Overexpression of Arginase-1 is an indicator of poor prognosis in patients with colorectal cancer
Overexpression of Arginase-1 is an indicator of poor prognosis in patients with colorectal cancer
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DOI：
10.1016/j.prp.2019.03.012
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发表时间：
2019-01-01
影响因子：
2.8
通讯作者：
Zhang, Yanqiao
中科院分区：
文献类型：
--
作者：
Ma, Zhigang;Lian, Jie;Zhang, Yanqiao
目的：精氨酸酶-1（Arg-1）代谢L-精氨酸生成L-鸟氨酸和尿素。它已被证明在各种恶性肿瘤中发挥作用。然而，Arg-1的表达和大肠癌（CRC）患者的临床病理特征之间的关系仍有待阐明。材料与方法：采用RT-qPCR（n = 24）和western blot（n = 17）方法检测24例新鲜大肠癌组织和17例癌旁组织中Arg-1 mRNA和蛋白的表达。Arg-1表达水平在石蜡包埋的CRC组织标本（n = 236）通过免疫组化测定。分析236例大肠癌组织中Arg-1表达与临床病理特征及临床预后的关系。Arg-1在结直肠癌组织中的表达水平显著高于相应的非癌组织，并且Arg-1的高表达与III-IV期肿瘤显著相关淋巴结转移（P = 0.019）和血浆白蛋白浓度< 35 g/l（P = 0.022）。Kaplan-Meier分析显示Arg-1过表达与所有病例的总生存期（OS）（P < 0.001）和无病生存期（DFS）（P < 0.001）相关。进一步分析显示，Arg-1高表达的患者在晚期（III + IV）的OS和DFS显著缩短（OS P = 0.032，DFS P = 0.012），但在早期（I + II）的OS和DFS没有显著缩短（OS P = 0.194，DFS P = 0.065）。多因素分析显示Arg-1过表达是影响结直肠癌患者OS（P = 0.002）和DFS（P < 0.001）的独立预后因素。
Aim: Arginase-1 (Arg-1) metabolizes L-arginine to L-omithine and urea. It has been documented to have a role in various malignancies. However, the relationship between Arg-1 expression and clinicopathological characteristics of colorectal cancer (CRC) patients remains to be elucidated. The present study aimed to analyze the expression and prognostic value of Arg-1 in patients with CRC.Material and methods: The mRNA and protein expressions of Arg-1 in fresh colorectal cancer tissue specimens and the corresponding noncancerous tissue specimens were examined by RT-qPCR (n = 24) and western blot analysis (n = 17). Arg-1 expression levels were determined in paraffin-embedded CRC tissue specimens (n = 236) by immunohistochemistry. The associations of Arg-1 expression and clinicopathological features and clinical prognosis in 236 CRC patients were analyzed.Results: The expression levels of Arg-1 were significantly higher in the CRC tissues compared with the matched noncancerous tissues, and elevated Arg-1 expression was remarkably associated with stage III-IV tumors (P = 0.007), lymph node metastasis (P = 0.019) and a plasma albumin concentration < 35 g/1 (P = 0.022). Kaplan-Meier analysis indicated that Arg-1 overexpression was associated with adverse prognoses for overall survival (OS) (P < 0.001) and disease-free survival (DFS) (P < 0.001) in all cases. Further analysis revealed that the patients with high Arg-1 expression had significantly shorter OS and DFS at the advanced stages (III + IV) (P = 0.032 for OS, and P = 0.012 for DFS) but not at the early stages (I + II) (P = 0.194 for OS, and P = 0.065 for DFS). Multivariate analysis revealed that Arg-1 overexpression was an independent prognostic factor for OS (P = 0.002) and DFS (P < 0.001) in patients with CRC.Conclusion: The data indicated that Arg-1 overexpression in CRC may be a marker that can discriminate subgroups of patients with a poor prognosis.