Genome-Wide Analysis of Lung Adenocarcinoma Identifies Novel Prognostic Factors and a Prognostic Score

Frontiers in Genetics

Siguang Li¹  Xi Zhang¹  Yueqiang Song¹  Chang Chen²  Donglai Chen²  Erjia Zhu²  Gening Jiang²  Fuquan Zhang³  Yongbing Chen³  Xiaofan Wang³ 

[1] Department of Regenerative Medicine, Stem Cell Center, Tongji University School of Medicine, Shanghai, China;Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China;Department of Thoracic Surgery, The Second Affiliated Hospital of Soochow University, Medical College of Soochow University, Suzhou, China;

关键词: lung adenocarcinoma;    genome-wide;    prognostic factor;    survival prediction;    TCGA;   

DOI  :  10.3389/fgene.2019.00493

来源: DOAJ

【 摘 要 】

Background and ObjectiveLung adenocarcinoma (LUAD) is the most common histological type of all lung cancers and is associated with genetic and epigenetic aberrations. The tumor, node, and metastasis (TNM) stage is the most authoritative indicator of the clinical outcome in LUAD patients in current clinical practice. In this study, we attempted to identify novel genetic and epigenetic modifications and integrate them as a predictor of the prognosis for LUAD, to supplement the TNM stage with additional information.MethodsA dataset of 445 patients with LUAD was obtained from The Cancer Genome Atlas database. Both genetic and epigenetic aberrations were screened for their prognostic impact on overall survival (OS). A prognostic score (PS) integrating all the candidate prognostic factors was then developed and its prognostic value validated.ResultsA total of two micro-RNAs, two mRNAs and two DNA methylation sites were identified as prognostic factors associated with OS. The low- and high-risk patient groups, divided by their PS level, showed significantly different OS (p < 0.001) and recurrence-free survival (RFS; p = 0.005). Patients in the early stages (stages I/II) and advanced stages (stages III/IV) of LUAD could be further subdivided by PS into four subgroups. PS remained efficient in stratifying patients into different OS (p < 0.001) and RFS (p = 0.005) when the low- and high-risk subgroups were in the early stages of the disease. However, there was only a significant difference in OS (p = 0.04) but not RFS (p = 0.2), between the low-risk and high-risk subgroups when both were in advanced stages.ConclusionPS, in combination with the TNM stage, provides additional precision in stratifying patients with significantly different OS and RFS prognoses. Further studies are warranted to assess the efficiency of PS and to explain the effects of the genetic and epigenetic aberrations observed in LUAD.

【 授权许可】

Unknown