PMID- 33217867
OWN - NLM
STAT- MEDLINE
DCOM- 20201207
LR  - 20221005
IS  - 1536-5964 (Electronic)
IS  - 0025-7974 (Print)
IS  - 0025-7974 (Linking)
VI  - 99
IP  - 47
DP  - 2020 Nov 20
TI  - Bioinformatics analysis of multi-omics data identifying molecular biomarker 
      candidates and epigenetically regulatory targets associated with retinoblastoma.
PG  - e23314
LID - 10.1097/MD.0000000000023314 [doi]
LID - e23314
AB  - Retinoblastoma (RB) is the commonest malignant tumor of the infant retina. 
      Besides genetic changes, epigenetic events are also considered to implicate the 
      occurrence of RB. This study aimed to identify significantly altered 
      protein-coding genes, DNA methylation, microRNAs (miRNAs), long noncoding RNAs 
      (lncRNAs), and their molecular functions and pathways associated with RB, and 
      investigate the epigenetically regulatory mechanism of DNA methylation 
      modification and non-coding RNAs on key genes of RB via bioinformatics method.We 
      obtained multi-omics data on protein-coding genes, DNA methylation, miRNAs, and 
      lncRNAs from the Gene Expression Omnibus database. We identified differentially 
      expressed genes (DEGs) using the Limma package in R, discerned their biological 
      functions and pathways using enrichment analysis, and conducted the modular 
      analysis based on protein-protein interaction network to identify hub genes of 
      RB. Survival analyses based on The Cancer Genome Atlas clinical database were 
      performed to analyze prognostic values of key genes of RB. Subsequently, we 
      identified the differentially methylated genes, differentially expressed miRNAs 
      (DEMs) and lncRNAs (DELs), and intersected them with key genes to analyze 
      possible targets of the underlying epigenetic regulatory mechanisms. Finally, the 
      ceRNA network of lncRNAs-miRNAs-mRNAs was constructed using Cytoscape.A total of 
      193 DEGs, 74 differentially methylated-DEGs (DM-DEGs), 45 DEMs, 5 DELs were 
      identified. The molecular pathways of DEGs were enriched in cell cycle, p53 
      signaling pathway, and DNA replication. A total of 10 key genes were identified 
      and found significantly associated with poor survival outcome based on survival 
      analyses, including CDK1, BUB1, CCNB2, TOP2A, CCNB1, RRM2, KIF11, KIF20A, NDC80, 
      and TTK. We further found that hub genes MCM6 and KIF14 were differentially 
      methylated, key gene RRM2 was targeted by DEMs, and key genes TTK, RRM2, and CDK1 
      were indirectly regulated by DELs. Additionally, the ceRNA network with 222 
      regulatory associations was constructed to visualize the correlations between 
      lncRNAs-miRNAs-mRNAs.This study presents an integrated bioinformatics analysis of 
      genetic and epigenetic changes that may be associated with the development of RB. 
      Findings may yield many new insights into the molecular biomarker candidates and 
      epigenetically regulatory targets of RB.
FAU - Zeng, Yuyang
AU  - Zeng Y
AD  - Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei 
      Province, People's Republic of China.
FAU - He, Tao
AU  - He T
FAU - Liu, Juejun
AU  - Liu J
FAU - Li, Zongyuan
AU  - Li Z
FAU - Xie, Feijia
AU  - Xie F
FAU - Chen, Changzheng
AU  - Chen C
AUID- ORCID: 0000-0002-7281-552
FAU - Xing, Yiqiao
AU  - Xing Y
AUID- ORCID: 0000-0001-5534-1951
LA  - eng
PT  - Journal Article
PT  - Observational Study
PL  - United States
TA  - Medicine (Baltimore)
JT  - Medicine
JID - 2985248R
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Biomarkers, Tumor/*genetics
MH  - Computational Biology/*methods
MH  - DNA Methylation
MH  - Data Mining
MH  - Databases, Genetic
MH  - Epigenomics
MH  - Gene Expression Regulation, Neoplastic
MH  - Gene Regulatory Networks
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Protein Interaction Maps/genetics
MH  - RNA, Long Noncoding/genetics
MH  - RNA, Messenger/genetics
MH  - Retinal Neoplasms/*genetics
MH  - Retinoblastoma/*genetics
PMC - PMC7676602
COIS- The authors have no conflicts of interests to disclose.
EDAT- 2020/11/22 06:00
MHDA- 2020/12/15 06:00
PMCR- 2020/11/20
CRDT- 2020/11/21 01:00
PHST- 2020/11/21 01:00 [entrez]
PHST- 2020/11/22 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/11/20 00:00 [pmc-release]
AID - 00005792-202011200-00082 [pii]
AID - MD-D-20-03427 [pii]
AID - 10.1097/MD.0000000000023314 [doi]
PST - ppublish
SO  - Medicine (Baltimore). 2020 Nov 20;99(47):e23314. doi: 
      10.1097/MD.0000000000023314.