Differential microRNA Expression Profile between Young and Old Lung Adenocarcinoma Patients

Background Lung cancer is the leading cause of cancer related mortality and approximately 80% is represented by non-small cell lung cancer (NSCLC). In the last decade, age of patients at diagnosis has decreased, with an incidence of approximately 13.4% in patients under 50 years. Previous studies have hypothesized that lung cancer in young patients could represent a separated clinicalpathological entity; however it is still controversial whether younger patients have a different outcome compared with their older counterparts. MicroRNAs (miRNAs) have recently been defined to play a key role in cancer pathogenesis and their aberrant expression has been suggested as a potential biomarker of prognosis in lung adenocarcinoma. To understand the molecular features of young and old adenocarcinoma patients, we investigated the expression levels of a panel of miRNAs selected from recent literature. Methods Thirty-five lung ADC from patients under 50 years old were enrolled as the younger group and thirty-five ADC older than 50 years were collected as the older group. After miRNA isolation from formalin-fixed and paraffin-embedded tumor tissues, the expression levels of 30 miRNAs were analyzed by NanoString technology and compared between the two groups. Survival data were used to assess the prognostic impact of miRNAs. The software miRgator v3.0 was used to predict the putative pathways targeted by miRNAs. Results The analysis revealed that 7 miRNAs (miR-25-3p, miR-29c-3p, miR-33a-5p, miR-144-3p, miR-153-3p, miR-342-5p and miR-485-3p) were differently expressed in the two groups (Mann-Whitney U test, p<0.05). All these miRNAs showed higher expression levels in young compared to old patients, and their predicted targets included EGFR, MET, VEGF-A,TP53 and PDGFRa. miR-144-3p had an opposite influence on overall survival, since its upregulation was associated with a better outcome in young patients (p= 0.01) and a worse prognosis in the old group (p= 0.03). Conclusion Our study provides new insights about the role of miRNAs in lung adenocarcinoma occurring in young patients. We observed that lung cancer in young and old patients may be influenced by different regulatory mechanisms since we found 7 miRNAs as downregulated in the older group, probably due to distinct age-related genetic and epigenetic alterations. Moreover, one of the deregulated miRNAs showed a different prognostic impact in the two groups thus confirming that young and old patients deserve a specific clinical approach. Further validations are needed to better define if an age-based genomic signature could be used as prognostic marker in lung cancer.