SERPINE1 associated with remodeling of the tumor microenvironment in colon cancer progression: a novel therapeutic target

Shaokun Wang,Zuolong Liu,Xiangwei Meng,Li Pang

doi:10.1186/s12885-021-08536-7

Shaokun Wang, Zuolong Liu + Show 2 more

Open Access

https://doi.org/10.1186/s12885-021-08536-7

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Journal: BMC Cancer	Publication Date: Jul 3, 2021
Citations: 37	License type: open-access

Affiliation: First Hospital of Jilin University, Jilin University

Abstract

BackgroundThe change of immune cell infiltration essentially influences the process of colorectal cancer development. The infiltration of immune cells can be regulated by a variety of genes. Thus, modeling the immune microenvironment of colorectal cancer by analyzing the genes involved can be more conducive to the in-depth understanding of carcinogenesis and the progression thereof.MethodsIn this study, the number of stromal and immune cells in malignant tumor tissues were first estimated by using expression data (ESTIMATE) and cell-type identification with relative subsets of known RNA transcripts (CIBERSORT) to calculate the proportion of infiltrating immune cell and stromal components of colon cancer samples from the Cancer Genome Atlas database. Then the relationship between the TMN Classification and prognosis of malignant tumors was evaluated.ResultsBy investigating differentially expressed genes using COX regression and protein-protein interaction network (PPI), the candidate hub gene serine protease inhibitor family E member 1 (SERPINE1) was found to be associated with immune cell infiltration. Gene Set Enrichment Analysis (GSEA) further projected the potential pathways with elevated SERPINE1 expression to carcinogenesis and immunity. CIBERSORT was subsequently utilized to investigate the relationship between the expression differences of SERPINE1 and immune cell infiltration and to identify eight immune cells associated with SERPINE1 expression.ConclusionWe found that SERPINE1 plays a role in the remodeling of the colon cancer microenvironment and the infiltration of immune cells.

Highlights

The change of immune cell infiltration essentially influences the process of colorectal cancer development
Malignant tumors are characterized as exhibiting unlimited multiplication, evasion from growth and evading immune destruction [1], all of which are pathogenically related to the tumor microenvironment (TME) [2]
To gain a more fundamental understanding of the molecular mechanism of TME remodeling in colon cancer progression, we propose here a computerized bioinformatics tool for identifying a candidate gene(s) from the Cancer Genome Atlas (TCGA) with regulatory functions in tumorigenesis

Summary

Introduction

The change of immune cell infiltration essentially influences the process of colorectal cancer development. Modeling the immune microenvironment of colorectal cancer by analyzing the genes involved can be more conducive to the in-depth understanding of carcinogenesis and the progression thereof. As a component of TME, immune and inflammatory cells have been shown to be closely associated with carcinogenesis. It is thought that chronic inflammation, tumor-related inflammatory responses, and inflammation in the tumor environment in the context of intestinal dysfunction contribute to the carcinogenesis of intestinal malignancies [7,8,9]. Immuno-inflammatory cell dynamics persist in the site of chronic inflammation, which has been proposed as the cradle for cancer development and progression [6, 10, 11]. The association between inflammation and immune cells can reflect the relationship of carcinogenesis and prognosis of patients [12]

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Conclusion