Lin Qu, Bai Ming-Jun, Wang Hao-Fan, Wu Xiang-Yuan, Huang Ming-Sheng, Li Xing
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.
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.
World J Clin Cases. 2021 Aug 26;9(24):7189-7195. doi: 10.12998/wjcc.v9.i24.7189.
Targeted therapy based on pathway analysis of hepatitis B-related hepatocellular carcinoma (HCC) may be a promising remedy.
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 cyclooxygenase-2 pathway inhibition. Therefore, aspirin was administered to the patient, which achieved four years of disease control.
Exclusive mutations of APC of all the Wnt pathway elements could be a therapeutic target in HCC, with aspirin as an effective treatment option.
基于乙肝相关肝细胞癌（HCC）通路分析的靶向治疗可能是一种有前景的治疗方法。
本病例为一名晚期肝细胞癌（HCC）患者，未接受局部区域治疗且对索拉非尼不耐受。从患者肿瘤组织中提取的总RNA用于获取基因突变谱。腺瘤性息肉病 coli（APC）中的c.3676A>T和c.4402A>T 终止获得突变最为常见（分别为42.2%和35.1%）。MutationMapper分析表明，两个APC突变基因中APC的功能域缺失。APC是Wnt信号通路的主要抑制因子。因此，由于APC功能障碍，Wnt通路被单独激活，因为该通路的其他元件未发现突变。据报道，阿司匹林通过激活糖原合酶激酶3β 环氧化酶-2途径抑制来诱导β-连环蛋白磷酸化，从而抑制Wnt通路。因此，给该患者使用了阿司匹林，实现了四年的疾病控制。
Wnt通路所有元件中APC的单独突变可能是HCC的治疗靶点，阿司匹林是一种有效的治疗选择。
