Low let-7d and high miR-205 expression levels positively influence HNSCC patient outcome View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-12

AUTHORS

Tomasz Kolenda, Kacper Guglas, Anna Teresiak, Renata Bliźniak, Katarzyna Lamperska

ABSTRACT

INTRODUCTION: Head and neck squamous carcinoma (HNSCC) is one of the most invasive types of cancer with high mortality. A previous study has indicated that low levels of let-7d and miR-205 in HNSCC patients are correlated with poor survival. Let-7d and miR-205 are tumor suppressors and regulators of epithelial-to-mesenchymal transition (EMT). However, it is unclear if let-7d and miR-205 together influence cancer cells. AIM: To determine if let-7d and miR-205 expression levels influence HNSCC patient outcome. METHODS: The TCGA expression data for let-7d, miR-205 and their targets as well as clinical data were downloaded from cBioPortal and starBase v2.0 for 307 patients. The expression levels of let-7d and miR-205 were verified according to clinicopathological parameters. The let-7d and miR-205 high- and low-expression groups as well as disease-free survival (DFS), overall survival (OS) and expression levels of genes related to EMT, cancer stem cells, metastasis, cell cycle, drug response and irradiation response were investigated. RESULTS: Let-7d and miR-205 were frequently upregulated in HNSCC compared to normal samples, and ROC analysis showed high discrimination ability for let-7d and miR-205 (area 0.7369 and 0.7739, respectively; p < 0.0001). Differences between expression levels of let-7d or miR-205 and grade, angiolymphatic invasion, perineural invasion and alcohol consumption were indicated. No differences were observed in N-stage, tumor localization, gender or patient age. Patients with lower let-7d levels and higher miR-205 levels had significantly better OS (p = 0.0325) than patients with higher let-7d levels and lower miR-205 levels. In the low let-7d level and high miR-205 level group, a lower percentage of more advanced cancers was observed. The analysis of genes related to EMT, cancer stem cells, metastasis, cell cycle, drug response and irradiation response revealed a distinct phenotype of analyzed groups. CONCLUSIONS: The present findings indicated that let-7d down-regulation and miR-205 overexpression create a unique cell phenotype with different behavior compared to cells with upregulated let-7d and down-regulated miR-205. Thus, let-7d and miR-205 are good candidates for new HNSCC biomarkers. More... »

PAGES

17

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12929-019-0511-3

DOI

http://dx.doi.org/10.1186/s12929-019-0511-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112089060

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30755200


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49 schema:description INTRODUCTION: Head and neck squamous carcinoma (HNSCC) is one of the most invasive types of cancer with high mortality. A previous study has indicated that low levels of let-7d and miR-205 in HNSCC patients are correlated with poor survival. Let-7d and miR-205 are tumor suppressors and regulators of epithelial-to-mesenchymal transition (EMT). However, it is unclear if let-7d and miR-205 together influence cancer cells. AIM: To determine if let-7d and miR-205 expression levels influence HNSCC patient outcome. METHODS: The TCGA expression data for let-7d, miR-205 and their targets as well as clinical data were downloaded from cBioPortal and starBase v2.0 for 307 patients. The expression levels of let-7d and miR-205 were verified according to clinicopathological parameters. The let-7d and miR-205 high- and low-expression groups as well as disease-free survival (DFS), overall survival (OS) and expression levels of genes related to EMT, cancer stem cells, metastasis, cell cycle, drug response and irradiation response were investigated. RESULTS: Let-7d and miR-205 were frequently upregulated in HNSCC compared to normal samples, and ROC analysis showed high discrimination ability for let-7d and miR-205 (area 0.7369 and 0.7739, respectively; p < 0.0001). Differences between expression levels of let-7d or miR-205 and grade, angiolymphatic invasion, perineural invasion and alcohol consumption were indicated. No differences were observed in N-stage, tumor localization, gender or patient age. Patients with lower let-7d levels and higher miR-205 levels had significantly better OS (p = 0.0325) than patients with higher let-7d levels and lower miR-205 levels. In the low let-7d level and high miR-205 level group, a lower percentage of more advanced cancers was observed. The analysis of genes related to EMT, cancer stem cells, metastasis, cell cycle, drug response and irradiation response revealed a distinct phenotype of analyzed groups. CONCLUSIONS: The present findings indicated that let-7d down-regulation and miR-205 overexpression create a unique cell phenotype with different behavior compared to cells with upregulated let-7d and down-regulated miR-205. Thus, let-7d and miR-205 are good candidates for new HNSCC biomarkers.
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