MicroRNA 92a-2*: a biomarker predictive for chemoresistance and prognostic for survival in patients with small cell lung cancer.
OBJECTIVE
Although the majority of patients with small cell lung cancer (SCLC) respond to initial chemotherapy, those with disease progression at first response assessment (chemoresistance) have inferior outcomes. There is a need for predictive biomarkers to aid investigators in designing future clinical trials that better stratify patients beyond standard clinical and laboratory parameters and to identify new treatments for this patient subpopulation. We hypothesized that tumor microRNAs (miRNAs) could serve as predictive biomarkers for chemoresistance and prognostic biomarkers for survival of patients with SCLC treated with systemic chemotherapy.


METHODS
SCLC samples annotated with clinical characteristics and baseline comorbidities were available. miRNA microarray profiling was performed on diagnostic SCLC tumor samples, and analysis was performed using XenoBase, a data integration and discovery tool. Confirmation of the top 16 miRNA candidates was performed using quantitative real-time polymerase chain reaction followed by analyses to determine clinical and miRNA biomarkers associated with chemoresistance and survival.


RESULTS
miRNAs significantly associated with chemoresistance were miR-92a-2* (p = 0.010), miR-147 (p = 0.018), and miR-574-5p (p = 0.039). By stepwise multivariate analysis, only gender and miR-92a-2* contributed significantly to survival (p = 0.023) and (p = 0.015), respectively. Baseline comorbidities were not associated with chemoresistance or survival.


CONCLUSIONS
Higher tumor miR-92a-2* levels are associated with chemoresistance and with decreased survival in patients with SCLC. Tumor miR-92a-2* may have application in screening patients with SCLC at risk for de novo chemoresistance in an effort to design more tailored clinical trials for this subpopulation. Further validation in independent sample sets is warranted.
Ranade
Aarati R
AR
Cancer and Cell Biology, Translational Genomics Research Institute, Phoenix, USA.
Cherba
David
D
Sridhar
Shravan
S
Richardson
Patrick
P
Webb
Craig
C
Paripati
Anoor
A
Bowles
Brad
B
Weiss
Glen J
GJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D015897:Comorbidity; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D015996:Survival Rate; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D012334:RNA, Neoplasm