Development and validation of an endoplasmic reticulum stress-related molecular prognostic model for breast cancer.
Development and validation of an endoplasmic reticulum stress-related molecular prognostic model for breast cancer.
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DOI：
10.3389/fonc.2023.1178595
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发表时间：
2023
影响因子：
4.7
通讯作者：
Ling, Rui
中科院分区：
文献类型：
--
作者：
Fan, Pengyu;Wang, Jiajia;Li, Ruolei;Chang, Kexin;Liu, Liuyin;Wang, Yaping;Wang, Zhe;Zhang, Bo;Ji, Cheng;Zhang, Jian;Chen, Suning;Ling, Rui
关键词：
乳腺癌是最常见的癌症，也是妇女癌症相关死亡的主要原因。内质网应激（ERS）在几种恶性肿瘤的发病机制中起着至关重要的作用。然而，雌激素受体相关基因在乳腺癌中的预后价值尚未得到彻底研究。我们下载并分析了乳腺浸润性癌样本的表达谱数据，并在癌症基因组乳腺浸润性癌（TCGA-BRCA）中确定了23个在正常乳腺组织和原发性乳腺肿瘤组织之间差异表达的ERS相关基因。我们使用外部测试数据集构建并验证了风险模型。我们使用癌症药物敏感性基因组学（GDSC）数据库评估了高分组和低分组之间对常见抗肿瘤药物的敏感性差异，使用肿瘤免疫功能障碍和排除（TIDE）算法评估了高分组和低分组患者对免疫治疗的敏感性，并使用使用表达数据估计恶性肿瘤组织中的基质和免疫细胞（ESTIMATE）算法评估肿瘤微环境（TME）中的免疫和基质细胞浸润。我们还分析了表达的独立因素的预后模型，使用蛋白质印迹分析相关的乳腺癌。多因素考克斯分析发现FBXO 6、PMAIP 1、ERP 27和CHAC 1是乳腺癌患者的独立预后因素。我们模型中的风险评分定义为内质网评分（ER评分）。ER评分对乳腺癌患者的总生存率有较高的预测能力。高ER评分组与低ER评分组相比，预后更差，药物敏感性更低，免疫治疗反应和免疫浸润更低。ERScore的结果与Western-blot结果一致。我们首次构建并验证了乳腺癌内质网应激相关分子预后模型，该模型具有可靠的预测特性和良好的灵敏度，作为乳腺癌预后预测模型的重要补充。
Breast cancer is the most frequently diagnosed cancer and a leading cause of cancer-related death in women. Endoplasmic reticulum stress (ERS) plays a crucial role in the pathogenesis of several malignancies. However, the prognostic value of ERS-related genes in breast cancer has not been thoroughly investigated. We downloaded and analyzed expression profiling data for breast invasive carcinoma samples in The Cancer Genome Atlas-Breast Invasive Carcinoma (TCGA-BRCA) and identified 23 ERS-related genes differentially expressed between the normal breast tissue and primary breast tumor tissues. We constructed and validated risk models using external test datasets. We assessed the differences in sensitivity to common antitumor drugs between high- and low-scoring groups using the Genomics of Drug Sensitivity in Cancer (GDSC) database, evaluated the sensitivity of patients in high- and low-scoring groups to immunotherapy using the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm, and assessed immune and stromal cell infiltration in the tumor microenvironment (TME) using the Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) algorithm. We also analyzed the expression of independent factors in the prognostic model using the Western-blot analysis for correlation in relation to breast cancer. Using multivariate Cox analysis, FBXO6, PMAIP1, ERP27, and CHAC1 were identified as independent prognostic factors in patients with breast cancer. The risk score in our model was defined as the endoplasmic reticulum score (ERScore). ERScore had high predictive power for overall survival in patients with breast cancer. The high-ERScore group exhibited a worse prognosis, lower drug sensitivity, and lower immunotherapy response and immune infiltration than did the low-ERScore group. Conclusions based on ERScore were consistent with Western-blot results. We constructed and validated for the first time an endoplasmic reticulum stress-related molecular prognostic model for breast cancer with reliable predictive properties and good sensitivity, as an important addition to the prognostic prediction model for breast cancer.
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影响因子：
4.9
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14.9
作者：
Colaprico A;Silva TC;Olsen C;Garofano L;Cava C;Garolini D;Sabedot TS;Malta TM;Pagnotta SM;Castiglioni I;Ceccarelli M;Bontempi G;Noushmehr H
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Noushmehr H
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Jackowski, Suzanne
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Chen, Xi;Iliopoulos, Dimitrios;Zhang, Qing;Tang, Qianzi;Greenblatt, Matthew B.;Hatziapostolou, Maria;Lim, Elgene;Tam, Wai Leong;Ni, Min;Chen, Yiwen;Mai, Junhua;Shen, Haifa;Hu, Dorothy Z.;Adoro, Stanley;Hu, Bella;Song, Minkyung;Tan, Chen;Landis, Melissa D.;Ferrari, Mauro;Shin, Sandra J.;Brown, Myles;Chang, Jenny C.;Liu, X. Shirley;Glimcher, Laurie H.
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Glimcher, Laurie H.
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254.7
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Siegel, Rebecca L.;Miller, Kimberly D.;Jemal, Ahmedin
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Jemal, Ahmedin