Li,Guangyi Fan,Xiao Du

doi:10.3389/fgene.2021.787208

Abstract

Colorectal cancer (CRC) is a common cancer that has increased rapidly worldwide in the past decades with a relatively high mortality rate. An increasing body of evidence has highlighted the importance of infiltrating immune and stromal cells in CRC. In this study, based on gene expression data of CRC patients in TCGA database we evaluated immune and stromal scores in tumor microenvironment using ESTIMATE method. Results showed there was potential correlation between these scores and the prognosis, and that patients with higher immune score and lower stromal score had longer survival time. We found that immune score was correlated with clinical characteristics including tumor location, tumor stage, and survival time. Specifically, the right-sided colon cancer had markedly elevated immune score, compared to left-sided colon cancer and rectal cancer. These results might be useful for understanding tumor microenvironment in colorectal cancer. Through the differential analysis we got a list of genes significantly associated with immune and stromal scores. Gene Set Enrichment and protein-protein interaction network analysis were used to further illustrate these differentially expressed genes. Finally, 15 hub genes were identified, and three (CXCL9, CXCL10 and SELL) of them were validated with favorable outcomes in CRC patients. Our result suggested that these tumor microenvironment related genes might be potential biomarkers for the prognosis of CRC.

Highlights

Colorectal cancer (CRC) is one of the most commonly occurring cancers, whose incidence occupies 10% of all cancer diagnoses (Sung et al, 2021; Wong et al, 2021)
Patients were diagnosed with colorectal cancer between 1998 and 2013 and their sequencing and clinical information were collected into the The Cancer Genome Atlas (TCGA) database
What’s more, we found immune score was significantly associated with tumor location and the Rightsided colon cancer (RCC) had the highest immune score in GSE41258 dataset (Supplementary Figure S2B, p-value 0.032), which indicated that immune score might be predictive in the classification of CRC tumor location

Summary

Introduction

Colorectal cancer (CRC) is one of the most commonly occurring cancers, whose incidence occupies 10% of all cancer diagnoses (Sung et al, 2021; Wong et al, 2021). Rightsided colon cancer (RCC) differs from the left-sided colon cancer (LCC) and rectal cancer (RC) in pathogenesis and prognosis, exhibiting distinct molecular characteristics and histology (Baran et al, 2018; Imperial et al, 2018; Siegel et al, 2020). CRC screening is not common and the diagnosis is usually made after the onset of symptoms. Because the tumor status and TNM stage at diagnosis have a fundamental role in CRC prognosis, early symptom investigation and diagnosis are of high importance (Bosch et al, 2011; Kawakami et al, 2015).

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Conclusion