Comparative transcriptomic analysis reveals differences in gene expression and regulatory pathways between nonacral and acral melanoma in Asian individuals

Abstract

Melanoma predominantly occurs in White individuals, which is associated with factors such as exposure to UV radiation and skin pigmentation. Despite its low incidence, melanoma is the primary cause of skin cancer–related death in Asia, typically in areas with low sun exposure. In our previous whole‐exome sequencing study, we identified mutational signature 12 as the most prevalent variant in Asian patients, differing from the common UV‐associated mutational signature 7 observed in White individuals. We also observed major differences between acral melanoma (AM) and nonacral melanoma (NAM) in terms of signatures 7, 21, and 22. Notably, few studies have investigated the genomic differences between AM and NAM in Asian individuals. Therefore, in this study, we conducted transcriptomic sequencing to examine the disparities in RNA expression between AM and NAM. Ribosomal RNA depletion was performed to enhance the detection of functionally relevant coding and noncoding transcripts. Ingenuity pathway analysis revealed significant differences in gene expression and regulatory pathways between AM and NAM. The results also indicate that the genes involved in cell cycle signaling or immune modulation and programmed cell death protein 1/programmed cell death 1 ligand 1 signaling were differentially expressed in NAM and AM. In addition, high CDK4 expression and cell cycle variability were observed in AM, with high immunogenicity in NAM. Overall, these findings provide further insights into the pathogenesis of melanoma and serve as a reference for future research on this major malignant disease.

Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling

“…Acral melanomas, having no direct association with sun exposure, although having mutations in BRAF , NRAS , NF1 , and KIT , show a lighter and different mutational burden in comparison to low-CSD or high-CSD melanomas [ 6 , 10 , 31 , 32 , 79 , 133 , 134 , 135 , 136 ]. In addition, recent transcriptomic analysis showed significant differences in gene expression and regulatory pathways between acral and non-acral melanomas in an Asian population [ 35 ].…”

“…According to the recent World Health Organization (WHO) classification, melanomas are subdivided etiologically into those related to sun exposure and those that are not, with the former stratified according to cumulative solar damage (CSD) of the skin into low- and high-CSD melanomas [ 2 , 21 , 30 ]. Melanomas of which the etiology is predominantly unrelated to sun exposure include mucosal, acral, uveal and Spitzoid melanomas, melanomas arising in blue or congenital nevi, and rare melanomas arising in the CNS [ 7 , 21 , 25 , 27 , 31 , 32 , 33 , 34 , 35 ]. In this review, we will focus on melanomas related to sun exposure, including melanomas with low CSD, such as superficial spreading type and nodular melanomas, and with high CSD, such as the lentigo maligna type and desmoplastic melanomas [ 21 , 30 , 36 , 37 ].…”