Noda Yu, Kawaguchi Takumi, Korenaga Masaaki, Yoshio Sachiyo, Komukai Sho, Nakano Masahito, Niizeki Takashi, Koga Hironori, Kawaguchi Atsushi, Kanto Tatsuya, Torimura Takuji
Division of Gastroenterology, Kurume University School of Medicine, Kurume, Japan.
The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
Hepatol Res. 2019 Sep;49(9):1046-1053. doi: 10.1111/hepr.13350. Epub 2019 May 29.
We aimed to investigate the impact of interleukin (IL)-34 and YKL-40, regulators of hepatic fibrosis and tumor growth, on the prognosis of patients with non-viral hepatocellular carcinoma (HCC).
We enrolled 159 non-viral HCC patients (age, 70.8 ± 8.5 years; female/male, 43/116). Of these, 86 patients were alive and 73 patients had died at the censor time point. Serum IL-34 and YKL-40 levels were quantified by enzyme-linked immunosorbent assay. Patients were stratified by the median level of serum IL-34 to examine its effect on survival. Multivariate analysis and random forest analysis were used to evaluate the impact of IL-34 and YKL-40 on the prognosis of non-viral HCC patients.
Interleukin-34 (hazard ratio [HR] 1.30; 95% confidence interval [CI], 1.13-1.49; P ≤ 0.01), tumor size (HR 1.63; 95% CI, 1.37-1.94; P ≤ 0.01), and tumor number (HR 1.53; 95% CI, 1.25-1.87; P ≤ 0.01) were independent predictive factors for survival. Furthermore, the survival rates were significantly lower in the high IL-34 group than in the low IL-34 group (5-year survival rates, 34.7% vs. 59.8%, respectively; P < 0.05). In the random forest analysis for survival, IL-34 was the third-highest ranking factor, following tumor size and number. In a stratification analysis, serum α-fetoprotein level and Fibrosis-4 index were independent positive risk factors for high serum IL-34 level. YKL-40 was not associated with prognosis in either the multivariate or random forest analysis.
Interleukin-34 was an independent factor for survival of non-viral HCC patients. Interleukin-34 might be associated with prognosis through tumor and hepatic fibrosis factors.
我们旨在研究白细胞介素（IL）-34和YKL-40（肝纤维化和肿瘤生长的调节因子）对非病毒性肝细胞癌（HCC）患者预后的影响。
我们纳入了159例非病毒性HCC患者（年龄70.8±8.5岁；女性/男性，43/116）。其中，86例患者存活，73例患者在审查时间点死亡。采用酶联免疫吸附测定法定量血清IL-34和YKL-40水平。根据血清IL-34的中位数水平对患者进行分层，以检查其对生存的影响。采用多变量分析和随机森林分析来评估IL-34和YKL-40对非病毒性HCC患者预后的影响。
白细胞介素-34（风险比[HR]1.30；95%置信区间[CI]，1.13-1.49；P≤0.01）、肿瘤大小（HR 1.63；95%CI，1.37-1.94；P≤0.01）和肿瘤数量（HR 1.53；95%CI，1.25-1.87；P≤0.01）是生存的独立预测因素。此外，高IL-34组的生存率显著低于低IL-34组（5年生存率分别为34.7%和59.8%；P<0.05）。在生存的随机森林分析中，IL-34是排名第三的因素，仅次于肿瘤大小和数量。在分层分析中，血清甲胎蛋白水平和纤维化-4指数是血清IL-34水平升高的独立阳性危险因素。在多变量分析或随机森林分析中，YKL-40均与预后无关。
白细胞介素-34是非病毒性HCC患者生存的独立因素。白细胞介素-34可能通过肿瘤和肝纤维化因素与预后相关。
