title: MicroRNA profiling and prediction of recurrence/relapse-free survival in stage I lung cancer.
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.
authors.affiliation: Department of Physiology and Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Govindan
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Peng-yuan
authors.initials: PY
authors.lastname: Liu
authors.forename: Boone
authors.initials: B
authors.lastname: Goodgame
authors.forename: Weidong
authors.initials: W
authors.lastname: Wen
authors.forename: Ananth
authors.initials: A
authors.lastname: Sezhiyan
authors.forename: John
authors.initials: J
authors.lastname: Pfeifer
authors.forename: Ya-fei
authors.initials: YF
authors.lastname: Li
authors.forename: Xing
authors.initials: X
authors.lastname: Hua
authors.forename: Yian
authors.initials: Y
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Ming
authors.initials: M
authors.lastname: You
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012008:Recurrence
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs