Identification and evaluation of plasma exosome RNA biomarkers for non-invasive diagnosis of hepatocellular carcinoma using RNA-seq.

Autor: Huang H; Infectious Disease Department, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China., Zhang M; BamRock Research Department, Suzhou BamRock Biotechnology Ltd., Suzhou, Jiangsu Province, China., Lu H; Infectious Disease Department, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China., Chen Y; Infectious Disease Department, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China., Sun W; Ulink College of Shanghai, Shanghai, China., Zhu J; Infectious Disease Department, The Fourth Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China. zhujinghan@139.com., Chen Z; Infectious Disease Department, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China. chenzt@suda.edu.cn.; MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Key Laboratory of Pathogen Bioscience and Anti-infective Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China. chenzt@suda.edu.cn.; Infectious Disease Department, The Fourth Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China. chenzt@suda.edu.cn.
Jazyk: angličtina
Zdroj: BMC cancer [BMC Cancer] 2024 Dec 18; Vol. 24 (1), pp. 1552. Date of Electronic Publication: 2024 Dec 18.
DOI: 10.1186/s12885-024-13332-0
Abstrakt: Background: Non-invasive diagnostic methods, including medical imaging techniques and blood biomarkers such as alpha-fetoprotein (AFP), have been crucial in detecting hepatocellular carcinoma (HCC). However, imaging techniques are only effective for tumor size larger than 2 cm. AFP measurement remains unsatisfactory due to high rate of misdiagnosis and underdiagnosis. Therefore, new reliable biomarkers and better non-invasive diagnostic approach are necessary for HCC identification.
Methods: The differentially expressed genes were identified using multiple public RNA-seq data of liver tissues from healthy individuals and HCC patients including peritumoral and tumor tissues. The hub genes for HCC diagnosis were identified combining pathway enrichment analysis and protein-protein interaction network analysis. The performance of hub genes for non-invasive HCC diagnosis was analyzed in plasma of healthy individuals, HBV infected patients, and HCC patients based on exosomal RNA-seq data. A multi-layer perceptron (MLP) model based on exosomal hub genes was developed for non-invasive HCC diagnosis.
Results: Through differential gene expression and pathway enrichment analysis on multiple public RNA-seq datasets, we first identified 30 dysregulated genes in HCC tissues. Protein-protein interaction analysis further narrowed down this list to 10 key genes: BRCA2, CDK1, MCM4, PLK1, DNA2, BLM, PCNA, POLD1, BRCA1 and FEN1. By further evaluation using additional public HCC tissue datasets, POLD1 and MCM4 were excluded from consideration as potential biomarkers due to their suboptimal performance. Notably, CDK1, FEN1, and PCNA gene were found to be significantly elevated in the plasma exosomes of HCC patients compared to non-HCC individuals, including those with HBV-infected hepatitis and healthy controls. The MLP model, based on three biomarkers, showed an area under the curve (AUC) of 0.85 and 0.84 in training and test dataset respectively, after adjusting for the covariates sex and age.
Conclusion: We identified three key genes, CDK1, FEN1, and PCNA, as exosomal biomarkers for non-invasive diagnosis of HCC. The MLP model utilizing three biomarkers showed good differentiation between non-HCC individuals and HCC patients, which exhibits promising potential as a non-invasive diagnostic tool for detecting HCC. Additional validation with a larger sample size is essential to thoroughly assess the reliability of the biomarkers and the model's performance.
Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the ethic committee of the First Affiliated Hospital of Soochow University (SZFAT-2022-310) and conformed to the principles of the Helsinki Declaration. Patient data was anonymized and confidentiality was maintained throughout the study. All the participants wrote informed content. Consent for publication: Not applicable. Clinical trial number: Not applicable. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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