Τίτλος:
The miR-200 family as prognostic markers in clear cell renal cell carcinoma
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Objectives: microRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by mRNA cleavage or translational repression. The miR-200 family is involved in the regulation of various tumor biologic processes including apoptosis, proliferation, invasion, and metastasis. They function mainly as tumor suppressors. In this study, we aim to validate the prognostic significance of miR-200 family using large cohort of primary clear cell renal cell carcinoma (ccRCC) and matched normal tissue and to explore the role of miR-200 family in RCC pathogenesis and progression. Materials and Methods: We analyzed the expression of 3 members of the miR-200 family; miR-141, miR-200b, and miR-200c, between primary ccRCC, matched normal renal tissues, and nonmatched metastatic RCC. We compared clinicopathologic parameter including disease-free survival to miR-200 family expression. Additionally, we validated our results using The Cancer Genome Atlas dataset. We explored functional role of these miRNAs by bioinformatics analyses. Results and Conclusions: Expression of miR-200 family significantly decreased in cancer compared to non-neoplastic tissues. miR-141 and miR-200b were significantly down-regulated in metastatic than primary tumors. There was statistically significant negative association between all 3 miRNAs and tumor size and stage. As binary variables, univariate analyses revealed that miR-141, miR-200b, and miR-200c-positive ccRCC patients have a statistically significant lower chance of disease-recurrence or relapse and multivariate analyses showed miR-200b and miR-200c-positive patients have longer disease-free survival. We could predict disease-free survival better when 2 or more miRNAs were used as a combination. Overall survival analysis using The Cancer Genome Atlas data revealed that miR-200b-positive patients have significantly better survival. These results suggest that miR-141, miR-200b, and miR-200c are independent prognostic markers for ccRCC. Targets of these miRNAs are associated with pathways related to cancer invasion and metastasis, including TRAIL pathway, VEGF and VEGFR signaling network, and epithelial-mesenchymal transition. © 2019 Elsevier Inc.
Συγγραφείς:
Saleeb, R.
Kim, S.S.
Ding, Q.
Scorilas, A.
Lin, S.
Khella, H.W.
Boulos, C.
Ibrahim, G.
Yousef, G.M.
Περιοδικό:
Urologic Oncology: Seminars and Original Investigations
Εκδότης:
HANLEY & BELFUS-ELSEVIER INC
Λέξεις-κλειδιά:
glypican 1; microRNA 141; microRNA 200; microRNA 200b; microRNA 200c; vasculotropin; vasculotropin receptor; microRNA; MIRN141 microRNA, human; MIRN200 microRNA, human; tumor marker, Article; cancer growth; cancer prognosis; cancer recurrence; cancer size; cancer staging; cancer survival; carcinogenesis; cohort analysis; controlled study; copy number variation; disease free survival; down regulation; epithelial mesenchymal transition; female; gene expression; human; human tissue; major clinical study; male; metastasis; overall survival; priority journal; protein expression; real time polymerase chain reaction; real time reverse transcription polymerase chain reaction; recurrent disease; renal cell carcinoma; retrospective study; aged; biology; cell motion; disease exacerbation; follow up; gene expression regulation; genetics; information processing; kidney; kidney tumor; metabolism; middle aged; mortality; nephrectomy; pathology; prognosis; renal cell carcinoma, Aged; Biomarkers, Tumor; Carcinoma, Renal Cell; Cell Movement; Computational Biology; Datasets as Topic; Disease Progression; Disease-Free Survival; Down-Regulation; Epithelial-Mesenchymal Transition; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Humans; Kidney; Kidney Neoplasms; Male; MicroRNAs; Middle Aged; Neoplasm Staging; Nephrectomy; Prognosis
DOI:
10.1016/j.urolonc.2019.08.008
