An EBC/Plasma miRNA Signature Discriminates Lung Adenocarcinomas From Pleural Mesothelioma and Healthy Controls

Abstract

BackgroundDespite significant improvement in screening programs for cancers of the respiratory district, especially in at-risk subjects, early disease detection is still a major issue. In this scenario, new molecular and non-invasive biomarkers are needed to improve early disease diagnosis.MethodsWe profiled the miRNome in exhaled breath condensate (EBC) and plasma samples from fourteen patients affected by lung AdCa, nine healthy subjects. miRNA signatures were then analyzed in another neoplasia of the respiratory district, i.e. pleural mesothelioma (n = 23) and subjects previously exposed to asbestos were used as controls for this cohort (n = 19). Selected miRNAs were analyzed in purified pulmonary neoplastic or normal epithelial and stromal cell subpopulation from AdCa patients. Finally, the plasmatic miRNA signature was analyzed in a publicly available cohort of NSCLC patients for data validation and in silico analysis was performed with predicted miRNA targets using the multiMiR tool and STRING database.ResultsmiR-597-5p and miR-1260a are significantly over-expressed in EBC from lung AdCa and are associated with AdCa. Similarly, miR-1260a is also up-regulated in the plasma of AdCa patients together with miR-518f-3p and correlates with presence of lung cancer, whereas let-7f-5p is under-expressed. Analysis of these circulating miRNAs in pleural mesothelioma cases confirmed that up-regulation of miR-518f-3p, -597-5p and -1260a, is specific for lung AdCa. Lastly, quantification of the miRNAs in laser-assisted microdissected lung tissues revealed that miR-518f-3p, 597-5p and miR-1260a are predominantly expressed in tumor epithelial cells. Validation analysis confirmed miR-518f-3p as a possible circulating biomarker of NSCLC. In silico analysis of the potentially modulated biological processes by these three miRNAs, shows that tumor bioenergetics are the most affected pathways.ConclusionsOverall, our data suggest a 3-miRNAs signature as a non-invasive and accurate biomarker of lung AdCa. This approach could supplement the current screening approaches for early lung cancer diagnosis.

miRNAs in Cancer (Review of Literature)

“…Examination of miRNAs for specific fractions can significantly increase both the sensitivity and specificity of selected circulating miRNAs as noninvasive biomarkers [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ].…”

A validation study for the utility of serum microRNA as a diagnostic and prognostic marker in patients with osteosarcoma

“…The upregulation of miR-1260a was previously reported to be a biomarker of lung adenocarcinoma (40). However, the serum levels of miR-1260a were shown to be decreased in ovarian and prostate cancer and increased in the postoperative state for metastatic melanoma (41)(42)(43).…”

Plasma MicroRNAs Related to Metabolic Syndrome in Mexican Women

“…The expression of hsa-miR-1260a has been reported in smooth muscle cells [53], monocyte-derived dendritic cells [54], and in the circulation of subjects infected with the virus A influenza [55]. This c-miRNA has also been related to malignant diseases, such as breast cancer [56, 57], prostate cancer [58], melanoma [59], ovarian carcinoma [60], lung adenocarcinoma [61], and asthma [62]. According to a recent review by Fodor et al [63], miRNAs dysregulated in the MetS may have effects on tumor signaling pathways.…”