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ORIGINAL RESEARCH article

Front. Oncol.

Sec. Skin Cancer

Volume 15 - 2025 | doi: 10.3389/fonc.2025.1485006

This article is part of the Research TopicGenetics and Epigenetics of Melanoma and Non-Melanoma Skin CancerView all 5 articles

Developing a prognostic model of glutamine metabolism-related genes associated with clinical features and immune status in melanoma

Provisionally accepted
Hongyan  HuHongyan Hu1*Jing  YangJing Yang2Jin  MiaoJin Miao3Chen  LiChen Li1Cao  WangCao Wang1Fengming  RanFengming Ran1Jie  ZouJie Zou1Yi  ZhangYi Zhang1Liufang  ZhaoLiufang Zhao1Wentao  ZhaoWentao Zhao1Conghui  AiConghui Ai1*
  • 1Yunnan Cancer Hospital, Kunming, Yunnan Province, China
  • 2The First People’s Hospital of Yunnan Province, Kunming, Yunnan Province, China
  • 3Department of Pathology, Yunnan Cancer Hospital, Kunming, China

The final, formatted version of the article will be published soon.

Abstract: Melanoma exhibited a poor prognosis due to its aggression and heterogeneity. The effect of glutamate metabolism promoting tumor progression on cutaneous melanoma remains unknown. Herein, glutamine metabolism-related genes (GRGs) were identified followed by constructing a prognostic model for melanoma via bioinformatics analysis. Patient data were collected from ,Gene Expression Omnibus (GEO) and The Cancer Genome Atlas—Skin Cutaneous Melanoma (TCGA-SKCM). In addition, GRGs were extracted from the MSigDB database, and the R package "Seurat" was used for scRNA-seq data processing. Therefore, eight key genes (CHMP4A, IFFO1, ANKRD10, ZDHHC11, CLPB, ANKMY1, TCAP and POLG2) were identified to construct a risk model. Based on univariate and multivariate Cox regression analyses, clinical characteristics including Clark stage and ulcer status were identified as independent prognostic factors, and a nomogram was successfully constructed. Survival analysis demonstrated that the overall survival rates of the high-risk group were lower than those of the low-risk group. The gene set enrichment analysis (GSEA) results showed that only ANKRD10, ANKMY1 and TCAP were enriched in the “glycolysis gluconeogenesis” pathway. The high-risk and low-risk groups displayed significant differences in immune cell infiltration and immune checkpoint expression. Analysis on drug sensitivity revealed that the high-risk group was highly sensitive to rapamycin. Additionally, it was verified that IFFO1, ANKRD10 and POLG2 were markedly upregulated and CHMP4A was also markedly downregulated in A375 cells by RT-PCR, which was consistent with the partial results of biological analysis. Overall, it would provide valuable information about the GRGs of prognosis and immune status in melanoma.

Keywords: glutamine metabolism, Melanoma, prognosis, immune microenvironment, bioinformatics

Received: 23 Aug 2024; Accepted: 31 Jul 2025.

Copyright: © 2025 Hu, Yang, Miao, Li, Wang, Ran, Zou, Zhang, Zhao, Zhao and Ai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Hongyan Hu, Yunnan Cancer Hospital, Kunming, Yunnan Province, China
Conghui Ai, Yunnan Cancer Hospital, Kunming, Yunnan Province, China

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