MicroRNA profiling and prediction of recurrence/relapse-free survival in stage I lung cancer

Yan Lu, Ramaswamy Govindan, Liang Wang, Peng Yuan Liu, Boone Goodgame, Weidong Wen, Ananth Sezhiyan, John Pfeifer, Ya Fei Li, Xing Hua, Yian Wang, Ping Yang, Ming You

Research output: Contribution to journalArticlepeer-review

136 Scopus citations

Abstract

About 30% stage I non-small cell lung cancer (NSCLC) patients undergoing resection will recur. Robust prognostic markers are required to better manage therapy options. MicroRNAs (miRNAs) are a class of small non-coding RNAs of 19-25 nt and play important roles in gene regulation in human cancers. The purpose of this study is to identify miRNA expression profiles that would better predict prognosis of stage I NSCLC. MiRNAs extracted from 527 stage I NSCLC patients were profiled on the human miRNA expression profiling v2 panel (Illumina). The expression profiles were analyzed for their association with cancer subtypes, lung cancer brain metastasis and recurrence/relapse free survival (RFS). MiRNA expression patterns between lung adenocarcinoma and squamous cell carcinoma differed significantly with 171 miRNAs, including Let-7 family members and miR-205. Ten miRNAs associated with brain metastasis were identified including miR-145*, which inhibit cell invasion and metastasis. Two miRNA signatures that are highly predictive of RFS were identified. The first contained 34 miRNAs derived from 357 stage I NSCLC patients independent of cancer subtype, whereas the second containing 27 miRNAs was adenocarcinoma specific. Both signatures were validated using formalin-fixed paraffin embedded and/or fresh frozen tissues in independent data set with 170 stage I patients. Our findings have important prognostic or therapeutic implications for the management of stage I lung cancer patients. The identified miRNAs hold great potential as targets for histology-specific treatment or prevention and treatment of recurrent disease.

Original languageEnglish (US)
Pages (from-to)1046-1054
Number of pages9
JournalCarcinogenesis
Volume33
Issue number5
DOIs
StatePublished - May 2012

ASJC Scopus subject areas

  • Cancer Research

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