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细胞焦亡相关基因在预测乳腺癌生存及免疫前景中的作用

The Role of PANoptosis-Related Genes in Predicting Breast Cancer Survival and Immune Prospect.

作者信息

Zhang Yuxi, Liu Zheming, Zhang Yixuan, Zhang Xue, Yao Yi, Zhang Chi

机构信息

Department of Radiation Oncology, The First Affiliated Hospital With Nanjing Medical University, Nanjing, China.

Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China.

出版信息

Biomed Res Int. 2025 May 28;2025:3423698. doi: 10.1155/bmri/3423698. eCollection 2025.

Abstract

The function of PANoptosis in breast cancer (BC) remains indistinct. We constructed a nomogram model to predict the prognosis of BC to identify high-risk patients and help them receive more accurate treatment. We used Cox regression and least absolute shrinkage and selection operator (LASSO) algorithm to select PANoptosis-related genes (PRGs) and calculated the PANoptosis-related score (PRS) by LASSO coefficient. Through functional enrichment, somatic mutation, and tumor microenvironment (TME) analysis, we completed the identification of PANoptosis-related immune cells and difference analysis of drug sensitivity and then verified key genes by performing survival analysis. Patients were divided into low- and high-risk cohorts depending on PRS, and the negative association between risk scores and overall survival was disclosed. Analysis showed that differentially expressed genes in the two risk cohorts were mainly concentrated among pathways related to the immune system. Moreover, we detected distinguished differences in immune checkpoints, tumor mutation load, and TME in the two cohorts. Furthermore, KLHDC7B, GNG8, IGKV1OR2-108, and IGHD were identified as key genes. We also found that hub genes were highly expressed in tumor tissues, while B cells, CD4+, and CD8+ T cells pretended to be positive among the hub gene-negative cohort. Prognosis analysis showed that pivotal genes had adverse effects on survival over time. We built a precise prediction model based on risk scores and proved the significance of PRGs in BC TME and medicine sensitivity regulation, providing key perception for subsequent molecular mechanism studies and contributing to more personalized treatment decisions in clinical practice.

摘要

焦亡在乳腺癌(BC)中的作用仍不明确。我们构建了一个列线图模型来预测BC的预后,以识别高危患者并帮助他们接受更准确的治疗。我们使用Cox回归和最小绝对收缩选择算子(LASSO)算法来选择焦亡相关基因(PRG),并通过LASSO系数计算焦亡相关评分(PRS)。通过功能富集、体细胞突变和肿瘤微环境(TME)分析,我们完成了焦亡相关免疫细胞的鉴定以及药物敏感性差异分析,然后通过生存分析验证关键基因。根据PRS将患者分为低风险和高风险队列,并揭示了风险评分与总生存期之间的负相关关系。分析表明,两个风险队列中差异表达的基因主要集中在与免疫系统相关的通路中。此外,我们在两个队列中检测到免疫检查点、肿瘤突变负荷和TME存在显著差异。此外,KLHDC7B、GNG8、IGKV1OR2 - 108和IGHD被确定为关键基因。我们还发现,枢纽基因在肿瘤组织中高表达,而在枢纽基因阴性队列中,B细胞、CD4 + 和CD8 + T细胞呈阳性。预后分析表明,关键基因对长期生存有不利影响。我们基于风险评分建立了一个精确的预测模型,证明了PRG在BC TME和药物敏感性调节中的重要性,为后续分子机制研究提供了关键认识,并有助于临床实践中做出更个性化的治疗决策。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a503/12136870/003dc75bc8a0/BMRI2025-3423698.001.jpg

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