Identification of miR-203a, mir-10a, and miR-194 as predictors for risk of lymphovascular invasion in head and neck cancers

Abstract

Lymphovascular invasion (LVI) is an important prognostic indicator of lymph node metastasis and disease aggressiveness but clear molecular mechanisms mediating this in head and neck cancers (HNSC) remain undefined. To identify important microRNAs (miRNAs) in HNSC that associate with and are also predictive of increased risk of LVI, we used a combination of clustering algorithms, multiple regression analyses and machine learning approaches and analyzed miRNA expression profiles in the TCGA HNSC database. As the first step, we identified miRNAs with increased association with LVI as a binary variable. In order to determine whether the identified miRNAs would show functional clusters that are also indicative of increased risk for LVI, we carried out unsupervised as well as supervised clustering. Our results identified distinct clusters of miRNAs that are predictive of increased LVI. We further refined these findings using a Random forest approach, and miR-203a-3p, mir-10a-5p, and miR-194-5p to be most strongly associated with LVI. Pathway enrichment analysis showed these miRNAs targeted genes involved in Hippo signaling and fatty acid oxidation pathways that are mediators of lymph node metastasis. Specific association was also identified between the miRNAs associated with LVI and expression of several lymphangiogenic genes that could be critical for determination of therapeutic strategies.

Epidemiological, Clinical, and Genomic Profile in Head and Neck Cancer Patients and Their Families

“…Three patients (2.1, 26.1, and 207) presented gains covering MIR genes ( MIR1256 , MIR548F1 , and MIR574 , respectively). MIRs act in the gene regulation and have been previously associated with HNC [ 39 , 40 ]. These three miRNAs ( MIR1256 , MIR548 , and MIR574 ) have also been related to cancer progression in gastric, thyroid, and brain cancer [ 41 , 42 , 43 ].…”

miR‐203a—A multifaceted regulator modulating cancer hallmarks and therapy response

“…59 The tissues and cell lines tested for CRC had a poor prognosis for miR-203a downregulation. 58 In HNSCC, miR-203a-3p, along with two other miRNAs, are identified as a prognostic marker for lymph-node invasion, 85 and its expression was associated with the rate of invasiveness of BLCA. 84 Further in HCC patients, miR-203a expression acts as a diagnostic marker.…”