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建立细胞坏死性凋亡指数以预测三阴性乳腺癌患者的预后和药物敏感性

Establishment of a Cell Necroptosis Index to Predict Prognosis and Drug Sensitivity for Patients With Triple-Negative Breast Cancer.

作者信息

Xie Jindong, Tian Wenwen, Tang Yuhui, Zou Yutian, Zheng Shaoquan, Wu Linyu, Zeng Yan, Wu Song, Xie Xinhua, Xie Xiaoming

机构信息

Department of Breast Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

出版信息

Front Mol Biosci. 2022 May 5;9:834593. doi: 10.3389/fmolb.2022.834593. eCollection 2022.

Abstract

Necroptosis has been an alternatively identified mechanism of programmed cancer cell death, which plays a significant role in cancer. However, research about necroptosis-related long noncoding RNAs (lncRNAs) in cancer are still few. Moreover, the potentially prognostic value of necroptosis-related lncRNAs and their correlation with the immune microenvironment remains unclear. The present study aimed to explore the potential prognostic value of necroptosis-related lncRNAs and their relationship to immune microenvironment in triple-negative breast cancer (TNBC). The RNA expression matrix of patients with TNBC was obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Finally, 107 patients of GSE58812, 159 patients of TCGA, and 143 patients of GSE96058 were included. Necroptosis-related lncRNAs were screened by Cox regression and Pearson correlation analysis with necroptosis-related genes. By LASSO regression analysis, nine necroptosis-related lncRNAs were employed, and a cell necroptosis index (CNI) was established; then, we evaluated its prognostic value, clinical significance, pathways, immune infiltration, and chemotherapeutics efficacy. Based on the CNI value, the TNBC patients were divided into high- and low-CNI groups, and the patients with high CNI had worse prognosis, more lymph node metastasis, and larger tumor ( < 0.05). The receiver operating characteristic (ROC) analysis showed that the signature performed well. The result of the infiltration proportion of different immune cell infiltration further explained that TNBC patients with high CNI had low immunogenicity, leading to poor therapeutic outcomes. Moreover, we found significant differences of the IC50 values of various chemotherapeutic drugs in the two CNI groups, which might provide a reference to make a personalized chemotherapy for them. The novel prognostic marker CNI could not only precisely predict the survival probability of patients with TNBC but also demonstrate a potential role in antitumor immunity and drug sensitivity.

摘要

坏死性凋亡是一种已被确定的程序性癌细胞死亡机制,在癌症中发挥着重要作用。然而,关于癌症中与坏死性凋亡相关的长链非编码RNA(lncRNA)的研究仍然很少。此外,与坏死性凋亡相关的lncRNA的潜在预后价值及其与免疫微环境的相关性仍不清楚。本研究旨在探讨与坏死性凋亡相关的lncRNA在三阴性乳腺癌(TNBC)中的潜在预后价值及其与免疫微环境的关系。TNBC患者的RNA表达矩阵来自癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)。最后,纳入了GSE58812的107例患者、TCGA的159例患者和GSE96058的143例患者。通过Cox回归和与坏死性凋亡相关基因的Pearson相关性分析筛选出与坏死性凋亡相关的lncRNA。通过LASSO回归分析,使用了9种与坏死性凋亡相关的lncRNA,并建立了细胞坏死性凋亡指数(CNI);然后,我们评估了其预后价值、临床意义、通路、免疫浸润和化疗疗效。根据CNI值,将TNBC患者分为高CNI组和低CNI组,高CNI患者的预后更差,淋巴结转移更多,肿瘤更大(P<0.05)。受试者工作特征(ROC)分析表明该特征表现良好。不同免疫细胞浸润比例的结果进一步说明,高CNI的TNBC患者免疫原性低,导致治疗效果差。此外,我们发现两种CNI组中各种化疗药物的IC50值存在显著差异,这可能为为他们制定个性化化疗提供参考。新的预后标志物CNI不仅可以精确预测TNBC患者的生存概率,还可以在抗肿瘤免疫和药物敏感性方面发挥潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48ec/9117653/929e3e831e72/fmolb-09-834593-g001.jpg

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