Decreased ARG1 expression as an adverse prognostic phenotype in non-alcoholic non-virus-related hepatocellular carcinoma
Decreased ARG1 expression as an adverse prognostic phenotype in non-alcoholic non-virus-related hepatocellular carcinoma
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DOI：
10.1007/s00428-022-03318-3
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发表时间：
2022-04
期刊：
影响因子：
3.5
通讯作者：
Y. Shigematsu;Gulanbar Amori;Hiroaki Kanda;Yukari Takahashi;Yutaka Takazawa;K. Takeuchi;K. Inamura
中科院分区：
文献类型：
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作者：
Y. Shigematsu;Gulanbar Amori;Hiroaki Kanda;Yukari Takahashi;Yutaka Takazawa;K. Takeuchi;K. Inamura
非酒精性非病毒相关性肝细胞癌（NANV-HCC）的发病率随着代谢紊乱患病率的增加而沿着增加。在这个子集中，很少有有用的生物标志物可用于缩小复发的高风险组。本研究旨在评估NANV-HCC中ARG 1（脱氢酶-1）降低的预后影响，ARG 1在病理学上被认为是反映肝细胞分化的标志物。此外，还评估了其与胆管/祖细胞标志物的关系，这些标志物的表达与不良预后相关。为了揭示NANV-HCC中ARG 1表达降低的临床病理学相关性，我们调查了99例接受根治性肝切除术的NANV-HCC患者。采用组织芯片进行免疫组织化学分析。共有21例NANV-HCC病例（21%; 21/99）显示ARG 1表达降低。ARG 1表达降低是DFS（风险比2.17; 95%置信区间1.15-4.09;p= 0.02）和OS（风险比4.09; 95%置信区间1.71-9.80;p= 0.002）不良的独立预后因素。此外，ARG 1表达降低与胆管/祖细胞标志物CK 19和CD 56的表达显著相关（p< 0.01）。作为肿瘤细胞的细胞学特征，ARG 1表达降低与无脂质细胞学形态显著相关（p= 0.045）。这些发现表明，ARG 1表达降低是NANV-HCC患者术后复发和预后不良的预测表型。ARG 1表达降低可能是NANV-HCC中胆管/祖细胞标志物表达的前体或重叠特征。
The incidence of non-alcoholic non-virus-related hepatocellular carcinoma (NANV-HCC) is increasing along with the growing prevalence of metabolic disorders. In this subset, few useful biomarkers are available to narrow down the high-risk group for recurrence. This study aimed to evaluate the prognostic impact of decreased ARG1 (arginase-1), which is pathologically known as a marker reflecting hepatocyte differentiation, in NANV-HCC. Besides, its relationship with biliary/progenitor cell markers, whose expressions are associated with poor prognosis, was also assessed. To reveal the clinicopathological association of decreased ARG1 expression in NANV-HCC, we investigated 99 patients who underwent curative-intent hepatectomy for NANV-HCC. Tissue microarrays were employed for immunohistochemical analysis. A total of 21 NANV-HCC cases (21%; 21/99) showed decreased ARG1 expression. Decreased ARG1 expression was an independent prognostic factor for both poor DFS (hazard ratio 2.17; 95% confidence interval 1.15–4.09;p= 0.02) and OS (hazard ratio 4.09; 95% confidence interval 1.71–9.80;p= 0.002). In addition, decreased ARG1 expression was significantly associated with expressions of biliary/progenitor cell markers, CK19 and CD56 (p< 0.01). As cytologic features of tumor cells, decreased ARG1 expression was significantly associated with lipid-less cytologic morphology (p= 0.045). These findings indicate that decreased ARG1 expression is a predictive phenotype of postoperative recurrence with poor prognosis in patients with NANV-HCC. Decreased ARG1 expression may be a precursor or overlapping feature with biliary/progenitor cell marker expressions in NANV-HCC.