Dados do Trabalho

Título

PSEUDOGENE TRANSCRIPTS IN HEAD AND NECK CANCER: IN SILICO ANALYSIS

Introdução

Once considered nonfunctional, pseudogene transcripts are now known to provide valuable information for cancer susceptibility and progression, including head and neck cancer (HNC), a serious health problem worldwide. Pseudogene transcripts might interact with the promoter of the parent gene or act as a microRNA decoy, controlling gene expression and modulating malignant cell behavior. However, pseudogenes’ role in HNC remains poorly explored, while patients’ therapy resistance and poor survival rates highlight the need of finding novel molecular biomarkers.

Objetivo

We aimed to identify potential pseudogene transcripts, their interactions, and potential pathways in HNC progression and prognostic.

Método

We performed an in silico analysis from The Cancer Genome Atlas database (219 patients) to identify the most deregulated pseudogene transcripts in HNC. We built a co-expression network and gene ontology (GO) enrichment to better understand the pseudogenes interactions and pathways in HNC. Moreover, the pseudogenes prognostic value was assessed by The Kaplan Meier Plotter online database (500 patients).

Resultado

SPATA31D5P, HERC2P3, SPATA31C2, MAGEB6P1, SLC25A51P1, BAGE2, DNM1P47, SPATA31C1, ZNF733P, and OR2W5 pseudogenes were found to be the most deregulated in HNC. In the co-expression network and GO enrichment analysis, we found that NBPF25P, HSP90AB2P, ZNF658B, and DPY19L2P3 pseudogenes were associated with 12 genes known to participate in head and neck carcinogenesis (CASP8, NOTCH2, NOTCH3, TRAF3, RB1, HRAS, PTEN, CUL3, NFE2L2, EP300, IGF1R, and TP63) and may contribute to cell communication, cellular response to stress, and intracellular transport. The pseudogene DNM1P47 was associated with the tumor suppressor TP53 and may contribute to cell proliferation, response to stress, and cell death. The pseudogene HLA-H was associated with known tumor genes HLA-A and HLA-B, and may contribute to cell proliferation, regulation of the immune system and gene expression, and Wnt signaling pathway. SPATA31D5P, SPATA31C2, BAGE2, SPATA31C1, ZNF733P, and OR2W5 pseudogenes influenced relapse-free survival and overall survival of HNC patients.

Conclusão

Due to its potential for cancer diagnosis, progression, and as a therapeutic target, this approach can guide new research to HNC understanding and development of new target therapies, especially for those patients who do not respond to conventional therapies.

Palavras-chave

Head and neck cancer; pseudogene transcripts; co-expression network