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MiR-7 methylation as a biomarker to predict poor survival in early-stage non-small cell lung cancer patients.

ABSTRACT: Non-small-cell lung cancer (NSCLC) is the most common malignancy worldwide. Platinum-based chemotherapy is the standard of care for these patients. Recent research showed that miR-7 methylation status is a biomarker of cisplatin resistance in lung and ovarian cancer cells, which is one of the major limitations associated with their clinical management. The aim of the present study is to provide clinical insights associated with this novel potential biomarker in NSCLC patients by comparing the miR-7 methylation status with the cisplatin treatment response. Our results analyzed in 81 samples show that miR-7 methylation is a common event in tumor tissue and it is more frequent as the stage of the disease advances, remaining in 75% of metastatic patients. Tumor miR-7 unmethylation trend to a better PFS in early stages, and when our data was validated in an extended "in silico" cohort of 969 patients we obtained a significant increment in PFS and OS in those patients harboring miR-7 unmethylated (p?=?0.010 and p?=?0.007 respectively). When we select those early-stages patients harbouring miR-7 methylation, we observed that adenocarcinoma patients present a dramatic decrease in PFS compared with squamous cell carcinoma patients (median 18.9 versus 59.7 months, p?=?0.002). In conclusion, our results show that presence of miR-7 methylation in early-stage NSCLC is suggestive of aggressive behavior, especially for adenocarcinoma patients. One major challenge in early diagnosis in NSCLC is identify the subgroup of patients that could benefit for adjuvant therapy, our data establish the basis for epigenetic classification on early-stage NSCLC that could influence treatment decisions in the future.

SUBMITTER: Rodriguez-Antolin C

PROVIDER: S-EPMC6686393 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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miR-7 methylation as a biomarker to predict poor survival in early-stage non-small cell lung cancer patients.

Rodríguez-Antolín Carlos C Felguera-Selas Laura L Pernía Olga O Vera Olga O Esteban Isabel I Losantos García Itsaso I de Castro Javier J Rosas-Alonso Rocío R Ibanez de Caceres Inmaculada I

Cell & bioscience 20190807

Non-small-cell lung cancer (NSCLC) is the most common malignancy worldwide. Platinum-based chemotherapy is the standard of care for these patients. Recent research showed that miR-7 methylation status is a biomarker of cisplatin resistance in lung and ovarian cancer cells, which is one of the major limitations associated with their clinical management. The aim of the present study is to provide clinical insights associated with this novel potential biomarker in NSCLC patients by comparing the mi ...[more]

PMID: 31406565

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Project description:BACKGROUND:Several treatments in non-small cell lung cancer (NSCLC) are histology-dependent, and the need for histology-related markers is increasing. MicroRNAs (miRNAs) are promising molecular markers in multiple cancers and show differences in expression depending on histological subtype. The miRNA family miR-200 has been associated with the regulation of epithelial-mesenchymal (EMT)/mesenchymal-epithelial transition (MET). EMT involves profound phenotypic changes that include the loss of cell-cell adhesion, the loss of cell polarity, and the acquisition of migratory and invasive properties that facilitates metastasis. A dual role for the miR-200 family in the prognosis of several tumors has been related to tumor cell origin. However, the prognostic role and function of miR-200 family in early-stage NSCLC adenocarcinoma and squamous cell carcinoma (SCC) have not been well established. METHODS:miRNA expression was determined using TaqMan assays in 155 tumors from resected NSCLC patients. Functional studies were conducted in three NSCLC cell lines: H23, A-549 and HCC-44. RESULTS:High miR-200c expression was associated with shorter overall survival (OS) in the entire cohort (p?=?0.024). High miR-200c (p?=?0.0004) and miR-141 (p?=?0.009) expression correlated with shorter OS in adenocarcinoma - but not in SCC. In the multivariate analysis, a risk score based on miR-141 and miR-200c expression emerged as an independent prognostic factor for OS in the entire cohort (OR, 2.787; p?=?0.033) and in adenocarcinoma patients (OR, 10.649; p?=?0.002). Functional analyses showed that miR-200c, was related to mesenchymal-epithelial transition (MET) and affected cell migration and E-cadherin levels, while overexpression of miR-141 reduced KLF6 protein levels and produced an increase of secretion of VEGFA in vitro (H23, p?=?0.04; A-549, p?=?0.03; HCC-44, p?=?0.02) and was associated with higher blood microvessel density in patient tumor samples (p<0.001). CONCLUSION:High miR-141 and miR-200c expression are associated with shorter OS in NSCLC patients with adenocarcinoma through MET and angiogenesis.

Dataset Information

MiR-7 methylation as a biomarker to predict poor survival in early-stage non-small cell lung cancer patients.

Publications

miR-7 methylation as a biomarker to predict poor survival in early-stage non-small cell lung cancer patients.

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