Identification of molecular markers using integrative analysis involving genomic a...
| Full text | |
| 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]
Total Authors: 8
|
| 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
Total Affiliations: 6
|
| 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 type: | Research Projects - Thematic Grants |