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©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
Combination of squamous cell carcinoma antigen immunocomplex and alpha-fetoprotein in mid- and long-term prediction of hepatocellular carcinoma among cirrhotic patients
Antonio Gil-Gómez, Ángela Rojas, Chang-Hai Liu, Rocio Gallego-Duran, Rocio Muñoz-Hernandez, Giorgio Fassina, Patrizia Pontisso, Javier Ampuero, Manuel Romero-Gómez
Antonio Gil-Gómez, Ángela Rojas, Rocio Gallego-Duran, Rocio Muñoz-Hernandez, Javier Ampuero, Manuel Romero-Gómez, SeLiver Group, Institute of Biomedicine of Seville, Seville 41013, Spain
Antonio Gil-Gómez, Ángela Rojas, Rocio Gallego-Duran, Rocio Muñoz-Hernandez, Javier Ampuero, Manuel Romero-Gómez, CIBERehd, Instituto de Salud Carlos III, Madrid 28029, Spain
Antonio Gil-Gómez, Mucosal Immunity Lab, IRCCS Humanitas Research Hospital, Milan 20089, Italy
Chang-Hai Liu, Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610017, Sichuan Province, China
Chang-Hai Liu, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Chengdu 610017, Sichuan Province, China
Giorgio Fassina, Life Biotechnology, Padua University, Venice 30175, Italy
Patrizia Pontisso, Department of Clinical and Experimental Medicine, University of Padova, Padova 35123, Italy
Javier Ampuero, Manuel Romero-Gómez, UCM Digestive Diseases, Virgen del Rocío University Hospital, Seville 41014, Spain
Author contributions: Gil-Gómez A led the formal analysis and writing-original draft; Rojas A equally contributed to the data curation and supported the formal analysis; Liu CH supported formal analysis and writing-original draft; Gallego-Duran R equally contributed to data curation, and led the resources; Muñoz-Hernandez R supported the data curation and validation; Fassina G and Pontisso P equally contributed to the validation; Ampuero J supported the conceptualization, led the supervision, and equally contributed to the writing-review and editing; Romero-Gómez M led the conceptualization, and equally contributed to the writing-review and editing.
Supported by Sara Borrell postdoctoral fellowships from Instituto de Salud Carlos III to support Ángela Rojas postdoctoral contract; Consejería de Salud y Familias, Junta de Andalucía supporting Antonio Gil-Gómez contract; PI19/01404 Grant from Spanish Ministry of Economy, Innovation and Competition, the Instituto de Salud Carlos III; PI19/00589/Spanish Ministry of Economy, Innovation and Competition, the Instituto de Salud Carlos III; and the Xeptagen, Italy, provided the ELISA kits for the measurements of SCCA-IgM. None of the founders had a role in the design, writing or interpretation of the study.
Institutional review board statement: Human samples were collected after obtaining a signed informed consent as approved by the Ethical Committee both hospitals (C330020).
Informed consent statement: Human samples were collected after obtaining a signed informed consent.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: The data presented in this study are available on request from the corresponding author. The data are not publicly available due to privacy reasons.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Manuel Romero-Gómez, MD, Full Professor, SeLiver Group, Institute of Biomedicine of Seville, Avda. Manuel Siurot sn, Seville 41013, Spain.
mromerogomez@us.es
Received: April 22, 2021
Peer-review started: April 22, 2021
First decision: June 13, 2021
Revised: June 27, 2021
Accepted: December 8, 2021
Article in press: December 8, 2021
Published online: December 28, 2021
Processing time: 245 Days and 22.8 Hours
BACKGROUND
The combination of alpha-fetoprotein (AFP) and squamous cell carcinoma antigen immunocomplex (SCCA-IgM) have been proposed for its use in the screening of hepatocellular carcinoma (HCC). Current screening programs for all cirrhotic patients are controversial and a personalized screening is an unmet need in the precision medicine era.
AIM
To determine the role of the combination of SCCA-IgM and AFP in predicting mid- and long-term appearance of HCC.
METHODS
Two-hundred and three cirrhotic patients (Child A 74.9%, B 21.2%, C 3.9%) were followed-up prospectively every six months to screen HCC by ultrasound and AFP according to European Association for the Study of the Liver guidelines. The estimation cohort was recruited in Italy (30.5%; 62/203) and validation cohort from Spain (69.5%; 141/203). Patients underwent to evaluate SCCA-IgM by enzyme-linked immunosorbent assay (Hepa-IC, Xeptagen, Italy) and AFP levels at baseline. Patients were followed-up for 60 mo, being censored at the time of the appearance of HCC.
RESULTS
There were 10.8% and 23.1% of HCC development at two- and five-years follow-up. Patients with HCC showed higher levels of SCCA-IgM than those without it (425.72 ± 568.33 AU/mL vs 195.93 ± 188.40 AU/mL, P = 0.009) during the five-year follow-up. In multivariate analysis, after adjusting by age, sex, aspartate transaminase and Child-Pugh, the following factors were independently associated with HCC: SCCA-IgM [Hazard ratio (HR) = 1.001, 95%CI: 1.000-1.002; P = 0.003], AFP (HR = 1.028, 95%CI: 1.009-1.046; P = 0.003) and creatinine (HR = 1.564 95%CI: 1.151-2.124; P = 0.004). The log-rank test of the combination resulted in 7.488 (P = 0.024) in estimation cohort and 11.061 (P = 0.004) in the validation cohort, and a 100% of correctly classified rate identifying a low-risk group in both cohorts in the two-year follow-up.
CONCLUSION
We have constructed a predictive model based on the combination of SCCA-IgM and AFP that provides a new HCC screening method, which could be followed by tailored HCC surveillance for individual patients, especially for those cirrhotic patients belonging to the subgroup identified as low-risk of HCC development.
Core Tip: Current screening programs of hepatocellular carcinoma (HCC) for all cirrhotic patients are controversial and a personalized strategy is an unmet need in the precision medicine era. By studying circulating biomarkers in two-hundred and three cirrhotic patients followed-up for 60 mo, we found that the combination of circulating alpha-fetoprotein and squamous cell carcinoma antigen immunocomplex resulted in a 100% of correctly classified rate identifying a low-risk group of HCC at two years of follow-up in two different cohorts. This predictive model provides a new screening method, which could be followed by tailored HCC surveillance for individual patients.
