Distinct Angiogenic microRNA-mRNA Expression Profiles Among Subtypes of Lung Adenocarcinoma

Adenocarcinoma (ADC) represents the most common histological type of non-small cell lung cancer (NSCLC), with a heterogeneous pattern of growth classified as lepidic, acinar, papillary, solid, and micropapillary. For ADC patients there are few available therapeutic options and a valuable therapeutic strategy is represented by angiogenesis inhibitors; however, new reliable biomarkers to identify patients with benefit from anti-angiogenic drugs are needed. We designed a panel of sixteen miRNAs together with six their mRNA targets involved in the angiogenesis pathway and expression analysis was performed by the nCounter System (R) (NanoString Technologies) in 88 ADC patients: 29 were predominantly lepidic (33%), 26 solid (29.5%), 22 acinar (25%), and for 11 patients the prevalent pattern was papillary (12.5%). When we compared mRNA expression levels with the different histological ADC subtypes we found a significant higher expression of VEGF in papillary and solid than in other subtypes (p = 0.008). Among 16 miRNAs that target the angiogenic mRNA, 4 were significantly downregulated in papillary/solid compared to other groups. Our data suggest a distinct angiogenic miRNA-mRNA expression profile among the subtypes of ADC, with a putative clinical application to stratify patients for anti-angiogenetic drugs. Moreover, the regulation of angiogenic mRNA factors by miRNAs could provide a novel therapeutic approach based on their expression pattern specific for distinct ADC subtypes. Further studies are needed in a larger cohort of patients to confirm our results.