Fan Pengyu, Wang Jiajia, Li Ruolei, Chang Kexin, Liu Liuyin, Wang Yaping, Wang Zhe, Zhang Bo, Ji Cheng, Zhang Jian, Chen Suning, Ling Rui
Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, China.
Front Oncol. 2023 May 29;13:1178595. doi: 10.3389/fonc.2023.1178595. eCollection 2023.
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, , , , and 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.
乳腺癌是女性中最常被诊断出的癌症，也是癌症相关死亡的主要原因。内质网应激（ERS）在多种恶性肿瘤的发病机制中起关键作用。然而，ERS相关基因在乳腺癌中的预后价值尚未得到充分研究。
我们下载并分析了癌症基因组图谱-乳腺浸润性癌（TCGA-BRCA）中乳腺浸润性癌样本的表达谱数据，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）数据库评估了高分和低分群体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）算法评估了高分和低分群体患者对免疫治疗的敏感性，并使用基于表达数据的恶性肿瘤组织中基质和免疫细胞估计（ESTIMATE）算法评估了肿瘤微环境（TME）中的免疫和基质细胞浸润。我们还使用蛋白质免疫印迹分析来分析预后模型中独立因素的表达与乳腺癌的相关性。
通过多变量Cox分析，确定 、 、 和 为乳腺癌患者的独立预后因素。我们模型中的风险评分被定义为内质网评分（ERScore）。ERScore对乳腺癌患者的总生存期具有较高的预测能力。高ERScore组的预后较差，药物敏感性较低，免疫治疗反应和免疫浸润低于低ERScore组。基于ERScore得出的结论与蛋白质免疫印迹结果一致。
我们首次构建并验证了一种具有可靠预测特性和良好敏感性的内质网应激相关的乳腺癌分子预后模型，作为乳腺癌预后预测模型的重要补充。
