CSMD3 is Associated with Tumor Mutation Burden and Immune Infiltration in Ovarian Cancer Patients

Abstract

Nan Lu,1,* Jinhui Liu,2,* Mengting Xu,2,* Jianqiang Liang,2 Yichun Wang,3 Zhipeng Wu,4 Yan Xing,2 Feiyang Diao1 1Department of Reproduction, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People’s Republic of China; 3Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People’s Republic of China; 4Department of Urology, The Affiliated Sir Run Run Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feiyang DiaoDepartment of Reproduction, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaEmail [email protected] XingDepartment of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People’s Republic of ChinaEmail [email protected]: Globally, ovarian cancer (OC), the deadliest gynecologic malignancy, remains a major cause of mortality, with a rising number of cases in many low- and middle-income countries. Immunotherapy has been proven to be promising for OC. There is increasing awareness of the vital role that tumor mutation burden (TMB) plays in predicting the efficacy of immunotherapy. Women with a family history of OC are at higher risk of the disease due to gene mutations. However, whether these gene mutations are related to immune response and TMB remains to be explored.Methods: Our present work analyzed genetic mutation data of OC patients obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) cohorts, and we identified 11 frequently mutated genes, namely, APOB, CSMD3, DST, FAT3, FLG, HMCN1, MUC16, RYR1, TP53, TTN, and USH2A, in accordance with the overlap of two databases.Results: A statistically higher TMB was detected by whole-exome sequencing in patients with OC with CSMD3 mutation than in those with mutations in the other frequently mutated genes. Prognosis analysis performed with patients from the TCGA cohort revealed that those with CSMD3 mutation had an overall survival (OS) that was inferior to that of those with wild-type CSMD3. Gene set enrichment analysis (GSEA) and CIBERSORT analysis indicated that OC samples with CSMD3 mutations had significant involvement of pathways related to the immune response.Conclusion: In summary, we found that CSMD3 mutation is highly correlated with increased TMB and poor clinical prognosis and that it might function as a biomarker for predicting prognosis and choosing an immunotherapy regimen.Keywords: ovarian cancer, CSMD3, tumor mutation burden, prognosis, tumor-infiltrating immune cells

Keywords

• ovarian cancer
• csmd3
• tumor mutation burden
• prognosis
• tumor-infiltrating immune cells