Comprehensive Analysis of Pulmonary Adenocarcinoma In Situ (AIS) Revealed New Insights into Lung Cancer Progression

摘要

Pulmonary adenocarcinoma in situ (AIS) is an intermediate subtype of lung adenocarcinoma that exhibits non-invasive growth patterns, but can develop into invasive. Almost 100% of AIS patients can be cured with complete resection. In contrast, the five-year survival rate for those diagnosed with invasive lung adenocarcinoma is only about 4%. In order to get a better understanding of adenocarcinoma and identify marks indicating its evaluation and progression, what needs to be done is a genome-wide evaluation of the disease. In this study, we used RNA-seq data from normal, AIS, and invasive lung cancer samples to identify gene module with differential gene expressions that represents the properties of AIS, distinct from normal and invasive tumor. Utilizing the differential expression patterns of protein-coding genes and long non-coding RNAs (IncRNAs) between AIS and other conditions, we obtained a small group of 72 AIS-specific genes consisting 41 protein-coding genes, 5 annotated lncRNAs, and 26 novel IncRNA transcripts that expressed specifically in AIS samples. We consider that twelve of the protein-coding genes are lung cancer driver genes with located driver somatic mutations. Moreover, these AIS-specific genes show capabilities (98% accuracy in an independent data set) for indicating early stage lung cancer and normal situations. These genes are determined based on cell-adhesion functioning, including angiogenesis and fibronectin, etc., that are highly related to cancer development. The comparison of AIS with normal and invasive tumor provides the gene list revealing the mechanisms that accounts for AIS progression to invasive cancer. Furthermore we identified important signatures contributing to the early diagnosis of lung cancer, providing auxiliary studies to our ongoing precision medicine research (http://americancse.org/events/csce2017/keynotes_lectures/yang_talk).