CSMD1 Mutation Related to Immunity Can Be Used as a Marker to Evaluate the Clinical Therapeutic Effect and Prognosis of Patients with Esophageal Cancer

Xin Fan; Jianxiong Song; Yating Fan; Jiaqi Li; Yutao Chen; Huanhuan Zhu; Zhiyuan Zhang

doi:10.2147/IJGM.S338284

CSMD1 Mutation Related to Immunity Can Be Used as a Marker to Evaluate the Clinical Therapeutic Effect and Prognosis of Patients with Esophageal Cancer

Int J Gen Med. 2021 Nov 23:14:8689-8710. doi: 10.2147/IJGM.S338284. eCollection 2021.

Authors

Xin Fan¹, Jianxiong Song¹, Yating Fan¹, Jiaqi Li², Yutao Chen¹, Huanhuan Zhu¹, Zhiyuan Zhang¹

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, The First Clinical Medical College of Nanchang University, Nanchang, 330000, People's Republic of China.
² School of Stomatology, Nanchang University, Nanchang, 330000, People's Republic of China.

Abstract

Introduction: As a highly aggressive tumor with a poor prognosis, esophageal cancer (ESCA)'s relationship with gene mutations is unclear. Therefore, we tried to explore the role of gene mutation in ESCA progression and its relationship with immune response, clinical treatment, and prognosis.

Methods: In addition to copy number variation (CNV) situations of common genes obtained from 2 public databases, the relationship between mutations and prognosis/tumor mutational burden (TMB) was also analyzed. Kaplan-Meier survival and Cox regression analysis were used to identify the CSMD1 mutation status as an independent predictor of prognosis. We also enriched related functions and pathways. Next, the relationship between 22 immune cells and CSMD1 mutation status was analyzed. In addition to the differences in the expression levels of immune checkpoint inhibitors (ICIs)-related genes between the high TMB and low TMB groups, the differences in the expression levels of ICIs/m6a/multi-drug resistance-related genes and the sensitivity of three chemotherapeutic drugs between CSMD1 mutant and the wild group were also compared. In addition to differences and prognostic analysis of CSMD1 expression, the correlation analysis between the expression of these genes/immune cells and the expression of CSMD1 was also performed. Finally, a nomogram that could efficiently and conveniently predict the survival probability of ESCA patients was constructed and verified.

Results: We obtained 17 frequently mutated genes distribution. Mutation and loss of CSMD1 are frequent in ESCA. Only CSMD1 mutation can be used as an independent predictor of poor prognosis. Patients in the high TMB group have a lower survival probability. Wild CSMD1 may be involved in immune-related pathways. More helper T cells and fewer resting state dendritic cells were found in the CSMD1 mutant group. The PD-1 expression in the high TMB group showed higher. Paclitaxel sensitivity and ABCC1 expression were higher in the wild CSMD1 group. Most cancers show differential expression of CSMD1. Except for the prognosis of ESCA, the expression of CSMD1 is related to immune cell content and the expression of ICIs/m6a/multi-drug resistance related genes.

Discussion: CSMD1 mutation could be used as an immune-related biomarker to predict prognosis and treatment effect of paclitaxel. Mutation and loss of CSMD1 may promote the progression of ESCA.

Keywords: CSMD1; TMB; esophageal cancer; prognosis; tumor-infiltrating immune cells.

Grants and funding

The study was supported by the Research Fund Project of Jiangxi Provincial Department of Education (180017).