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全凋亡相关基因在皮肤黑色素瘤中的作用及预后价值

The role and prognostic value of PANoptosis-related genes in skin cutaneous melanoma.

作者信息

Feng Huijing, Jia Linzi, Ma Yanan, Liu Pengmin, Yang Xiaoling, Hu Lina, Xu Kai, Yang Fan, Zhang Dongfeng, Li Jian, Mei Qi, Han Fei

机构信息

Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.

Department of General Medicine, Shanxi Province Cancer Hospital, Taiyuan, Shanxi, China.

出版信息

Front Immunol. 2025 Jun 6;16:1605977. doi: 10.3389/fimmu.2025.1605977. eCollection 2025.

Abstract

INTRODUCTION

Skin cutaneous melanoma (SKCM), a malignant tumor, has PANoptosis implicated in its progression and metastasis. However, the exact mechanisms remain unclear. This study aims to develop a prognostic model for SKCM based on PANoptosis.

METHODS

SKCM - related datasets were retrieved from public databases. Differentially expressed PANoptosis - related genes (DEPRGs) were determined by intersecting differentially expressed genes from differential expression analysis and key module genes from weighted gene co - expression network analysis (WGCNA). Prognostic genes for SKCM were derived using Cox analysis and machine learning algorithms, leading to the construction and validation of a prognostic model. Independent prognostic factors were identified, and a nomogram was developed. Enrichment analysis and immune infiltration analysis were performed for the two risk groups. A competitive endogenous RNA (ceRNA) network was constructed, and potential therapeutic drugs were predicted. Bioinformatics findings were validated experimentally using reverse transcription quantitative PCR (RT - qPCR).

RESULTS

CD8A, ADAMDEC1, CD69, CRIP1, LSP1, BCL11B, and CCR7 were identified as prognostic genes. The risk model and nomogram showed excellent predictive abilities for SKCM patients. Genes in both high - and low - risk groups were linked to cytokine - regulated immune responses, with nine differential immune cells identified between the groups. The ceRNA network revealed that prognostic genes were regulated by several miRNAs (such as hsa-miR-330-5p) and lncRNAs (such as AL355075.4). MPPG and DT - 1687, associated with LSP1, may offer promising treatment options. RT - qPCR validation confirmed significant expression differences of CD8A, ADAMDEC1, CD69, CRIP1, and BCL11B between SKCM and control samples.

DISCUSSION

This study presents a robust prognostic model for SKCM based on PANoptosis - related genes, providing a theoretical foundation for SKCM treatment.

摘要

引言

皮肤黑色素瘤(SKCM)是一种恶性肿瘤,细胞焦亡参与其进展和转移。然而,确切机制尚不清楚。本研究旨在基于细胞焦亡建立SKCM的预后模型。

方法

从公共数据库中检索SKCM相关数据集。通过将差异表达分析中的差异表达基因与加权基因共表达网络分析(WGCNA)中的关键模块基因相交,确定差异表达的细胞焦亡相关基因(DEPRGs)。使用Cox分析和机器学习算法得出SKCM的预后基因,从而构建并验证预后模型。识别独立预后因素并绘制列线图。对两个风险组进行富集分析和免疫浸润分析。构建竞争性内源性RNA(ceRNA)网络并预测潜在治疗药物。使用逆转录定量PCR(RT-qPCR)对生物信息学结果进行实验验证。

结果

CD8A、ADAMDEC1、CD69、CRIP1、LSP1、BCL11B和CCR7被确定为预后基因。风险模型和列线图对SKCM患者显示出优异的预测能力。高风险组和低风险组中的基因均与细胞因子调节的免疫反应相关,两组之间鉴定出9种差异免疫细胞。ceRNA网络显示预后基因受几种miRNA(如hsa-miR-330-5p)和lncRNA(如AL355075.4)调控。与LSP1相关的MPPG和DT-1687可能提供有前景的治疗选择。RT-qPCR验证证实SKCM与对照样本之间CD8A、ADAMDEC1、CD69、CRIP1和BCL11B存在显著表达差异。

讨论

本研究基于细胞焦亡相关基因提出了一个强大的SKCM预后模型,为SKCM治疗提供了理论基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3558/12179157/fe85f600d363/fimmu-16-1605977-g001.jpg

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