Abstract
Gallbladder carcinoma (GBC), which has high invasion and metastasis risks, remains the most common biliary tract malignancy. Surgical resection for GBC is the only effective treatment, but most patients miss the opportunity for curative surgery because of a lack of timely diagnosis. The aim of this study was to identify and verify early candidate diagnostic and prognostic RNA methylation related genes for GBC via integrated transcriptome bioinformatics analysis. Lists of GBC-related genes and methylation-related genes were collected from public databases to screen differentially expressed genes (DEGs) by using the limma package and the RobustRankAggreg (RRA) package. The core genes were collected with batch effects corrected by the RRA algorithm through protein interaction network analysis, signaling pathway enrichment analysis and gene ranking. Four modules obtained from four public microarray datasets were found to be related to GBC, and FGA, F2, HAO1, CFH, PIPOX, ITIH4, GNMT, MAT1A, MTHFD1, HPX, CTH, EPHX2, HSD17B6, AKR1C4, CFHR3, ENNP1, and NAT2 were revealed to be potential hub genes involved in methylation-related pathways and bile metabolism-related pathways. Among these, FGA, CFH, F2, HPX, and PIPOX were predicted to be methylated genes in GBC, but POPIX had no modification sites for RNA methylation. Furthermore, survival analysis of TCGA (the Cancer Genome Atlas) database showed that six genes among the hub genes, FGA, CFH, ENPP1, CFHR3, ITIH4, and NAT2, were highly expressed and significantly correlated with worse prognosis. Gene correlation analysis revealed that the FGA was positively correlated with the ENPP1, NAT2, and CFHR3, while CFH was positively correlated with the NAT2, CFHR3, and FGA. In addition, the results of immunohistochemistry (IHC) showed that the expressions of FGA, F2, CFH, PIPOX, ITIH4, GNMT, MAT1A, MTHFD1, HPX, CFHR3, NAT2, and ENPP1 were higher in GBC tissues than that in control tissues. In conclusion, two genes, FGA and CFH, were identified as RNA methylation-related genes also involved in bile metabolism in GBC, which may be novel biomarkers to early diagnose and evaluate prognosis for GBC.
Highlights
Gallbladder carcinoma (GBC), which originates from the epithelia of bile ducts and the gallbladder, is the most common malignancy of the biliary tract and has a high possibility of metastasis [1]
The results demonstrated that highly expressed FGA, Complement factor H (CFH), ENPP1, CFHR3, ITIH4, and NAT2 were associated with poor prognosis
FGA and CFH were identified as RNA methylation-related biomarkers in GBC, which may be novel biomarkers to early diagnose and evaluate prognosis for GBC
Summary
Gallbladder carcinoma (GBC), which originates from the epithelia of bile ducts and the gallbladder, is the most common malignancy of the biliary tract and has a high possibility of metastasis [1]. RNA methylation has been increasingly utilized to detect and predict the occurrence of Abbreviation: GBC, gallbladder carcinoma; DEGs, differentially expressed genes; RRA, RobustRankAggreg; PPI, protein-protein interaction; IHC, immunohistochemistry; TCGA, the Cancer Genome Atlas; GEO, gene expression omnibus; NCBI, national coalition building institute; KEGG, Kyoto encyclopedia of genes and genomes; EBI, European bioinformatics institute; limma, the linear models for microarray data; GO, gene ontology; FDR, false discovery rate; CHOL, cholangio carcinoma; SNP, single nucleotide polymorphisms; OS, overall survival; HR, hazard ratio; TISCH, the Tumor Immune Single-cell Hub database; FGA, fibrinogen alpha chain; F2, coagulation factor II; HAO1, the enzyme hydroxyacid oxidase 1; CFH, complement factor H; PIPOX, pipecolic acid and sarcosine oxidase; ITIH4, inter-alpha-trypsin inhibitor heavy chain 4; GNMT, glycine N-methyltransferase; MAT1A, methionine adenosyl transferase 1A; MTHFD1, methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1; HPX, hemagglutinin; CTH, cystathionine gamma-Lyase; EPHX2, epoxide hydrolase 2; HSD17B6, hydroxysteroid 17-Beta Dehydrogenase 6; AKR1C4, Aldo-Keto reductase family 1 member C4; CFHR3, complement factor H related 3; ENNP1, ectonucleotide pyrophosphatase/phosphodiesterase 1; NAT2, N-acetyltransferase 2; NSUN2, NOP2/Sun domain family member 2
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
