Li Nan, Zhao Jing, Ma Yibing, Roy Bhaskar, Liu Ren, Kristiansen Karsten, Gao Qiang
Laboratory of Molecular Medicine, Medical College, Eastern Liaoning University, Dandong, Liaoning 118003, P.R. China.
BGI Genomics, BGI-Shenzhen, Yantian, Shenzhen, Guangdong 518083, P.R. China.
Oncol Lett. 2018 Sep;16(3):3992-4000. doi: 10.3892/ol.2018.9113. Epub 2018 Jul 10.
Lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) are the two major subtypes of lung cancer. To explore mitochondrial respiratory gene expression profiles in LUSC and LUAD, RNA sequencing data from The Cancer Genome Atlas was used for comprehensive analyses to establish the molecular characteristics of LUSC and LUAD. To elucidate expression profiles, subtypes were defined using unsupervised clustering of mitochondrial gene expression data. Differences in nuclear gene expression levels, signaling pathways and tumor microenvironments between subtypes were investigated. The analysis revealed that mitochondrial respiratory genes were generally expressed at lower levels in tumor tissues compared with matched control tissues. The expression of mitochondrially encoded NADH dehydrogenase 5 or 6 was associated with tumor progression in LUAD and LUSC. Patients were clustered into three subgroups based on the expression profile of 13 mitochondrial protein-encoding genes, and patients in Cluster 3 exhibited poor survival rates compared with patients from Cluster 1. Furthermore, this association was also observed in another independent data set. Further analyses of the expression of nuclear-encoded genes in the three clusters revealed the enrichment of several cancer-associated signaling pathways in Cluster 3, particularly the apoptotic signaling pathway, suggesting a potential association between the decreased expression of mitochondrial DNA genes and increased tumor aggressiveness. Furthermore, the analyses of immune cell compositions in the tumor microenvironment detected a significant increase in the proportion of CD4 T cells and a decrease in the proportion of macrophages in LUAD compared with LUSC (P=0.0000104 and P=0.0000105, respectively). In conclusion, the present study revealed an association between the expression patterns of mitochondrial-encoded genes and lung cancer, which may contribute to novel therapeutic strategies for patients with LUSC and LUAD.
肺鳞状细胞癌（LUSC）和肺腺癌（LUAD）是肺癌的两种主要亚型。为了探究LUSC和LUAD中线粒体呼吸基因的表达谱，利用来自癌症基因组图谱的RNA测序数据进行综合分析，以确定LUSC和LUAD的分子特征。为了阐明表达谱，使用线粒体基因表达数据的无监督聚类来定义亚型。研究了各亚型之间核基因表达水平、信号通路和肿瘤微环境的差异。分析显示，与匹配的对照组织相比，肿瘤组织中线粒体呼吸基因的表达水平通常较低。线粒体编码的NADH脱氢酶5或6的表达与LUAD和LUSC中的肿瘤进展相关。根据13个线粒体蛋白编码基因的表达谱将患者分为三个亚组，与第1组患者相比，第3组患者的生存率较差。此外，在另一个独立数据集中也观察到了这种关联。对三个亚组中核编码基因表达的进一步分析揭示了第3组中几种癌症相关信号通路的富集，特别是凋亡信号通路，这表明线粒体DNA基因表达降低与肿瘤侵袭性增加之间可能存在关联。此外，对肿瘤微环境中免疫细胞组成的分析发现，与LUSC相比，LUAD中CD4 T细胞比例显著增加，巨噬细胞比例降低（分别为P = 0.0000104和P = 0.0000105）。总之，本研究揭示了线粒体编码基因的表达模式与肺癌之间的关联，这可能有助于为LUSC和LUAD患者制定新的治疗策略。
