Identification of Essential Tumor-Infiltrating Immune Cells and Relevant Genes in Left-Sided and Right-Sided Colon Cancers

Chen Su; Zeyang Lin; Yongmei Cui; Jian-Chun Cai; Jingjing Hou

doi:10.3390/cancers14194713

Identification of Essential Tumor-Infiltrating Immune Cells and Relevant Genes in Left-Sided and Right-Sided Colon Cancers

Cancers (Basel). 2022 Sep 28;14(19):4713. doi: 10.3390/cancers14194713.

Authors

Chen Su^{1

2}, Zeyang Lin³, Yongmei Cui⁴, Jian-Chun Cai^{1

2}, Jingjing Hou^{1

2}

Affiliations

¹ Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361102, China.
² Institute of Gastrointestinal Oncology, School of Medicine, Xiamen University, Xiamen 361005, China.
³ Department of Pathology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361102, China.
⁴ Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.

Abstract

Backgrounds: Colorectal cancer is the third most prevalent cancer worldwide. A right-sided colon cancer patient typically has a worse prognosis than one who has a left-sided colon cancer. There is an unclear understanding of how left-sided colon cancer differs from right-sided colon cancer in tumor-infiltrating immune cells (TIICs) and relevant genes.

Methods: The Cancer Genome Atlas provided RNA-seq data and clinical information regarding colon adenocarcinoma. We conducted a single-sample gene set enrichment analysis (ssGSEA) to quantify the level of 24 immune cells infiltrating the tissues. Based on an analysis of univariate Cox regression, immune cell types associated with survival were identified. Weighted gene co-expression network analysis (WGCNA) was used to identify hub genes related to location and critical immune cells. Based on the Search Tool for the Retrieval of Interacting Genes (STRING), interaction potential was predicted among the hub genes. Hub genes that influence outcomes through immune infiltration were identified using the least absolute shrinkage and selection operator (LASSO). Then, we used the TISIDB database (a repository portal for tumor-immune system interactions) to validate the correlation between hub genes and immune cell infiltration. Finally, immunohistochemical assays were conducted to determine the levels of proteins expressed by critical TIICs and cancer cells.

Results: Colon cancers on the right side of the body had higher levels of myeloid-derived suppressor cells (MDSCs) than on the left side. There were three key genes: LCP1, ITGB2, and IKZF1. It was found that their expression was linked to poor prognosis and an increased level of MDSC infiltration. An immunohistochemical study confirmed these findings.

Conclusions: There is a higher rate of MDSC infiltration in right-sided colon cancer when compared with left-sided colon cancer. COAD outcomes are associated with changes in MDSC infiltration, and therefore LCP1, ITGB2, and IKZF1 may be novel targets for immunotherapy.

Keywords: IKZF1; ITGB2; LCP1; MDSC; colorectal cancer; immune infiltration.

Grants and funding

This work was supported by grants from the Foundation of Xiamen Municipal Bureau of Science and Technology (Grant No. 3502Z20214ZD1034), the Foundation of Fujian Provincial Department of Science and Technology (2022J011344), the National Natural Science Foundation of China (no. 81871979), the Natural Science Foundation of Fujian Province (no. 2021J02056), and the Medical and Health Sciences Foundation of Xiamen (nos. 3502Z20199171 and 3502Z20204002).