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Updated: Jan 11, 2026
A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
Constructing a novel MPT-driven necrosis-associated gene set for predicting prognosis and immune status in skin
1Department of Plastic and Cosmetic Surgery, Wuxi No. 2 People's Hospital, Jiangnan University Medical Center, Wuxi, Jiangsu Province, China.
Background:
Skin cutaneous melanoma (SKCM) is an aggressive malignancy with limited prognostic markers. Mitochondrial permeability transition (MPT)-driven necrosis has been implicated in tumor progression and immune regulation, yet its role in SKCM remains unclear.
Methods:
39 MPT-driven necrosis-related genes (MPTDNRG) were retrieved from Molecular Signatures Database (MSigDB). Using TCGA-SKCM and GTEx datasets, differentially expressed genes (DEGs) were identified and incorporated into Cox and LASSO analyses. An MPT-driven necrosis-related gene signature (MPTDNRGS) was constructed. The signature was validated in GEO cohorts (GSE19234, GSE65904). A nomogram integrating clinical factors was established to assess predictive performance. Functional enrichment, immune infiltration, and checkpoint responsiveness were evaluated. Single-cell RNA-seq (scRNA-seq) datasets were further analyzed to map cell-type-specific expression and T-cell trajectories.
Results:
A five gene signature (BIRC3, CASP7, ENDOG, PRF1, PRKCB) stratified patients into high and low risk groups with distinct survival outcomes. The nomogram achieved strong predictive accuracy (3-year AUC = 0.772). High risk patients exhibited suppressed immune activation, lower T-cell infiltration, and reduced predicted response to immune checkpoint inhibitors. Single cell analysis revealed higher MPTDNRGS scores in tumor-infiltrating T cells than in normal controls. Pseudotime trajectories showed cytotoxic T cells transitioning to immunosuppressive phenotypes, marked by progressive BIRC3 upregulation. Elevated BIRC3 correlated with immune inhibitory markers and enrichment of TGF-β and IL6/JAK/STAT3 pathways.
Conclusion:
We established and validated a novel MPT-driven necrosis-based prognostic model for SKCM. This model reliably predicted patient outcomes and immune status. BIRC3 emerged as a potential regulator of T-cell dysfunction and a promising therapeutic target in SKCM.
