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Application of the Multi-Omics Liquid Biopsy Method M2P-HCC in Early Liver Cancer Screening for High-Risk Individuals with Hepatitis B-Related Liver Cancer

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with low rates of early diagnosis and surgical resection. In recent years, with the rapid development of liquid biopsy technology, circulating tumor DNA (ctDNA) has emerged as a research hotspot in the f...

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Autores principales: Yu, Xian, Lei, Xuezhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10417463/
https://www.ncbi.nlm.nih.gov/pubmed/37568847
http://dx.doi.org/10.3390/diagnostics13152484
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author Yu, Xian
Lei, Xuezhong
author_facet Yu, Xian
Lei, Xuezhong
author_sort Yu, Xian
collection PubMed
description Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with low rates of early diagnosis and surgical resection. In recent years, with the rapid development of liquid biopsy technology, circulating tumor DNA (ctDNA) has emerged as a research hotspot in the field of precision medicine for liver cancer. Existing studies have demonstrated the suitability of ctDNA for combined detection with other liver cancer diagnostic markers, enabling a multi-index analysis. In recent years, a novel prediction model has been developed for early liver cancer screening based on ctDNA liquid biopsy, M2P-HCC (methylation, mutation, and protein-HCC), mainly incorporating methylation changes, gene mutations, and protein markers associated with liver cancer. Preliminary validation in the HCCscreenTM Investigational (HIT, ChiCTR1800020233) study, which focused on screening early liver cancer in communities with Hepatitis B surface antigen (HBsAg) positivity, yielded promising results with 100% sensitivity and 94% specificity. However, it remains uncertain whether M2P-HCC can be effectively applied in high-risk populations for Hepatitis B-associated liver cancer, warranting further research. Methods: Patients who were under long-term follow-up at the outpatient clinic of the Infectious Diseases Center of West China Hospital of Sichuan University from December 2020 to January 2023 were recruited in this prospective observational study and underwent the M2P-HCC test. The study population consisted of high-risk patients with Hepatitis B-related liver cancer who met the inclusion criteria. Patients with a history of previous malignancy, recent blood transfusion, autoimmune diseases, and human immunodeficiency virus (HIV) infection were excluded. Clinical data were collected at a baseline, and all patients underwent the M2P-HCC blood test. Based on the test results, they were categorized into positive, early-warning, and negative groups. Prospective cohort observation and regular follow-ups were performed for 6–8 months. Results: 313 patients met the inclusion criteria and were included in the study. After 6–8 months of follow-up, HCC occurred in 41(13.1%) participants. The M2P-HCC test demonstrated good predictive performance with an area under the curve (AUC) of 0.88 (95% CI: 0.81–0.95, p < 0.001) and a cutoff value of 83 points (sensitivity 82.9% and specificity 85.7%). In contrast, the combination of alpha-fetoprotein (AFP) and ultrasound (US) yielded an inferior predictive performance (AUC 0.76 (95% CI: 0.69–0.84, p < 0.001), sensitivity 58.5%, and specificity 94.1%). Multivariate analyses revealed that M2P-HCC was an independent predictor of increased risk of HCC (OR = 1.16 [1.09–1.22], p < 0.001). Conclusions: M2P-HCC liquid biopsy demonstrated good performance for early liver cancer screening in high-risk populations of Hepatitis B-related liver cancer, exhibiting better sensitivity than the combination of AFP and US.
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spelling pubmed-104174632023-08-12 Application of the Multi-Omics Liquid Biopsy Method M2P-HCC in Early Liver Cancer Screening for High-Risk Individuals with Hepatitis B-Related Liver Cancer Yu, Xian Lei, Xuezhong Diagnostics (Basel) Article Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with low rates of early diagnosis and surgical resection. In recent years, with the rapid development of liquid biopsy technology, circulating tumor DNA (ctDNA) has emerged as a research hotspot in the field of precision medicine for liver cancer. Existing studies have demonstrated the suitability of ctDNA for combined detection with other liver cancer diagnostic markers, enabling a multi-index analysis. In recent years, a novel prediction model has been developed for early liver cancer screening based on ctDNA liquid biopsy, M2P-HCC (methylation, mutation, and protein-HCC), mainly incorporating methylation changes, gene mutations, and protein markers associated with liver cancer. Preliminary validation in the HCCscreenTM Investigational (HIT, ChiCTR1800020233) study, which focused on screening early liver cancer in communities with Hepatitis B surface antigen (HBsAg) positivity, yielded promising results with 100% sensitivity and 94% specificity. However, it remains uncertain whether M2P-HCC can be effectively applied in high-risk populations for Hepatitis B-associated liver cancer, warranting further research. Methods: Patients who were under long-term follow-up at the outpatient clinic of the Infectious Diseases Center of West China Hospital of Sichuan University from December 2020 to January 2023 were recruited in this prospective observational study and underwent the M2P-HCC test. The study population consisted of high-risk patients with Hepatitis B-related liver cancer who met the inclusion criteria. Patients with a history of previous malignancy, recent blood transfusion, autoimmune diseases, and human immunodeficiency virus (HIV) infection were excluded. Clinical data were collected at a baseline, and all patients underwent the M2P-HCC blood test. Based on the test results, they were categorized into positive, early-warning, and negative groups. Prospective cohort observation and regular follow-ups were performed for 6–8 months. Results: 313 patients met the inclusion criteria and were included in the study. After 6–8 months of follow-up, HCC occurred in 41(13.1%) participants. The M2P-HCC test demonstrated good predictive performance with an area under the curve (AUC) of 0.88 (95% CI: 0.81–0.95, p < 0.001) and a cutoff value of 83 points (sensitivity 82.9% and specificity 85.7%). In contrast, the combination of alpha-fetoprotein (AFP) and ultrasound (US) yielded an inferior predictive performance (AUC 0.76 (95% CI: 0.69–0.84, p < 0.001), sensitivity 58.5%, and specificity 94.1%). Multivariate analyses revealed that M2P-HCC was an independent predictor of increased risk of HCC (OR = 1.16 [1.09–1.22], p < 0.001). Conclusions: M2P-HCC liquid biopsy demonstrated good performance for early liver cancer screening in high-risk populations of Hepatitis B-related liver cancer, exhibiting better sensitivity than the combination of AFP and US. MDPI 2023-07-26 /pmc/articles/PMC10417463/ /pubmed/37568847 http://dx.doi.org/10.3390/diagnostics13152484 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yu, Xian
Lei, Xuezhong
Application of the Multi-Omics Liquid Biopsy Method M2P-HCC in Early Liver Cancer Screening for High-Risk Individuals with Hepatitis B-Related Liver Cancer
title Application of the Multi-Omics Liquid Biopsy Method M2P-HCC in Early Liver Cancer Screening for High-Risk Individuals with Hepatitis B-Related Liver Cancer
title_full Application of the Multi-Omics Liquid Biopsy Method M2P-HCC in Early Liver Cancer Screening for High-Risk Individuals with Hepatitis B-Related Liver Cancer
title_fullStr Application of the Multi-Omics Liquid Biopsy Method M2P-HCC in Early Liver Cancer Screening for High-Risk Individuals with Hepatitis B-Related Liver Cancer
title_full_unstemmed Application of the Multi-Omics Liquid Biopsy Method M2P-HCC in Early Liver Cancer Screening for High-Risk Individuals with Hepatitis B-Related Liver Cancer
title_short Application of the Multi-Omics Liquid Biopsy Method M2P-HCC in Early Liver Cancer Screening for High-Risk Individuals with Hepatitis B-Related Liver Cancer
title_sort application of the multi-omics liquid biopsy method m2p-hcc in early liver cancer screening for high-risk individuals with hepatitis b-related liver cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10417463/
https://www.ncbi.nlm.nih.gov/pubmed/37568847
http://dx.doi.org/10.3390/diagnostics13152484
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