Zhang Li, Shi Zhehao, Zhang Fan, Chen Bin, Qiu Wei, Cai Lei, Lin Xiaohua
Department of Dermatology and Venereology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Front Oncol. 2023 May 19;13:1170190. doi: 10.3389/fonc.2023.1170190. eCollection 2023.
Skin cutaneous melanoma (SKCM) is the deadliest type of cutaneous malignancy. Ubiquitination is a process of protein sorting and degradation that exhibits multiple functions in the progression of various tumors. This study aimed to characterize a set of genes for ubiquitination in SKCM.
The expression patterns of ubiquitin-associated genes (URGs) and the corresponding clinical information in SKCM tissues were comprehensively analyzed based on The Cancer Genome Atlas (TCGA) database. We performed univariate and multivariate Cox proportional regression models to characterize the risk scores and identify four critical genes related to prognostic ubiquitination (HCLS1, CORO1A, NCF1 and CCRL2), which were used to construct the prognostic signatures. We also studied the effects of HCLS1, CORO1A and CCRL2 on tumor metastasis-related indicators at the cellular level through experiments.
SKCM patients in the low-risk group showing a longer survival than those in the high-risk group. Characteristic risk scores correlated with several clinicopathological variables and reflected the infiltration of multiple immune cells. In addition, the knockdown of CLS1, CORO1A and CCRL2 affected cellular malignant biological behavior through the EMT signaling pathway.
This study provides a novel and prospective strategy to improve the clinical survival of SKCM patients.
皮肤黑色素瘤（SKCM）是最致命的皮肤恶性肿瘤类型。泛素化是一种蛋白质分选和降解过程，在各种肿瘤进展中发挥多种功能。本研究旨在鉴定一组SKCM中泛素化相关基因。
基于癌症基因组图谱（TCGA）数据库全面分析SKCM组织中泛素相关基因（URGs）的表达模式及相应临床信息。我们进行单因素和多因素Cox比例回归模型以表征风险评分并鉴定四个与预后泛素化相关的关键基因（HCLS1、CORO1A、NCF1和CCRL2），这些基因用于构建预后特征。我们还通过实验在细胞水平研究了HCLS1、CORO1A和CCRL2对肿瘤转移相关指标的影响。
低风险组的SKCM患者比高风险组患者生存期更长。特征性风险评分与多个临床病理变量相关，并反映多种免疫细胞的浸润情况。此外，敲低CLS1、CORO1A和CCRL2通过EMT信号通路影响细胞恶性生物学行为。
本研究为改善SKCM患者临床生存期提供了一种新的前瞻性策略。
