Rs9679162 genotype predicts prognosis of real-world advanced hepatocellular carcinoma treated by sorafenib.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Applied Bio Materials Pub Date : 2023-01-01 DOI:10.3233/CBM-220042

Chih-Lang Lin, Rong-Nan Chien, Li-Wei Chen, Yu-De Chu, Chau-Ting Yeh

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引用次数: 0

Abstract

Background: Sorafenib and lenvatinib are tyrosine kinase inhibitors widely used in the targeted therapy to treat advanced hepatocellular carcinoma (aHCC). The GALNT14-rs9679162 genotype is a predictor of therapeutic outcome in multiple gastrointestinal cancers.

Objective: To investigate the predictive role of the GALNT14-rs9679162 genotype in aHCC treated with sorafenib or lenvatinib.

Methods: Totally 350 real-world patients with aHCC received sorafenib or lenvatinib were enrolled for GALNT14-rs9679162 genotyping and outcome analysis. Kaplan-Meier and Cox regression analysis were conducted to evaluate therapeutic outcomes. Cell-based assays were performed to determine the underlying mechanism.

Results: Kaplan-Meier and Cox regression analysis showed that the "GG" genotype was not associated with overall survival (OS) when all patients were included. However, it was associated with shorter OS in specific clinical subgroups, including anti-hepatitis C virus antibody-positive (n= 108; P= 0.005) and hepatitis B surface antigen-negative (n= 117; P= 0.002) patients. Intriguingly, hepatitis B virus X protein trans-suppressed the GALNT14 promoter, thereby reducing the elevated expression of GALNT14 in hepatoma cells, which partially contributed to the inability of the GALNT14-rs9679162 genotypes to predict the outcome of hepatitis B-related HCC. Finally, by analyzing the outcomes of 52 patients with aHCC treated with lenvatinib, patients with the "GG" genotype were associated with a favorable/shorter time-to-response (P= 0.013).

Conclusions: The GALNT14-rs9679162 "GG" genotype predicted shorter OS in patients with HBsAg-negative aHCC treated with sorafenib, but predicted a favorable response in all patients with aHCC treated with lenvatinib.

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Rs9679162基因型预测索拉非尼治疗晚期肝癌的预后

背景:索拉非尼和lenvatinib是酪氨酸激酶抑制剂，广泛用于晚期肝细胞癌(aHCC)的靶向治疗。GALNT14-rs9679162基因型是多种胃肠道癌症治疗结果的预测因子。目的:探讨GALNT14-rs9679162基因型在索拉非尼或lenvatinib治疗aHCC中的预测作用。方法:对350例接受索拉非尼或lenvatinib治疗的aHCC患者进行GALNT14-rs9679162基因分型和结果分析。Kaplan-Meier和Cox回归分析评价治疗结果。以细胞为基础的实验确定潜在的机制。结果:Kaplan-Meier和Cox回归分析显示，当纳入所有患者时，“GG”基因型与总生存率(OS)无相关性。然而，在特定的临床亚组中，它与较短的生存期相关，包括抗丙型肝炎病毒抗体阳性(n= 108;P= 0.005)和乙型肝炎表面抗原阴性(n= 117;P= 0.002)。有趣的是，乙型肝炎病毒X蛋白反式抑制GALNT14启动子，从而降低了GALNT14在肝癌细胞中的高表达，这部分促成了GALNT14-rs9679162基因型无法预测乙型肝炎相关HCC的预后。最后，通过对52例lenvatinib治疗aHCC患者的结果分析，“GG”基因型患者具有较好的/较短的应答时间(P= 0.013)。结论:GALNT14-rs9679162“GG”基因型预测索拉非尼治疗的hbsag阴性aHCC患者的OS较短，但预测lenvatinib治疗的所有aHCC患者的OS较好。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464