Li Shicheng, Xuan Yunpeng, Gao Bing, Sun Xiao, Miao Shuncheng, Lu Tong, Wang Yuanyong, Jiao Wenjie
Department of Thoracic Surgery, Affiliated Hospital of Qingdao University, Qingdao, China,
School of Basic Medicine, Qingdao University, Qingdao, China.
Cancer Manag Res. 2018 Sep 10;10:3383-3392. doi: 10.2147/CMAR.S173941. eCollection 2018.
Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death worldwide. The main obstacle to early diagnosis or monitoring of patients at high risk of poor survival has been the lack of essential predictive biomarkers.
RNA-sequencing was performed on LUAD affected tissue and paired adjacent to noncancerous tissue samples and Gene Expression Omnibus dataset GSE19188 and GSE33532 were used to obtain an intersection of differential expressed genes and construct a protein-protein interaction network to get hub genes. Then corresponding overall survival information of two cohorts of LUAD patients from our hospital and The Cancer Genome Atlas project-LUAD were included in the present study. An analysis of the Kyoto Encyclopedia of Genes and Genomes database and Gene Ontology were carried out to study the signature mechanism.
In our study, we identified eight candidate genes (DLGAP5, KIF11, RAD51AP1, CCNB1, AURKA, CDC6, OIP5 and NCAPG) closely related to survival in LUAD. A linear prognostic model of the eight genes was constructed and weighted by the regression coefficient (β) from the multivariate Cox regression analysis of The Cancer Genome Atlas-LUAD cohort to divide patients into low- and high-risk groups. The prognostic ability of the signature was validated in LUAD patients at our hospital. Patients assigned to the high-risk group exhibited poor overall survival compared to patients in the low-risk group. Finally, functional enrichment analysis showed that cell division played a vital role in the development of LUAD.
The study identified an mRNA signature including eight genes, which may serve as a potential prognostic marker of LUAD.
肺腺癌（LUAD）是全球癌症相关死亡的主要原因。早期诊断或监测生存预后不良高危患者的主要障碍一直是缺乏关键的预测生物标志物。
对LUAD病变组织及配对的癌旁非癌组织样本进行RNA测序，并使用基因表达综合数据库GSE19188和GSE33532获取差异表达基因的交集，构建蛋白质-蛋白质相互作用网络以获得枢纽基因。然后纳入本院两个LUAD患者队列以及癌症基因组图谱计划-LUAD的相应总生存信息进行本研究。对京都基因与基因组百科全书数据库和基因本体进行分析以研究特征机制。
在我们的研究中，我们鉴定出八个与LUAD生存密切相关的候选基因（DLGAP5、KIF11、RAD51AP1、CCNB1、AURKA、CDC6、OIP5和NCAPG）。构建了这八个基因的线性预后模型，并根据来自癌症基因组图谱-LUAD队列多变量Cox回归分析的回归系数（β）进行加权，将患者分为低风险组和高风险组。该特征的预后能力在本院的LUAD患者中得到验证。与低风险组患者相比，分配到高风险组的患者总生存较差。最后，功能富集分析表明细胞分裂在LUAD的发生发展中起关键作用。
该研究鉴定出一个包含八个基因的mRNA特征，其可能作为LUAD的潜在预后标志物。
