Overexpression of Arginase-1 is an indicator of poor prognosis in patients with colorectal cancer |
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Authors: | Zhigang Ma Jie Lian Ming Yang Jiazi Wuyang Ci Zhao Wenhao Chen Chao Liu Qi Zhao Changjie Lou Jiguang Han Yanqiao Zhang |
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Institution: | 1. Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150040, PR China;2. Department of Colorectal Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, PR China;3. Department of Biotherapy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150040, PR China;4. Center of Oncology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, PR China;5. Peking University Sixth Hospital, Beijing, 100191, PR China;6. Department of Endoscopy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150040, PR China;7. Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150040, PR China |
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Abstract: | AimArginase-1 (Arg-1) metabolizes l-arginine to l-ornithine 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 methodsThe 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.ResultsThe 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/l (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.ConclusionThe data indicated that Arg-1 overexpression in CRC may be a marker that can discriminate subgroups of patients with a poor prognosis. |
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Keywords: | Corresponding author at: Department of Gastrointestinal Medical Oncology Harbin?Medical University Cancer Hospital 150 Haping Road Nangang Harbin Heilongjiang 150040 PR China Arginase-1 Colorectal cancer Immunohistochemistry Prognosis |
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