miRNA expression profiling of lung adenocarcinomas: correlation with mutational status.
MicroRNA (miRNA) expression is deregulated in lung cancer, and some miRNAs are associated with poor prognosis and survival. In this study, we investigated the miRNA expression in lung adenocarcinomas with different oncogenic mutations, including EGFR-positive, KRAS-positive and EGFR/KRAS-negative tumors. The expression of 319 miRNAs was evaluated by Exiqon/Luminex microarray, and expression of individual miRNAs was validated by individual RT-PCR assays (Applied Biosystems). Overall, miRNA expression was similar among three mutationally different groups with most upregulated miRNAs being miR-20a, miR-328, miR-34c and miR-18b and most downregulated miRNAs being miR-32, miR-137 and miR-342. Four miRNAs (miR-155, miR-25, miR-495 and miR-7g) were expressed differently among these tumors. miR-155 was upregulated only in EGFR/KRAS-negative group, miR-25 was upregulated only in EGFR-positive group and miR-495 was upregulated only in KRAS-positive adenocarcinomas. In opposite, let-7g was downregulated in all three groups, with more significant downregulation in EGFR/KRAS-negative adenocarcinomas. Principal component analysis (PCA) revealed significant correlation between miRNA expression patterns and somatic mutations. In this study, we demonstrated that despite the similarity in miRNA expression among lung adenocarcinomas with different somatic mutations, some miRNAs showed unique expression patterns, which were in strong correlation with the mutation type, suggesting different carcinogenic pathway for these tumors. These miRNAs can be further explored for their diagnostic and prognostic use.
Dacic
Sanja
S
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. dacics@upmc.edu
Kelly
Lindsey
L
Shuai
Yongli
Y
Nikiforova
Marina N
MN
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D004252:DNA Mutational Analysis; D015870:Gene Expression; D020869:Gene Expression Profiling; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics*; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D020133:Reverse Transcriptase Polymerase Chain Reaction; D018631:ras Proteins / Q000235:genetics
D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins