The protective value of miR-204-5p for prognosis and its potential gene network in various malignancies: a comprehensive exploration based on RNA-seq high-throughput data and bioinformatics

Purpose: The prognostic role of miR-204-5p (previous ID: miR-204) is varied and inconclusive in diverse types of malignant neoplasm. Therefore, the purposes of the study comprehensively explore the overall prognostic role of miR-204-5p based on high-throughput microRNA sequencing data, and to investigate the potential role of miR-204-5p via bioinformatics approaches.

Materials and methods: The data of microRNA sequencing and survival were downloaded from The Cancer Genome Atlas (TCGA), and the prognostic value of miR-204-5p was analyzed by using Kaplan-Meier and univariate cox regressions. Then a meta-analysis was conducted with all TCGA data and relevant studies collected from literature. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. The prospective molecular mechanism of miR-204-5p was also assessed at a functional level with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-to-protein interactions (PPI) network.

Results: From TCGA data, the prognostic value of miR-204-5p obviously varied among 20 types of cancers. The pooled HR was 0.928 (95% CI: 0.774-1.113, P = 0.386, 6203 cases of malignancies). For the meta-analysis based on 15 studies from literature, the pooled HR was 0.420 (95% CI: 0.306-0.576, P < 0.001, 1783 cases of malignancies) for overall survival (OS). Furthermore, the combined HR from both TCGA and literature was 0.708 (95% CI: 0.600-0.834, P < 0.001, 7986 cases of malignancies). Subgroup analyses revealed that miR-204-5p could act as a prognostic marker in cancers of respiratory system and digestive system. Functional analysis was conducted on genes predicted as targets (n = 2057) after the overlay genes from six out of twelve software were extracted. Two significant KEGG pathways were enriched (hsa04360: Axon guidance and hsa04722: Neurotrophin signaling pathway). PPI network revealed some hub genes/proteins (CDC42, SOS1, PIK3R1, MAPK1, PLCG1, ESR1, MAPK11, and AR).

Conclusions: The current study demonstrates that over-expression of miR-204-5p could be a protective factor for a certain group of cancers. Clinically, the low miR-204-5p level could gain a predictive value for a poor survival in cancers of respiratory system and digestive system. The detailed molecular mechanisms of miR-204-5p remain to be verified.