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

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111 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 7 2012

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ASJC Scopus subject areas

  • Cancer Research

Cite this

Lu, Y., Govindan, R., Wang, L., Liu, P. Y., Goodgame, B., Wen, W., Sezhiyan, A., Pfeifer, J., Li, Y. F., Hua, X., Wang, Y., Yang, P., & You, M. (2012). MicroRNA profiling and prediction of recurrence/relapse-free survival in stage I lung cancer. Carcinogenesis, 33(5), 1046-1054. https://doi.org/10.1093/carcin/bgs100