Wang Peng, Han Liying, Yu Moxin, Cao Zhengyu, Li Xiaoning, Shao Yunxia, Zhu Guoping
Anhui Provincial Key Laboratory of Molecular Enzymology and Mechanism of Major Diseases, Key Laboratory of Biomedicine in Gene Diseases, Health of Anhui Higher Education Institutes, Anhui Normal University, Wuhu, China.
Department of Clinical Laboratory, Yijishan Hospital of Wannan Medical College, Wuhu, China.
Front Mol Biosci. 2021 Apr 16;8:648752. doi: 10.3389/fmolb.2021.648752. eCollection 2021.
Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) is a type I transmembrane protein that functions as an endoplasmic reticulum (ER) stress sensor to regulate global protein synthesis. Recent research studies suggest that PERK, as an important receptor protein of unfolded protein response, is involved in the pathogenesis of many cancers. This study aimed to investigate PERK expression and its relationship with prognosis in pan-cancer and attempted to explore the relevant mechanism of PERK involved in the regulation of cancer pathogenesis. The Oncomine and TIMER databases were used to analyze the expression of PERK between pan-cancer samples and normal samples. Survival analysis was performed using the PrognoScan, Kaplan-Meier (K-M) plotter, and UALCAN databases. Gene set enrichment analysis (GSEA) was used to perform the functional enrichment analysis of the PERK gene in breast invasive carcinoma (BRCA), head and neck squamous cell carcinoma (HNSC), and thyroid carcinoma (THCA). The TIMER database was used to investigate the correlation between PERK expression and tumor-infiltrating immune cells and analyze the relationship of PERK with marker genes of immune cells which were downloaded from the CellMarker database in BRCA, HNSC, and THCA. PERK was differentially expressed in various cancers, such as breast cancer, liver cancer, lung cancer, gastric carcinoma, lymphoma, thyroid cancer, leukemia, and head and neck squamous cell carcinomas. The high expression of PERK was associated with a poor prognosis in KIRP, LGG, BRCA, and THCA and with a favorable prognosis in HNSC. The results of GSEA indicated that PERK was mainly enriched in immune-related signaling pathways in BRCA, HNSC, and THCA. Moreover, PERK expression was significant positively correlated with infiltrating levels of macrophages and dendritic cells and was strongly associated with a variety of immune markers, especially macrophage mannose receptor 1 (MRC1, also called CD206) and T-helper cells (Th). The high expression of PERK could promote the infiltration of multiple immune cells in the tumor microenvironment and could deteriorate the outcomes of patients with breast and thyroid cancers, suggesting that PERK as well as tumor-infiltrating immune cells could be taken as potential biomarkers of prognosis.
蛋白激酶R（PKR）样内质网激酶（PERK）是一种I型跨膜蛋白，作为内质网（ER）应激传感器发挥作用，以调节整体蛋白质合成。最近的研究表明，PERK作为未折叠蛋白反应的重要受体蛋白，参与了多种癌症的发病机制。本研究旨在调查泛癌中PERK的表达及其与预后的关系，并试图探索PERK参与癌症发病机制调控的相关机制。使用Oncomine和TIMER数据库分析泛癌样本与正常样本之间PERK的表达。使用PrognoScan、Kaplan-Meier（K-M）绘图仪和UALCAN数据库进行生存分析。基因集富集分析（GSEA）用于对乳腺浸润性癌（BRCA）、头颈部鳞状细胞癌（HNSC）和甲状腺癌（THCA）中PERK基因进行功能富集分析。使用TIMER数据库研究PERK表达与肿瘤浸润免疫细胞之间的相关性，并分析PERK与从BRCA、HNSC和THCA的CellMarker数据库下载的免疫细胞标记基因的关系。PERK在各种癌症中差异表达，如乳腺癌、肝癌、肺癌、胃癌、淋巴瘤、甲状腺癌、白血病和头颈部鳞状细胞癌。PERK的高表达与肾嫌色细胞癌（KIRP）、低级别胶质瘤（LGG）、BRCA和THCA的预后不良相关，而与HNSC的预后良好相关。GSEA结果表明，PERK主要在BRCA、HNSC和THCA的免疫相关信号通路中富集。此外，PERK表达与巨噬细胞和树突状细胞的浸润水平显著正相关，并且与多种免疫标记物密切相关，尤其是巨噬细胞甘露糖受体1（MRC1，也称为CD206）和辅助性T细胞（Th）。PERK的高表达可促进肿瘤微环境中多种免疫细胞的浸润，并可能使乳腺癌和甲状腺癌患者的预后恶化，这表明PERK以及肿瘤浸润免疫细胞可作为潜在的预后生物标志物。
