Lin Q, Bai MJ, Wang HF, Wu XY, Huang MS, Li X. Aspirin-induced long-term tumor remission in hepatocellular carcinoma with adenomatous polyposis coli stop-gain mutation: A case report. World J Clin Cases 2021; 9(24): 7189-7195 [PMID: 34540977 DOI: 10.12998/wjcc.v9.i24.7189]
Corresponding Author of This Article
Xing Li, MD, Professor, Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China. lixing9@mail.sysu.edu.cn
Research Domain of This Article
Medicine, Research & Experimental
Article-Type of This Article
Case Report
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Qu Lin, Xiang-Yuan Wu, Xing Li, Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
Ming-Jun Bai, Hao-Fan Wang, Ming-Sheng Huang, Department of Intervention and Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
Author contributions: Lin Q and Huang MS recruited the patient and made clinical decisions; Bai MJ and Wang HF carried out the follow up; Li X, Wang HF and Bai MJ performed the image analysis; Li X performed the molecular analysis; Lin Q, Huang MS, Wu XY and Li X carried out the molecular pathway analysis; Li X wrote the manuscript; Huang MS is the co-corresponding author.
Supported byGuangzhou Science and Technology Project, No. 201904010461; and Major Talents Project of Guangdong Province, No. 2019TQ05Y266.
Informed consent statement: Informed written consent was obtained from the patient for publication of this report and any accompanying images.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xing Li, MD, Professor, Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China. lixing9@mail.sysu.edu.cn
Received: February 1, 2021 Peer-review started: February 1, 2021 First decision: March 7, 2021 Revised: April 6, 2021 Accepted: May 18, 2021 Article in press: May 18, 2021 Published online: August 26, 2021 Processing time: 203 Days and 11 Hours
Abstract
BACKGROUND
Targeted therapy based on pathway analysis of hepatitis B-related hepatocellular carcinoma (HCC) may be a promising remedy.
CASE SUMMARY
The present case involved an advanced hepatocellular carcinoma (HCC) patient who did not receive local regional therapy and was intolerant to sorafenib. Total RNA extracted from the patient’s tumor tissue was used to obtain the gene mutation profile. The c.3676A>T and c.4402A>T stop-gain mutations in adenomatous polyposis coli (APC) were the most prevalent (42.2% and 35.1%, respectively). MutationMapper analysis indicated that the functional domain of APC was lost in the two APC mutant genes. APC is a major suppressor of the Wnt signaling pathway. Thus, the Wnt pathway was exclusively activated due to APC dysfunction, as other elements of this pathway were not found to be mutated. Aspirin has been reported to suppress the Wnt pathway by inducing β-catenin phosphorylation through the activation of glycogen synthase kinase 3 beta via cyclooxygenase-2 pathway inhibition. Therefore, aspirin was administered to the patient, which achieved four years of disease control.
CONCLUSION
Exclusive mutations of APC of all the Wnt pathway elements could be a therapeutic target in HCC, with aspirin as an effective treatment option.
Core Tip: Hepatocellular carcinoma (HCC) is a highly heterogeneous disease. Due to the differences in etiology and ethnicities, the driving genes in HCC are likely to be different globally. Adenomatous polyposis coli (APC) mutations are critical in a fraction of HCC patients, as APC mutations might trigger HCC by activating the Wnt pathway. The effects of this mutation could be consistently suppressed by aspirin. Thus, APC mutation-triggered HCC might be a new subgroup of chronic hepatitis B virus infection-related HCC. Wnt pathway inhibition could be an effective remedy for this subgroup of patients.
