Construction of a prognostic model for colorectal adenocarcinoma based on Zn transport-related genes identified by single-cell sequencing and weighted co-expression network analysis

Hua Chen; Ting Zhao; Jianing Fan; Zhiqiang Yu; Yiwen Ge; He Zhu; Pingping Dong; Fu Zhang; Liang Zhang; Xiangyang Xue; Xiaoming Lin

doi:10.3389/fonc.2023.1207499

Construction of a prognostic model for colorectal adenocarcinoma based on Zn transport-related genes identified by single-cell sequencing and weighted co-expression network analysis

Front Oncol. 2023 Sep 26:13:1207499. doi: 10.3389/fonc.2023.1207499. eCollection 2023.

Authors

Hua Chen¹, Ting Zhao², Jianing Fan³, Zhiqiang Yu⁴, Yiwen Ge³, He Zhu¹, Pingping Dong¹, Fu Zhang¹, Liang Zhang⁴, Xiangyang Xue², Xiaoming Lin¹

Affiliations

¹ Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
² Department of Microbiology and Immunology, School of Basic Medical Science, Institute of Molecular Virology and Immunology, Institute of Tropical Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China.
³ School of Second Clinical Medical, Wenzhou Medical University, Wenzhou, Zhejiang, China.
⁴ Department of General Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Abstract

Background: Colorectal cancer (CRC) is one of the most prevalent malignancies and the third most lethal cancer globally. The most reported histological subtype of CRC is colon adenocarcinoma (COAD). The zinc transport pathway is critically involved in various tumors, and its anti-tumor effect may be through improving immune function. However, the Zn transport pathway in COAD has not been reported.

Methods: The determination of Zn transport-related genes in COAD was carried out through single-cell analysis of the GSE 161277 obtained from the GEO dataset. Subsequently, a weighted co-expression network analysis of the TCGA cohort was performed. Then, the prognostic model was conducted utilizing univariate Cox regression and least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Functional enrichment, immune microenvironment, and survival analyses were also carried out. Consensus clustering analysis was utilized to verify the validity of the prognostic model and explore the immune microenvironment. Ultimately, cell experiments, including CCK-8,transwell and scratch assays, were performed to identify the function of LRRC59 in COAD.

Results: According to the Zn transport-related prognostic model, the individuals with COAD in TCGA and GEO databases were classified into high- and low-risk groups. The group with low risk had a comparatively more favorable prognosis. Two groups had significant variations in the immune infiltration, MHC, and the expression of genes related to the immune checkpoint. The cell experiments indicated that the proliferation, migration, and invasion of the HCT-116, DLD-1, and RKO cell lines were considerably increased after LRRC59 knockdown. It proved that LRRC59 was indeed a protective factor for COAD.

Conclusion: A prognostic model for COAD was developed using zinc transport-related genes. This model can efficiently assess the immune microenvironment and prognosis of individuals with COAD. Subsequently, the function of LRRC59 in COAD was validated via cell experiments, highlighting its potential as a biomarker.

Keywords: Immune infiltration; Zn transport; colon adenocarcinoma (COAD); colorectal cancer (CRC); immune microenvironment; immune microenvironment Colon adenocarcinoma (COAD); prognostic.

Grants and funding

This research was supported by Zhejiang Provincial Science and Technology Innovation Program (New Young Talent Program) for College Students (Grant No. 2023R413028).