Cholangiocarcinoma‑associated genes identified by integrative analysis of gene expression data

Abstract

Cholangiocarcinoma (CCA) is characterized by delayed diagnosis and poor survival rate. Research efforts have focused on novel diagnostic technologies for this type of cancer. Transcriptomic microarray technology is a useful research strategy for investigating the molecular properties of CCA. The objective of the present study was to identify candidate biomarkers with high potential for clinical application in CCA using a meta-analysis-based approach. Gene expression profiles of CCA were downloaded from the Gene Expression Omnibus database for integrated analysis. All differentially expressed genes (DEGs) were analyzed by Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Protein-protein interaction (PPI) networks were further constructed, hub proteins were identified and functional modules were extracted. Following integrated analysis of the seven eligible datasets (428 cases and 46 controls), a set of 1,080 DEGs was identified, including 710 upregulated and 370 downregulated genes. Functional enrichment analysis demonstrated that ‘chromosome organization’ was a significantly enriched GO term in the biological process category. ‘DNA replication’, ‘influenza A’, and ‘lysosome’ were the top three significantly enriched KEGG pathways. Furthermore, PPI network analysis indicated that the significant hub proteins were histone deacetylase 1, cullin-associated NEDD8-dissociated protein 1, ubiquitin D, early growth response protein 1 and glycogen synthase kinase 3β. The majority of these proteins are involved in CCA. These results provided a set of targets that may help researchers to clarify further the underlying mechanisms of CCA tumorigenesis.

Cancer-Associated Fibroblast-Derived IL-6 Determines Unfavorable Prognosis in Cholangiocarcinoma by Affecting Autophagy-Associated Chemoresponse

“…In the last few decades, gene profiling [ 12 , 13 , 14 , 15 ] and clinical histopathology [ 16 , 17 , 18 , 19 , 20 ] studies have greatly added to our knowledge of the genes and molecular pathways that are involved in the pathogenesis and progression, and define the prognosis, of CCA. The top genes that were found to be abnormally expressed in CCA, with a frequency ranging from 10% to >50 depending on the topographical location (intra or extrahepatic), the population studied, and the method include TP53 , KRAS , CDKN2/p16 INK4 , FGFR2 gene fusions, ERBB2 , IDH1 , and ARID1A [ 12 , 15 , 21 ].…”

FCN3 Is a Prognostic Biomarker Correlated with Immune Response in Liver Cancer

“…Due to discrete early clinical symptoms, lack of sensitive and speci c markers, and limited diagnostic methods patients are often treated during the middle and late stages of disease. The survival rate has not improved much in recent years [27,28]. Therefore, determining the key molecules causing liver cancer, exploring its internal mechanisms and nding potential therapeutic targets are future research directions.…”

Common features between neoplastic and preneoplastic lesions of the biliary tract and the pancreas

“…PDAC presents a significant inter-tumor and an intra-tumor heterogeneity and based on patterns of gene expression profiling, researchers classified PDAC into sub-groups with different molecular features such as (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine, that reflect a different clinical behavior with a potential for specific personalized treatment[134-136]. Genomic profiling studies have highlighted distinct subtypes also regarding CCA[137], some evidences demonstrated two main classes: the inflammation and the proliferation, with the latter being associated with worse outcome compared to the inflammation class[138]. In addition, in the past few years, an increasing attention has been paid on the potential role of noncoding RNAs (ncRNAs), classified according to their length into long (> 200 nucleotides) and small (18 to 200 nucleotides), for their involvement in cell proliferation, growth, tumor progression and drug resistance of several tumors[139,140].…”