Identification of a novel mutation gene signature HAMP for cholangiocarcinoma through comprehensive TCGA and GEO data mining.
Int Immunopharmacol
; 99: 108039, 2021 Oct.
Article
in En
| MEDLINE
| ID: mdl-34426102
ABSTRACT
Cholangiocarcinoma (CHOL), the second most common malignant liver tumor, is clinically heterogeneous. In this study, we used gene expression profiles of CHOL obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases to identify novel mutation signatures in CHOL. Hepcidin antimicrobial peptide (HAMP) was identified as a novel diagnostic biomarker for CHOL using the intersection of mutation analysis and receiver operating characteristic (ROC) analysis. We then explored the expression signatures of HAMP in CHOL. HAMP-related differentially expressed genes (DEGs) were selected for the identification of hub genes related to HAMP and for prognostic prediction model analysis. Gene set enrichment analysis (GSEA) showed that the HAMP-related DEGs were mainly enriched for signaling pathways related to cholangiocarcinoma development. Through immunohistochemistry validation, clinical cohorts analysis, and TCGA analysis, we investigated the association between HAMP and clinical parameters and found that decreased HAMP expression was correlated with advanced pathological grade and poor prognosis. Besides, we estimated the immune infiltration level in CHOL and its relationship with HAMP expression. The proportion of tumor-infiltrating cells revealed that gamma delta T cells and monocytes were positively correlated with HAMP expression. Besides, HAMP was also correlated with chemokine, CCL16. This evidence suggested that HAMP might contribute to immune activation in the CHOL microenvironment. Therefore, HAMP may play a synergistic role with these immune cells and chemokines to inhibit CHOL development. HAMP serves as a valuable biomarker in CHOL and is closely correlated with its progression.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bile Duct Neoplasms
/
Cholangiocarcinoma
/
Hepcidins
/
Mutation
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Int Immunopharmacol
Year:
2021
Document type:
Article