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
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Zhi-Hua Ye1, Dong-Yue Wen2, Xiao-Yong Cai3, Liang Liang3, Pei-Rong Wu1, Hui Qin1, Hong Yang2, Yun He2 and Gang Chen1
1Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
2Department of Ultrasonography, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
3Department of General Surgery, First Affiliated Hospital of Guangxi Medical University (West), Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
Gang Chen, email: [email protected]
Keywords: miR-204-5p, TCGA, prognostic, malignancies, bioinformatics
Received: January 04, 2017 Accepted: September 23, 2017 Published: October 23, 2017
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.
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