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ORIGINAL RESEARCH ARTICLE

Autophagy-related-gene signature predicts survival outcomes and the tumor immune landscape in skin cutaneous melanoma

Yadong Xue1,2 ,  Yunjin Xie2,3,4,5,6 ,  Xiyuan Zhang2,3,4,5,6* ,  Mingzhu Yin2,3,4,5,6*
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1 Dermatology Department, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
2 Clinical Research Center, Medical Pathology Center, Cancer Early Detection and Treatment Center, and Translational Medicine Research Center, Chongqing University Three Gorges Hospital, Chongqing University, Chongqing, China
3 Chongqing Technical Innovation Center for Quality Evaluation and Identification of Authentic Medicinal Herbs, Chongqing, China
4 Chongqing University Three Gorges Hospital and Academy for Advanced Interdisciplinary Technology, Chongqing University Ferenc Krausz Nobel Laureate Scientific Workstation, Chongqing, China
5 School of Medicine, Chongqing University, Chongqing, China
6 Institute of Advanced Interdisciplinary Studies, Chongqing University, Chongqing, China
EJMO, 025370399 https://doi.org/10.36922/EJMO025370399
Received: 14 September 2025 | Revised: 5 November 2025 | Accepted: 2 December 2025 | Published online: 12 August 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Skin cutaneous melanoma (SKCM) is a malignant skin cancer characterized by heterogeneous outcomes. Autophagy exerts dual effects on tumor progression and immune modulation.

Objective: This study aims to investigate whether autophagy-related genes can stratify melanoma patients with different prognoses and to examine their association with the immune microenvironment.

Methods: We identified 371 autophagy-related genes from the Human Autophagy Database and analyzed transcriptomic and clinical data from 405 SKCM cases from The Cancer Genome Atlas (TCGA). An autophagy-based prognostic signature was initially screened by univariate Cox regression and then refined using Least Absolute Shrinkage and Selection Operator Cox regression. Risk scores derived from this signature classified patients into high- and low-risk groups, and the predictive power of the signature was validated in TCGA and Gene Expression Omnibus datasets. Functional enrichment, differential expression, and immune deconvolution analyses (Cell-type Identification by Estimating Relative Subsets of Known RNA Transcripts) were used to explore molecular and immune differences between groups.

Results: We constructed a 102-autophagy-related-gene signature, which robustly stratifies patients with distinct survival outcomes in different cohorts. Low-risk tumors exhibited immune-activating transcriptional programs and higher infiltration of cluster of differentiation (CD)8+ T lymphocytes, natural killer cells, plasma cells, and memory CD4+ T lymphocytes. High-risk tumors were associated with oncogenic signaling pathways and immunosuppressive subsets, such as M2 macrophages and Tregs. Canonical immune checkpoints, including PDCD1, CD274, CTLA4, LAG3, and TIGIT, were upregulated in the low-risk group and correlated significantly with effector immune infiltration, presenting an “immune-inflamed” phenotype.

Conclusion: This autophagy-related-gene signature distinguished prognostic subgroups and highlighted biological and immune diversity in melanoma, providing potential directions for future autophagy research.

Keywords
Skin cutaneous melanoma
Autophagy
Immune microenvironment
Prognostic signature
Checkpoint blockade
Funding
This study is jointly supported by Natural Science Foundation of the New Era Longjiang Outstanding Master’s and Doctoral Dissertation Funding Program (Grant No.LJYXL2022-074), The Scientific Research and Innovation Foundation of The First Affiliated Hospital of Harbin Medical University (Grant No.2023M30), National Key R&D Programmes (NKPs) of China (Grant No. 2022YFC3601800), and General project of Chongqing Joint Fund of Science and Technology (Grant No. CSTB2024NSCQ-LMX0016).
Conflict of interest
Mingzhu Yin is the Editor-in-Chief of this journal, but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
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