综合分析显示，GRP94与乳腺癌的不良预后相关。

Comprehensive analysis reveals GRP94 is associated with worse prognosis of breast cancer.

作者信息

Wang Ting, Yang Lei, Li Chunxiao, Wang Jinsong, Zhang Jingyao, Zhou Yantong, Sun Fangzhou, Wang Haijuan, Ma Fei, Qian Haili

机构信息

State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Department of Imaging Diagnostic, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

Transl Cancer Res. 2021 Jan;10(1):298-309. doi: 10.21037/tcr-20-1853.

DOI:10.21037/tcr-20-1853

PMID:35116261

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8798085/

Abstract

BACKGROUND

Breast cancer (BC) is the most common cancer diagnosed in women around the world. Glucose-related protein 94 (GRP94) is a molecular chaperone on the endoplasmic reticulum (ER) that is associated with many malignancies, although its role in breast carcinogenesis has remained unclear. This study aimed to investigate the expression of GRP94 in BC and its relationship with BC clinicopathological features and prognosis based on a comprehensive analysis.

METHODS

The mutation and expression patterns of GRP94 in multiple cancers were elucidated from TCGA data. A GRP94 IS (immune score) was generated from breast tumors in Chinese women by multiplying the staining intensity and the percentage of positive cells. The relationship between GRP94 expression and clinicopathological parameters in TMA samples was identified by Spearman correlation analysis. We established a GRP94 co-expression interaction network from two databases (TCGA and STRING). Overall survival (OS) and relapse-free survival (RFS) were determined via the KM-plotter analysis platform.

RESULTS

GRP94 is mutated in most cancer types, and the average mutation frequency is 1.1%. GRP94 expression in BC was in the middle of the expression levels of the analyzed cancer types. The protein level of GRP94 was significantly higher in BC tissues than in normal breast tissues. A high level of GRP94 was positively associated with the levels of PR and AR and negatively associated with the level of EGFR but was not associated with age, pathological types, pathological grades, clinical stages or the levels of ER, HER2, P53, Ki67, or CK5/6. High expression of GRP94 predicted decreased OS and RFS in BC. The cluster analysis of the gene coexpression network showed six dominant biological events, including ribosome biogenesis, amino acid activation, ER stress, protein folding and protein localization to the nucleus, cell cycle processes and ubiquitin-protein ligase activity involved in the mitotic cell cycle.

CONCLUSIONS

The study suggests that GRP94 could be a potential prognostic factor in BC.

摘要

背景

乳腺癌（BC）是全球女性中最常被诊断出的癌症。葡萄糖相关蛋白94（GRP94）是内质网（ER）上的一种分子伴侣，与许多恶性肿瘤相关，但其在乳腺癌发生中的作用仍不清楚。本研究旨在通过综合分析来探究GRP94在乳腺癌中的表达及其与乳腺癌临床病理特征和预后的关系。

方法

从TCGA数据中阐明GRP94在多种癌症中的突变和表达模式。通过将染色强度与阳性细胞百分比相乘，得出中国女性乳腺肿瘤的GRP94免疫评分（IS）。通过Spearman相关分析确定TMA样本中GRP94表达与临床病理参数之间的关系。我们从两个数据库（TCGA和STRING）建立了GRP94共表达相互作用网络。通过KM-plotter分析平台确定总生存期（OS）和无复发生存期（RFS）。

结果

GRP94在大多数癌症类型中发生突变，平均突变频率为1.1%。乳腺癌中GRP94的表达处于所分析癌症类型表达水平的中间。乳腺癌组织中GRP94的蛋白水平明显高于正常乳腺组织。GRP94高水平与PR和AR水平呈正相关，与EGFR水平呈负相关，但与年龄、病理类型、病理分级、临床分期或ER、HER2、P53、Ki67或CK5/6水平无关。GRP94高表达预示着乳腺癌患者的OS和RFS降低。基因共表达网络的聚类分析显示了六个主要生物学事件，包括核糖体生物合成、氨基酸激活、内质网应激、蛋白质折叠和蛋白质向细胞核的定位、细胞周期过程以及有丝分裂细胞周期中涉及的泛素-蛋白连接酶活性。