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一种基于乳腺癌焦亡相关簇的新型预后预测模型。

A Novel Prognostic Prediction Model Based on Pyroptosis-Related Clusters for Breast Cancer.

作者信息

Tian Baoxing, Yin Kai, Qiu Xia, Sun Haidong, Zhao Ji, Du Yibao, Gu Yifan, Wang Xingyun, Wang Jie

机构信息

Department of Breast Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, No. 1111, Xianxia Road, Shanghai 200336, China.

Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, No. 1111, Xianxia Road, Shanghai 200336, China.

出版信息

J Pers Med. 2022 Dec 28;13(1):69. doi: 10.3390/jpm13010069.

Abstract

Breast cancer (BC) is the most common cancer affecting women and the leading cause of cancer-related deaths worldwide. Compelling evidence indicates that pyroptosis is inextricably involved in the development of cancer and may activate tumor-specific immunity and/or enhance the effectiveness of existing therapies. We constructed a novel prognostic prediction model for BC, based on pyroptosis-related clusters, according to RNA-seq and clinical data downloaded from TCGA. The proportions of tumor-infiltrating immune cells differed significantly in the two pyroptosis clusters, which were determined according to 38 pyroptosis-related genes, and the immune-related pathways were activated according to GO and KEGG enrichment analysis. A 56-gene signature, constructed using univariate and multivariate Cox regression, was significantly associated with progression-free interval (PFI), disease-specific survival (DSS), and overall survival (OS) of patients with BC. Cox analysis revealed that the signature was significantly associated with the PFI and DSS of patients with BC. The signature could efficiently distinguish high- and low-risk patients and exhibited high sensitivity and specificity when predicting the prognosis of patients using KM and ROC analysis. Combined with clinical risk, patients in both the gene and clinical low-risk subgroup who received adjuvant chemotherapy had a significantly lower incidence of the clinical event than those who did not. This study presents a novel 56-gene prognostic signature significantly associated with PFI, DSS, and OS in patients with BC, which, combined with the TNM stage, might be a potential therapeutic strategy for individualized clinical decision-making.

摘要

乳腺癌(BC)是影响女性的最常见癌症,也是全球癌症相关死亡的主要原因。有力证据表明,细胞焦亡与癌症发展密切相关,可能激活肿瘤特异性免疫和/或增强现有疗法的有效性。我们根据从TCGA下载的RNA测序和临床数据,构建了一种基于细胞焦亡相关聚类的新型BC预后预测模型。根据38个细胞焦亡相关基因确定的两个细胞焦亡聚类中,肿瘤浸润免疫细胞的比例有显著差异,并且根据GO和KEGG富集分析,免疫相关途径被激活。使用单变量和多变量Cox回归构建的56基因特征与BC患者的无进展生存期(PFI)、疾病特异性生存期(DSS)和总生存期(OS)显著相关。Cox分析显示,该特征与BC患者的PFI和DSS显著相关。该特征可以有效区分高风险和低风险患者,并且在使用KM和ROC分析预测患者预后时表现出高敏感性和特异性。结合临床风险,基因和临床低风险亚组中接受辅助化疗的患者临床事件发生率显著低于未接受辅助化疗的患者。本研究提出了一种与BC患者的PFI、DSS和OS显著相关的新型56基因预后特征,结合TNM分期,可能是个性化临床决策的潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ffd/9865451/e4cad4e203df/jpm-13-00069-g001a.jpg

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