Prognostic value of microRNA expression in operable non-small cell lung cancer patients.
BACKGROUND
About 50% of non-small cell lung cancer (NSCLC) patients develop distant metastases following pulmonary resection. Currently, there are no reliable factors allowing for individual selection of high-risk patients for adjuvant systemic therapies.


METHODS
We assessed by quantitative reverse transcription PCR microRNA (miRNA) expression in 273 stage I-IIIA NSCLC samples. Expression of 677 miRNAs was evaluated in fresh-frozen tumour samples in the training cohort of 50 squamous cell carcinoma (SCC) patients who underwent curative surgery. Of those, 20 patients developed distant metastases, and 30 were free of recurrence for >4 years. In the second step, miRNAs with highest predictive value for distant relapse were re-evaluated in formalin-fixed paraffin-embedded material in an independent group of 134 stage I-IIIA SCC patients. Additionally, the same miRNAs were investigated in 89 lung adenocarcinoma (AC) patients and in normal lung parenchyma (NLP).


RESULTS
In the training cohort of SCC, six miRNAs were differently expressed in the non-recurrent vs recurrent groups and correlated with distant recurrence-free survival, however none reached the level of significance after correction for multiple testing. Of these six miRNAs, miR-662, -192 and -192* were confirmed as prognostic in the independent SCC cohort. Expression of miR-128, -10b, -502-3p and -192 differed between SCC and AC, and miR-128 and -192 - between NLP and NSCLC.


CONCLUSIONS
We identified three new miRNAs predictive of distant relapse in operable SCC. Future miRNA studies should account for differences between NSCLC subtypes.
Department of Oncology and Radiotherapy Medical University of Gdansk, ul. Dębinki 7, 80-211 Gdańsk, Poland.
M
M
Skrzypski
Department of Pathology Medical University of Gdansk, ul. Smoluchowskiego 17, 80-214 Gdańsk, Poland.
P
P
Czapiewski
Department of Genetics Maria Sklodowska-Curie Memorial Cancer Centre, ul. Roentgena 5, 02-781, Warsaw, Poland.
K
K
Goryca
Department of Pulmonology and Allergology Medical University of Gdansk, ul. Dębinki 7, 80-211 Gdańsk, Poland.
E
E
Jassem
Laboratory of Bioinformatics and Biostatistics Maria Sklodowska-Curie Memorial Cancer Center, ul. Roentgena 5, 02-781 Warsaw, Poland.
L
L
Wyrwicz
Department of Forensic Medicine Medical University of Gdańsk, ul. Dębowa 23, 80-204 Gdańsk, Poland.
R
R
Pawłowski
Department of Thoracic Surgery Medical University of Gdansk, ul. Smoluchowskiego 17, 80-214 Gdańsk, Poland.
W
W
Rzyman
Department of Pathology Medical University of Gdansk, ul. Smoluchowskiego 17, 80-214 Gdańsk, Poland.
W
W
Biernat
Department of Oncology and Radiotherapy Medical University of Gdansk, ul. Dębinki 7, 80-211 Gdańsk, Poland.
J
J
Jassem
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D055815:Young Adult
D014408:Biomarkers, Tumor; D035683:MicroRNAs