Prognostic Model and Tumor Immune Microenvironment Analysis of Complement-Related Genes in Gastric Cancer

Xianhua Gu; Honghong Shen; Guangzheng Zhu; Xinwei Li; Yue Zhang; Rong Zhang; Fang Su; Zishu Wang

doi:10.2147/JIR.S422903

Prognostic Model and Tumor Immune Microenvironment Analysis of Complement-Related Genes in Gastric Cancer

J Inflamm Res. 2023 Oct 18:16:4697-4711. doi: 10.2147/JIR.S422903. eCollection 2023.

Authors

Xianhua Gu^#¹, Honghong Shen^#², Guangzheng Zhu³, Xinwei Li², Yue Zhang², Rong Zhang¹, Fang Su², Zishu Wang²

Affiliations

¹ Department of Gynecology Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People's Republic of China.
² Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People's Republic of China.
³ Department of Surgical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People's Republic of China.

^# Contributed equally.

Abstract

Introduction: The complement system is integral to the innate and adaptive immune response, helping antibodies eliminate pathogens. However, the potential role of complement and its modulators in the tumor microenvironment (TME) of gastric cancer (GC) remains unclear.

Methods: This study assessed the expression, frequency of somatic mutations, and copy number variations of complement family genes in GC derived from The Cancer Genome Atlas (TCGA). Lasso and Cox regression analyses were conducted to develop a prognostic model based on the complement genes family, with the training and validation sets taken from the TCGA-GC cohort (n=371) and the International Gene Expression Omnibus (GEO) cohort (n=433), correspondingly. The nomogram assessment model was used to predict patient outcomes. Additionally, the link between immune checkpoints, immune cells, and the prognostic model was investigated.

Results: In contrast to patients at low risk, those at high risk had a less favorable outcome. The prognostic model-derived risk score was shown to serve as a prognostic marker of GC independently, as per the multivariate Cox analysis. Nomogram assessment showed that the model had high reliability for predicting the survival of patients with GC in the 1, 3, 5 years. Additionally, the risk score was positively linked to the expression of immune checkpoints, notably CTLA4, LAG3, PDCD1, and CD274, according to an analysis of immune processes. The core gene C5aR1 in the prognostic model was found to be upregulated in GC tissues in contrast to adjoining normal tissues, and patients with elevated expressed levels of C5aR1 had lower 10-year overall survival (OS) rates.

Conclusion: Our work reveals that complement genes are associated with the diversity and complexity of TME. The complement prognosis model help improves our understanding of TME infiltration characteristics and makes immunotherapeutic strategies more effective.

Keywords: complement genes; gastric cancer; immune checkpoints; prognostic model; tumor microenvironment.

Grants and funding

The present study was supported by the College Student Innovation Training Program of Bengbu Medical College (grant no. Byycx 22110), 512 Talent Cultivation Plan of Bengbu Medical College (grant numbers by51201319), Research and Innovation Team of Bengbu Medical College (grant no. BYKC201908). University Scientific research project of Education Department of Anhui Province (grant no. KJ2021A0714). Provincial education and Teaching research project (grant no. 2021jyxm0954).