Identification and validation of a TTN-associated immune prognostic model for skin cutaneous melanoma

Qirui Wang; Xingtai Huang; Siyi Zeng; Renpeng Zhou; Danru Wang

doi:10.3389/fgene.2022.1084937

Frontiers in Genetics (Jan 2023)

Identification and validation of a TTN-associated immune prognostic model for skin cutaneous melanoma

Qirui Wang,
Xingtai Huang,
Siyi Zeng,
Renpeng Zhou,
Danru Wang

Affiliations

Qirui Wang: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Xingtai Huang: Shanghai Key Laboratory of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Orthodontics, College of Stomatology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Siyi Zeng: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Renpeng Zhou: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Danru Wang: Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

DOI: https://doi.org/10.3389/fgene.2022.1084937
Journal volume & issue: Vol. 13

Abstract

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TTN is the most commonly mutated gene in skin cutaneous melanoma (SKCM). Tumor mutational burden (TMB) can generate new antigens that regulate the recognition of T cells, which will significantly affect the prognosis of patients. The TTN gene has a long coding sequence and a high number of mutant sites, which allows SKCM patients to produce higher TMB and may influence the immune response. It has been found that the overall survival (OS) of SKCM patients with TTN mutation was significantly higher than that of wild-type patients. However, the effect of TTN mutation on the immune microenvironment of SKCM has not been fully investigated. Here, we systematically explored the relationship and potential mechanisms between TTN mutation status and the immune response. We first revealed that TTN mutated SKCM were significantly associated with four immune-related biological processes. Next, 115 immune genes differentially expressed between TTN mutation and wild-type SKCM patients were found to significantly affect the OS of SKCM patients. Then, we screened four immune-related genes (CXCL9, PSMB9, CD274, and FCGR2A) using LASSO regression analysis and constructed a TTN mutation-associated immune prognostic model (TM-IPM) to distinguish the SKCM patients with a high or low risk of poor prognosis, independent of multiple clinical characteristics. SKCM in the low-risk group highly expressed a large number of immune-related genes, and functional enrichment analysis of these genes showed that this group was involved in multiple immune processes and pathways. Furthermore, the nomogram constructed by TM-IPM with other clinicopathological parameters can provide a predictive tool for clinicians. Moreover, we found that CD8+ T cells were significantly enriched in the low-risk group. The expression level of immune checkpoints was higher in the low-risk group than in the high-risk group. Additionally, the response to chemotherapeutic agents was higher in the low-risk group than in the high-risk group, which may be related to the long survival in the low-risk group. Collectively, we constructed and validated a TM-IPM using four immune-related genes and analyzed the potential mechanisms of TM-IPM to predict patient prognosis and response to immunotherapy from an immunological perspective.

Published in Frontiers in Genetics

ISSN: 1664-8021 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Biology (General): Genetics
Website: http://journal.frontiersin.org/journal/genetics

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