Zhu Lizhe, Wu Wei, Jiang Siyuan, Yu Shibo, Yan Yu, Wang Ke, He Jianjun, Ren Yu, Wang Bin
Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Front Oncol. 2020 Nov 10;10:569887. doi: 10.3389/fonc.2020.569887. eCollection 2020.
The PINK1 gene encodes a serine/threonine protein kinase that localizes to mitochondria and has usually been considered to protect cells from stress-induced mitochondrial dysfunction. PINK1 mutations have been observed to lead to autosomal recessive Parkinson's disease. However, the immunological and prognostic roles of PINK1 across cancers remain unclear.
In the current study, we used multiple databases, including Oncomine, PrognoScan, Kaplan-Meier Plotter, GEPIA, TIMER, and cBioportal, to investigate the PINK1 expression distribution and its immunological and prognostic role across cancers.
Bioinformatics data revealed that the mRNA expression of PINK1 was downregulated in most tumors. Although there was a significant prognostic value of PINK1 expression across cancers, PINK1 played a protective or detrimental role in different kinds of cancers. Liver hepatocellular carcinoma and lung squamous cell carcinoma were selected as representative cancer types for further exploration. We found that PINK1 always played a protective role in liver hepatocellular carcinoma patients in the stratified prognostic analyses of clinicopathological characteristics. There were contradictory results between liver hepatocellular carcinoma and lung squamous cell carcinoma in the correlations of PINK1 expression with immune infiltration, including infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. Furthermore, specific markers of B cells and CD8+ T cells also exhibited different PINK1-related immune infiltration patterns. In addition, there was a significant association between PINK1 copy number variations and immune infiltrates across cancers.
The mitophagy-related protein PINK1 can work as a biomarker for prognosis and the immune response across cancers.
PINK1基因编码一种丝氨酸/苏氨酸蛋白激酶,定位于线粒体,通常被认为可保护细胞免受应激诱导的线粒体功能障碍。已观察到PINK1突变会导致常染色体隐性帕金森病。然而,PINK1在各种癌症中的免疫和预后作用仍不清楚。
在本研究中,我们使用了多个数据库,包括Oncomine、PrognoScan、Kaplan-Meier Plotter、GEPIA、TIMER和cBioportal,以研究PINK1的表达分布及其在各种癌症中的免疫和预后作用。
生物信息学数据显示,PINK1的mRNA表达在大多数肿瘤中下调。尽管PINK1表达在各种癌症中具有显著的预后价值,但PINK1在不同类型的癌症中发挥着保护或有害作用。选择肝细胞癌和肺鳞状细胞癌作为代表性癌症类型进行进一步探索。我们发现在临床病理特征的分层预后分析中,PINK1在肝细胞癌患者中始终发挥保护作用。在PINK1表达与免疫浸润(包括B细胞、CD8+T细胞、CD4+T细胞、巨噬细胞、中性粒细胞和树突状细胞的浸润)的相关性方面,肝细胞癌和肺鳞状细胞癌之间存在矛盾的结果。此外,B细胞和CD8+T细胞的特异性标志物也表现出不同的PINK1相关免疫浸润模式。此外,PINK1拷贝数变异与各种癌症中的免疫浸润之间存在显著关联。
与线粒体自噬相关的蛋白PINK1可作为各种癌症预后和免疫反应的生物标志物。