MA02.05 Distinct Angiogenic microRNA-mRNA Expression Profiles among Subtypes of Lung Adenocarcinoma

Abstract

Non-small cell lung cancer (NSCLC) accounts for 80% of all lung cancers and adenocarcinoma (ADC) represents the most common histological type with a heterogeneous pattern of growth classified as lepidic, acinar, papillary, solid, and micropapillary. For ADC there are restricted available therapeutic options except for patients that could benefit from target therapy. A valuable therapeutic strategy is represented by angiogenesis inhibitors such as bevacizumab that has been approved for the treatment of NSCLC patients. However, there are concerns about its treatment-related toxicity and the identification of new reliable biomarkers to stratify patients who can really benefit from antiangiogenic drugs is urgently needed. Using miRNA target prediction tools, we selected and investigated the expression level of a panel of miRNAs together with their mRNA target involved in the angiogenesis pathway. We designed a custom codeset including probes for six genes (VEGF-A, FLT1, KDR, FLT4, PDGFRa and PDGFRb) and sixteen miRNAs. The expression analysis was performed by the nCounter System® (NanoString Technologies) directly on RNA, enriched of small RNA, purified from the formalin-fixed and paraffin-embedded tumor tissues of 80 ADC patients. Of these 25 were predominantly lepidic (31.25%), 24 were predominantly solid (30%), 20 were predominantly acinar (16%), 11 were predominatly papillary (13.75%). Comparing the expression levels of mRNAs with the different histological ADC subtypes we found a significant higher expression of VEGF-A in papillary than in other subtypes (p=0.02). In contrast PDGFRa and PDGFRb were upregulated in lepidic and downregulated in papillary subtypes (both p=0.03). Among 16 miRNAs that target the angiogenic mRNA, 6 were significantly downregulated in papillary compared to other groups. Our data suggest a distinct angiogenic miRNA-mRNA expression profile among the subtypes of ADC. The higher level of VEGF-A in papillary than in lepidic subtypes could represent a useful biomarker to stratify patients who can effectively treated with bevacizumab, which is directed against VEGF. 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 and to investigate whether different rates of response to treatment are observed among patients stratified according to the proposed biomarkers.