Ma Weiping, Yue Yachao, Dong Bing, Wei Lei, Tian Liying
Department of Gastroenterology, Handan Central Hospital, Handan, Hebei 056000, P.R. China.
Department of Cardiovascular Surgery, Shanxi Provincial People's Hospital, Taiyuan, Shangxi 030032, P.R. China.
Oncol Lett. 2024 Aug 5;28(4):476. doi: 10.3892/ol.2024.14609. eCollection 2024 Oct.
Treatment modalities involving an immune-checkpoint-inhibitor (ICI) have emerged as therapeutic options in advanced hepatocellular carcinoma (HCC). Nonetheless, auxiliary biomarkers are required to evaluate their efficacy. The present study aimed to assess the potential of blood mucosa-associated lymphoid tissue 1 (MALT1) in reflecting clinical response and prognosis in patients with advanced HCC who received ICI therapy. Peripheral blood was collected from 51 patients with advanced HCC who were about to receive ICI or ICI-based treatment. Blood MALT1 levels were determined using reverse transcription-quantitative PCR, and the blood MALT1 levels in 50 healthy controls (HCs) were also assessed. Besides, the treatment response and survival data were collected. The Wilcoxon rank-sum test was used for comparison analysis and the Spearman's rank correlation coefficient test was used for correlation analysis. The prognostic value of MALT1 was determined by Kaplan-Meier curve analysis with the log-rank test. Univariate and multivariate Cox regression models were used to identify factors associated with progression-free survival (PFS) and overall survival (OS). The results demonstrated that blood MALT1 levels were significantly increased in patients with advanced HCC compared with that in HCs (P<0.001). Blood MALT1 levels were increased in patients with portal vein invasion (vs. without portal vein invasion; P=0.010), extrahepatic disease (vs. without extrahepatic disease; P=0.026) and α-fetoprotein (AFP) ≥200 ng/ml (vs. AFP <200 ng/ml; P=0.040). After 4 cycles of ICI therapy, the objective response rate (ORR) and disease control rate (DCR) was 29.4 and 68.6%, respectively. Blood MALT1 levels were also significantly and negatively associated with the ORR (P=0.043) and DCR (P=0.004). Furthermore, PFS and OS were shortened in patients with high blood MALT1 levels (cut-off by the median) compared to those with low blood MALT1 levels. After adjusting using multivariate Cox regression models, high blood MALT1 levels were demonstrated to be a significant independent risk factor for shortened PFS [hazard ratio (HR)=2.419; P=0.009] and OS (HR=2.706, P=0.018) in patients with advanced HCC who received ICI therapy. In summary, blood MALT1 levels serve as a potential biomarker to reflect treatment response and survival in patients with advanced HCC who receive ICI therapy.
涉及免疫检查点抑制剂（ICI）的治疗方式已成为晚期肝细胞癌（HCC）的治疗选择。尽管如此，仍需要辅助生物标志物来评估其疗效。本研究旨在评估血液黏膜相关淋巴组织1（MALT1）在接受ICI治疗的晚期HCC患者中反映临床反应和预后的潜力。收集了51例即将接受ICI或基于ICI治疗的晚期HCC患者的外周血。使用逆转录定量PCR测定血液MALT1水平，并评估了50名健康对照（HC）的血液MALT1水平。此外，收集了治疗反应和生存数据。采用Wilcoxon秩和检验进行比较分析，采用Spearman秩相关系数检验进行相关性分析。通过Kaplan-Meier曲线分析和对数秩检验确定MALT1的预后价值。使用单因素和多因素Cox回归模型来确定与无进展生存期（PFS）和总生存期（OS）相关的因素。结果表明，与HC相比，晚期HCC患者的血液MALT1水平显著升高（P<0.001）。门静脉侵犯患者（与无门静脉侵犯患者相比；P=0.010）、肝外疾病患者（与无肝外疾病患者相比；P=0.026）和甲胎蛋白（AFP）≥200 ng/ml患者（与AFP<200 ng/ml患者相比；P=0.040）的血液MALT1水平升高。在4个周期的ICI治疗后，客观缓解率（ORR）和疾病控制率（DCR）分别为29.4%和68.6%。血液MALT1水平也与ORR（P=0.043）和DCR（P=0.004）显著负相关。此外，与血液MALT1水平低的患者相比，血液MALT1水平高的患者（以中位数为界）的PFS和OS缩短。在使用多因素Cox回归模型进行调整后，血液MALT1水平高被证明是接受ICI治疗的晚期HCC患者PFS缩短[风险比（HR）=2.419；P=0.009]和OS缩短（HR=2.706，P=0.018）的显著独立危险因素。总之，血液MALT1水平可作为反映接受ICI治疗的晚期HCC患者治疗反应和生存情况的潜在生物标志物。
