Bibliographic Details
Title: |
Multi-omics integration analysis of the amino-acid metabolism-related genes identifies putatively causal variants of ACCS associated with hepatitis B virus-related hepatocellular carcinoma survival |
Authors: |
Xiaoxia Wei, Xiaobing Yang, Shuangdi Duan, Qiuling Lin, Moqin Qiu, Qiuping Wen, Qiuyan Mo, Zihan Zhou, Yanji Jiang, Peiqin Chen, Xiumei Liang, Ji Cao, Qian Guo, Hongping Yu, Yingchun Liu |
Source: |
BMC Cancer, Vol 25, Iss 1, Pp 1-13 (2025) |
Publisher Information: |
BMC, 2025. |
Publication Year: |
2025 |
Collection: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
Subject Terms: |
Hepatocellular carcinoma, Amino acid metabolism, Single-nucleotide polymorphism, Overall survival, Integrative omics, Mendelian randomization, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
More Details: |
Abstract Background Amino acid metabolism (AAM) reprogramming plays a crucial role in hepatocellular carcinoma (HCC), but its genetic pathophysiology was not fully elucidated. Therefore, we employed a summary data-based Mendelian randomization (SMR) approach to identify putative causal effects of the AAM-related genes on hepatitis B virus (HBV)-HCC survival via integrating multi-omics data. Methods Multivariate Cox proportional hazards regression models were used to evaluate associations between genetic variants of AAM-related genes and overall survival (OS) of HBV-HCC patients (n = 866). Next, we developed a pathway-specific genetic risk score (GRS) comprising variants in the AAM pathway. Subsequently, putative causal SNPs were prioritized using SMR by integrating HBV-HCC OS data with expression quantitative trait loci (eQTLs) and DNA methylation QTLs (mQTLs) from the blood, as well a eQTLs of liver tissues. Results We identified 23 independent variants associated with HBV-HCC OS, and the pathway-specific GRS derived from the identified variants was a significant predictor of HBV-HCC OS. The addition of the GRS significantly improved the predictive performance of the 5-year survival model (AUC increased from 72.04% to 84.67%, P |
Document Type: |
article |
File Description: |
electronic resource |
Language: |
English |
ISSN: |
1471-2407 |
Relation: |
https://doaj.org/toc/1471-2407 |
DOI: |
10.1186/s12885-025-13604-3 |
Access URL: |
https://doaj.org/article/7cafbac6a54740a1b046adb487222cbf |
Accession Number: |
edsdoj.7cafbac6a54740a1b046adb487222cbf |
Database: |
Directory of Open Access Journals |
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