Integrated Analysis Reveals COL4A3 as a Novel Diagnostic and Therapeutic Target in UV-Related Skin Cutaneous Melanoma

Zuochao Yao, Lu Lu, Qianhui Xu, Shan Hua, Hui Wang, Hua Jiang Department of Plastic and Reconstructive Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of ChinaCorrespondence: Hui Wang; Hua Jiang, Department of Plastic and Reconstructive Surgery, Shanghai East Hospital, School of Medicine, Tongji University, 150 Jimo Road, Pudong New Area, Shanghai, 200092, People’s Republic of China, Email pathology2000@163.com; jianghua@tongji.edu.cnBackground: High levels of UV exposure are a significant factor that can trigger the onset and progression of SKCM. Moreover, this exposure is closely linked to the malignancy of the tumor and the prognosis of patients. Our objective is to identify a tumor biomarker database associated with UV exposure, which can be utilized for prognostic analysis and diagnosis and treatment of SKCM.Methods: This study used the weighted gene co-expression network analyses (WGCNA) and gene mutation frequency analyses to screen for UV-related target genes using the GSE59455 and the cancer genome atlas databases (TCGA). The prognostic model was created using Cox regression and least absolute shrinkage and selection operator analyses (LASSCO). Furthermore, in vitro experiments further validated that the overexpression or knockdown of COL4A3 could regulate the proliferation and migration abilities of SKMEL28 and A357 melanoma cells.Results: A prognostic model was created that included six genes with a high UV-related mutation in SKCM: COL4A3, CHRM2, DSC3, GIMAP5, LAMC2, and PSG7. The model had a strong patient survival correlation (P˂0.001, hazard ratio (HR) = 1.57) and significant predictor (P˂0.001, HR = 3.050). Furthermore, the model negatively correlated with immune cells, including CD8+ T cells (Cor=− 0.408, P˂0.001), and M1-type macrophages (Cor=− 0.385, P˂0.001), and immune checkpoints, including programmed cell death ligand-1. Moreover, we identified COL4A3 as a molecule with si