Key Markers Involved in the Anticolon Cancer Response of CD8+ T Cells through the Regulation of Cholesterol Metabolism

Liang Dong; Xi Yang; Yangyanqiu Wang; Yin Jin; Qing Zhou; Gong Chen; Shuwen Han

doi:10.1155/2021/9398661

Key Markers Involved in the Anticolon Cancer Response of CD8+ T Cells through the Regulation of Cholesterol Metabolism

J Oncol. 2021 Nov 23:2021:9398661. doi: 10.1155/2021/9398661. eCollection 2021.

Authors

Liang Dong¹, Xi Yang², Yangyanqiu Wang³, Yin Jin⁴, Qing Zhou⁵, Gong Chen⁶, Shuwen Han⁷

Affiliations

¹ Department of Gastroenterology, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Sanhuan North Road No. 1558, Wuxing District, Huzhou 313000, Zhejiang, China.
² Department of Intervention and Radiotherapy, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou 313000, Zhejiang, China.
³ Graduate School of Medical College of Zhejiang University, Kaixuan Road No. 268, Jianggan District, Hangzhou 310029, Zhejiang, China.
⁴ Department of Laboratory Medicine, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou 313000, Zhejiang, China.
⁵ Department of Nursing, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Sanhuan North Road No.1558, Wuxing District, Huzhou 313000, Zhejiang, China.
⁶ Undergraduate School of Clinic Medicine, Huzhou University, Huzhou 313000, Zhejiang, China.
⁷ Department of Oncology, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou 313000, Zhejiang, China.

Abstract

Background: T cell-mediated antitumor immune response is the basis of colorectal cancer (CRC) immunotherapy. Cholesterol plays an important role in T cell signal transduction and function. Apolipoprotein E (APOE) plays a major role in cholesterol metabolism.

Objective: To screen and analyze key markers involved in the anticolon cancer response of CD8+ T cells through the regulation of cholesterol metabolism.

Methods: Based on the median cutoff of the expression value of APOE according to the data downloaded from The Cancer Genome Atlas and Gene Expression Omnibus database, patients were grouped into low and high expression groups. Differences in clinical factors were assessed, and survival analysis was performed. Differentially expressed genes (DEGs) in the high and low expression groups were screened, followed by the analysis of differences in tumor-infiltrating immune cells and weighted gene coexpression network analysis results. The closely related genes to APOE were identified, followed by enrichment analysis, protein-protein interaction (PPI) network analysis, and differential expression analysis. Immunohistochemical staining (IHC) was used to detect the expression of CD8 in CRC tissues.

Results: There were significant differences in prognosis and pathologic_N between the APOE low and high expression groups. A total of 2,349 DEGs between the high and low expression groups were selected. A total of 967 genes were obtained from the blue and brown modules. The probability of distribution of CD8+ T cells differed significantly between the two groups, and 320 closely related DEGs of APOE were screened. Genes including the HLA gene family, B2M, IRF4, and STAT5A had a higher degree in the PPI network. GEO datasets verified the prognosis and the related DEGs of APOE. IHC staining verified the relationship between the distribution of CD8+ T cells and APOE expression.

Conclusion: Genes including the HLA gene family, B2M, IRF4, and STAT5A might be the key genes involved in the anticolon cancer response of CD8+ T cells through the regulation of cholesterol metabolism.