Evidence map›Paper›PMID 40755114›Full record

ArticleCurrent topics in medicinal chemistry2026

Preliminary Study on GZMA- and GSDMB-Associated Pyroptosis and CD8+ T Cell-Mediated Immune Evasion in Skin Cutaneous Melanoma.

Jianqin Chen, Zhirong Huang, Fengfeng Xie, Jing Liu, Wen Sun, Jingli Xu, Wenfang Xie

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Article in Current topics in medicinal chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1 citing paper in PubMed.

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5 · Who and what money

Authors and funding

7 authors.

Jianqin ChenDepartment of Dermatology, Guangdong Second Traditional Chinese Medicine Hospital, Guangzhou, 510530, China.
Zhirong HuangDepartment of Dermatology, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, 361009, China.
Fengfeng XieDepartment of Radiology, Quanzhou Women's and Children's Hospital, Quanzhou, 362000, China.
Jing LiuDepartment of Dermatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou 510000, China.
Wen SunDepartment of Dermatology, Jingmen Central Hospital, Jingmen 448000, China.
Jingli XuDepartment of Orthopedics, Zhanjiang First Hospital of Traditional Chinese Medicine, Zhanjiang 524000, China.
Wenfang XieDepartment of Respiratory Medicine, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou, 510315, China.

Funding

Guangdong Basic and Applied Basic Research Foundation 2020A1515111150Guangdong Provincial Second Hospital of Traditional Chinese Medicine Scientific research innovation Foundation SEZYY2023A12Guang Zhou Basic and Applied Basic Research Foundation SL2023A04J02259Medical Scientific Research Foundation of Guangdong Province B2020207Xiamen Medical and Health Guidance Project 3502Z20244ZD1178
6 · The paper itself

Abstract

backgroundSkin cutaneous melanoma (SKCM) is a life-threatening malignancy, and pyroptosis-mediated inflammatory response is associated with SKCM progression. We aimed to uncover the underlying pathogenesis of SKCM based on pyroptosis features.

methodThe single-cell and bulk RNA-seq data and clinical information of SKCM patients were downloaded from the TCGA and GEO databases, and the REACTOME_ PYROPTOSIS.v2024.1.Hs.gmt from the MSigDB database was used for Gene Set Enrichment Analysis (GSEA). Differentially expressed gene (DEG) analysis was performed utilizing the "limma" R package, and the "GSVA" R package was used for the analysis of pyroptosis pathway activation. In addition, scRNA-seq analysis and cell communication analysis were carried out by employing the "Seurat" R package and "CellChat" R package, respectively. Gene expression was measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR), while cell counting kit-8 (CCK-8), wound healing, and Transwell assays were carried out to assess cell proliferation, migration, and invasion, respectively.

resultsDEGs analysis detected no significant pyroptosis-related DEGs. Analysis of the expression of two representative pyroptosis genes (GZMA and GSDMB) revealed that GZMA was significantly upregulated in the SKCM tissues, but the expression of GSDMB was downregulated. The pyroptosis pathway was not activated in the tumor group. In addition, we observed that high expression of GZMA and GSDMB was closely associated with a favorable outcome in SKCM. The two genes were downregulated in SKCM cells, while the overexpression of GZMA significantly impaired the proliferation, migration, and invasion ability of SKCM cells. Nine main cell subpopulations were identified, and GZMA was specifically overexpressed in CD8+ T cells. Gene function analysis revealed that specific genes of CD8+ T cells were enriched in cell death-related and inflammation activation pathways. Cell communication demonstrated that CD8+ T cells interacted with melanocytes through the CD99-CD99 and HLA-C-KIR2DL3 ligand-receptor pairs.

conclusionBased on the pyroptosis features in SKCM, this study found that blocking GZMA protein in CD8+ T cells within melanocytes may be the potential underlying pathogenesis for tumor immune escape in cancer.

Indexed as

CD8-Positive T-LymphocytesGranzymesImmune EvasionMelanomaPyroptosisSkin NeoplasmsCell ProliferationCutaneous Malignant MelanomaHumansGranzymesCD8+ T cellsDifferential expression analysisPrognostic analysisPyroptosis featuresSingle-cell analysisSkin cutaneous melanoma

Identifiers

PMID40755114

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