Abstract
Background: Early detection of lung cancer could increase survival and curation rate as low stage and surgery are positive prognostic factors. Screening of ever-smokers and asbestos exposed individuals by non-invasive methods is a desired path to increase the rate of early detection and cure in the future. Moreover, circulating early microRNA signature may decipher lung cancer biology. Methods: Serum samples from the HUNT3 Biobank, Levanger, Norway were profiled with separate total microRNA sequencing (Illumina). The samples included lung adenocarcinoma (n=4), squamous cell carcinoma (n=5) and small-cell carcinoma (n=5) cases collected 1-4 years before diagnosis, along with age and sex-matched non-cancer individuals (n=28), ratio 1:2; the never smokers to ever-smokers ratio of controls was 50/50. The differentially expressed (DE) microRNAs were analyzed for enrichment by DIANA-miRPath v3. 0. The target genes of each microRNA included in the signature were determined with the DIANA-microT web server v5.0 and the union of all the microRNA targets was assessed for enrichment in KEGG pathways. Pathways with FDR-corrected p-value < 0.05 are reported in the results. Results: We detected 12 DE microRNAs in the serum 1-4 years in adenocarcioma plus squamous cell carcinoma (NSLC) versus controls. There were 9 DE microRNAs small-cell carcinoma. Several pathways were enriched, including pathways for their respective cancer types (Ex. Table1). Conclusions: In this relatively small but unique pilot study we identified microRNAs that were significantly DE in serum of lung cancer patient 1-4 years prior to diagnosis. These specific microRNAs also target cancer-specific pathways. These are preliminary results whose validation in a larger cohort is still pending. There is hope that significant biomarkers can soon be discovered for early detection of lung cancer within the microRNA family.
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