Ubiquitination-related biomarkers in metastatic melanoma patients and their roles in tumor microenvironment

转移性黑色素瘤患者泛素化相关生物标志物及其在肿瘤微环境中的作用

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作者:Li Zhang, Zhehao Shi, Fan Zhang, Bin Chen, Wei Qiu, Lei Cai, Xiaohua Lin

Background

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.

Conclusion

This study provides a novel and prospective strategy to improve the clinical survival of SKCM patients.

Methods

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 in vitro experiments.

Results

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.

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