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.

Reactivation of epigenetically silenced miR-512 and miR-373 sensitizes lung cancer cells to cisplatin and restricts tumor growth

“…In line with our results, profiling of miR expression in 357 stage I non-small cell lung cancer patients identified miR-512 as an indicator of good prognosis. 43 High miR-512 expression was associated with better prognosis regardless of cancer subtype. In addition, miR-512 was predictive of better relapse-free survival of lung adenocarcinoma patients.…”

Transcriptomic Analysis of Peripheral Blood Mononuclear Cells in Rapid Progressors in Early HIV Infection Identifies a Signature Closely Correlated with Disease Progression

“…U1 and U6 were used in the training cohort and RNY3 and U6 were used in the validation cohort for normalization. The variation of changes in the threshold cycle (⌬CT) (CT, target-CT, and control) was evaluated and used as a relative qualitative value for further assay (22 ). Preprocessing of raw data and statistical analyses were performed using RealTime StatMiner software.…”

microRNA: New Players in Metastatic Process

“…In another study, based on miRNA expression profiling of lung adenocarcinoma and SQ, ten miRNAs (hsa-miR-450b-3p, hsa-miR-29c*, hsa-miR-145*, hsamiR-148a*, hsa-miR-1, hsa-miR-30d, hsa-miR-187, hsa-miR-218, hsa-miR-708* and hsa-miR-375) associated with brain metastasis were identified including miR-145*, which inhibit cell invasion and metastasis. Two miRNA signatures that are highly predictive of recurrence free survival of 357 stage I NSCLC were also identified, one independent of cancer subtype, the other specific for adenocarcinoma or SQ subtype [131]. From a small cohort of 20 NSCLC patients, Donnem and co-workers [132] in addition to miR differentially expressed between NSCLC tumors and normal control, found 37 miRs up/down regulated in tumors derived from patients with short versus long disease specific survival (DSS) including upregulated miR-31, miR-183, let-7a, miR-193b and downregulated miR-205, miR-378, miR-708 and miR-29c.…”