Integrated miRNA and mRNA expression analysis uncovers drug targets in laryngeal squamous cell carcinoma patients

Author(s)

Lopez Lapa, Rainer Marco ^{[1, 2]} ; Barros-Filho, Mateus Camargo ^[1] ; Marchi, Fabio Albuquerque ^[1] ; Custodio Domingues, Maria Aparecida ^[3] ; de Carvalho, Genival Barbosa ^[4] ; Drigo, Sandra Aparecida ^[5] ; Kowalski, Luiz Paulo ^[4] ; Rogatto, Silvia Regina ^{[5, 6]}

Affiliation

^[1] CIPE AC Camargo Canc Ctr, Int Res Ctr, Sao Paulo - Brazil

^[2] Sao Paulo State Univ UNESP, Dept Genet, Inst Biosci, Botucatu, SP - Brazil

^[3] Sao Paulo State Univ UNESP, Dept Pathol, Fac Med, Botucatu, SP - Brazil

^[4] AC Camargo Canc Ctr, Dept Head & Neck Surg & Otorhinolaryngol, Sao Paulo - Brazil

^[5] Sao Paulo State Univ UNESP, Dept Surg & Orthoped, Fac Med, Botucatu, SP - Brazil

^[6] Univ Southern Denmark, Dept Clin Genet, Vejle Hosp, Inst Reg Hlth Res, Vejle - Denmark

• Document type: Journal article
• Source: Oral Oncology; v. 93, p. 76-84, JUN 2019.
• Web of Science Citations: 1

Abstract

Objectives: The current treatment of laryngeal squamous cell carcinoma (LSCC) is based on radical surgery and radiotherapy resulting in high morbidity. Chemoradiotherapy has been used as alternative to organ sparing; however, several advanced cases presented resistance to treatment, which contributes to a high risk of recurrence and mortality. Coding RNAs and miRNAs have potential to be used as biomarkers or targets for cancer therapy. Materials and Methods: In this study, 36 LSCC and 5 non-neoplastic control samples were investigated using miRNA and mRNA large-scale expression analysis and a cross-validation was performed using the TCGA database (116 LSCC and 12 surrounding normal tissues). Results: The large-scale profiling revealed the involvement of 28 miRNAs and 817 genes differentially expressed in LSCC. An integrative analysis comprising predicted and experimentally validated miRNA/mRNA interactions (negatively correlated), resulted in 28 miRNAs and 543 mRNAs. Decreased expression of miR-199b was significantly associated with shorter disease-free survival in LSCC (internal and TCGA datasets). The expression levels of selected miRNAs (miR-199b-5p, miR-29c-3p, miR-204-5p, miR-125b-5p and miR-92a-3p) and genes (COL3A1, COL10A1, ERBB4, HMGA2, HLF, TOP2A, MMP3, MMP13, MMP10 and PPP1R3) were confirmed as altered in LSCC by RT-qPCR. Additionally, a drug target prediction analysis revealed drug combinations based on miRNA and mRNA expression, pointing out novel alternatives to optimize the LSCC treatment. Conclusion: Collectively, these findings provide new insights in the LSCC transcriptional deregulation and potential drug targets. (AU)

• FAPESP's process: 08/57887-9 - National Institute of Oncogenomics
• Grantee: Luiz Paulo Kowalski
• Support Opportunities: Research Projects - Thematic Grants