Yi Zhang,1,* Ansheng Xie,2,* Di Wang,2 Weiwei Deng2 

1Department of Dermatology, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, People’s Republic of China; 2Dermatology Hospital of Southern Medical University, Zhou Guang, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Weiwei Deng; Di Wang, Email dengww@smu.edu.cn; 602619666@qq.com

Background: Skin cutaneous melanoma (SKCM) ranks among the most prevalent malignant tumors, highlighting the significance of identifying new research targets. In this study, our objective was to pinpoint pivotal genes implicated in SKCM pathogenesis and ascertain their potential as prognostic biomarkers.
Methods: Leveraging data from 1809 normal skin samples and 471 SKCM samples, we identified differentially expressed genes (DEGs). Using a comprehensive suite of bioinformatic analyses, including weighted gene co-expression network analysis (WGCNA), we elucidated the functions of these DEGs and singled out hub genes. Cox analyses and overall survival analyses underscored that elevated expression of these genes correlated with more favorable prognoses.
Results: Ultimately, we identified five genes (PLAC8, IL4I1, ZNF80, CCR8, CLEC4C) as novel prognostic markers for SKCM. Furthermore, multivariate Cox analyses pinpointed ZNF80 and CCR8 as independent prognostic biomarkers. Experimental validation targeting these genes revealed significant downregulation in melanoma cells, except for CCR8. Subsequent knockdown of IL4I1 promoted both the proliferation and inhibited the apoptosis of melanoma cells.
Conclusion: In summary, our study identified a series of potential prognostic genes in melanoma and verified the functional role of IL4I1 among them.

Keywords: skin cutaneous melanoma, prognostic biomarkers, IL4I1, ZNF80, CCR8