ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicImmune-Related Biomarkers in Skin and Breast Cancer: Innovations in Immunological Diagnostics and TherapiesView all 10 articles
Identification and validation of prognostic genes and prognostic models associated with cutaneous melanoma and integrative stress response
Provisionally accepted
- 1Key Laboratory of Melanoma Research, The Third Affiliated Hospital of Kunming Medical University, Yunnan CancerHospital, Peking University Cancer Hospital Yunnan, Yunnan, China. 650000, Kunming, China
- 2Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 430048, Wuhan, China
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Background: Skin cutaneous melanoma (SKCM) is a highly invasive cancer with dismal prognosis. Integrated stress response (ISR) is associated with tumorigenesis and progression, but its relationship with SKCM prognosis is unclear. This research aimed to identify relevant prognostic genes for SKCM prognosis and treatment insights. Methods: Data were obtained from public databases. Differential expression and regression analyses were used to identify prognostic genes. Based on these genes and independent prognostic factors, risk models and nomograms were constructed to assess their clinical application potential in SKCM. Then, immune microenvironment changes in SKCM were explored according to risk-group grouping, providing a basis for stratified treatment decisions for SKCM patients. Finally, RT-qPCR was used to validate the results. Results: DTL, DTX3L, KCNMB1, NDRG1, GPX2, DERL3 and MBTPS2 were validated as prognostic genes. A risk model was constructed to classify patients into High Risk Group (HRG) and Low Risk Group (LRG), with high-risk SKCM patients having a higher mortality rate. A nomogram integrating clinical indicators was an effective SKCM survival prediction tool. The immune microenvironment differed significantly between risk groups, and most differentially infiltrated immune cells had higher infiltration levels in the Low Risk Group (LRG). Immunotherapy analysis suggested that the Low Risk Group (LRG) might benefit little from treatment, highlighting the need for stratified treatment of SKCM patients. RT-qPCR showed that prognostic genes were up-regulated in human melanoma cells compared to fibroblasts. Conclusion: The identification of ISR-featured prognostic genes and risk score stratification provide new insights into targeting SKCM and enhancing the efficacy of immunotherapy.
Keywords: Skin Cutaneous Melanoma1, integrated stress response2, prognosticmode3, immune micro-environment4, Immunohistochemistry5
Received: 20 Aug 2025; Accepted: 17 Nov 2025.
Copyright: © 2025 Zhang, Wang, Yin, Lei, Fu, Liang, Li and Li. 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:
Ruilei Li, lruilei@163.com
Ke Li, likelikelike@126.com
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