Research Paper Volume 16, Issue 11 pp 9692—9708
Prognostic and therapeutic roles of SETD2 in cutaneous melanoma
- 1 Department of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China
- 2 Cancer Bio-immunotherapy Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China
- 3 Medical Research Center, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, China
- 4 NHC Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate, Fujian Maternity and Child Health Hospital, Fuzhou, Fujian, China
- 5 Department of Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, Fujian, China
- 6 Department of Pharmacology, QuanZhou Women’s and Children’s Hospital, Quanzhou, Fujian, China
- 7 College of Chemistry, Fuzhou University, Fuzhou, China
Received: September 18, 2023 Accepted: April 16, 2024 Published: June 5, 2024
https://doi.org/10.18632/aging.205894How to Cite
Copyright: © 2024 Xiong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Cutaneous melanoma (CM) is an aggressive form of skin cancer with limited treatment options for advanced stages. Prognostic markers that accurately predict patients’ outcomes and guide therapeutic strategies are crucial for improving melanoma management. SETD2 (SET Domain-Containing Protein 2), a histone methyltransferase involved in chromatin remodeling and gene regulation, has recently emerged as a tumor suppressor. Its dysfunction is involved in oncogenesis in some cancers, but little is known about its functions in progression and therapeutic response of melanoma.
Methods: RNA-seq and clinical data from public database were used to evaluate the survival analysis, gene set enrichment, IC50 of therapeutics and immunotherapy response. SETD2 knock-out A375 cell line (A375SETD2ko) was developed by Crispr/cas9 and CCK-8 analysis and nude mice used to evaluate the proliferation and invasion of melanoma cells in vitro and in vivo, while Western blotting tested the MMR-related protein.
Results: SETD2 was commonly down-regulated in melanoma samples which demonstrated an unfavorable survival. Cells without SETD2 expression tend to have a more progressive and invasive behavior, with resistance to chemotherapy. However, they are more sensitive to tyrosine kinase inhibitors (TKIs). They also exhibit inflamed features with lower TIDE (Tumor Immune Dysfunction and Exclusion) score and higher tumor mutation burden (TMB), showing that these patients may benefit from immunotherapy.
Conclusions: This study revealed that SETD2 dysfunction in melanoma implied a poor prognosis and chemotherapy resistance, but highly sensitive to TKIs and immunotherapy, highlighting the prognostic and therapeutic value of SETD2 in cutaneous melanoma.