High stromal nicotinamide N-methyltransferase (NNMT) indicates poor prognosis in colorectal cancer
High stromal nicotinamide N-methyltransferase (NNMT) indicates poor prognosis in colorectal cancer
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高基质烟酰胺 N-甲基转移酶 (NNMT) 表明结直肠癌预后不良
DOI：
10.1002/cam4.2890
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发表时间：
2020-01-27
期刊：
影响因子：
4
通讯作者：
Song, Chunhua
中科院分区：
文献类型：
--
作者：
Song, Mengmeng;Li, Ye;Song, Chunhua
目的烟酰胺N-甲基转移酶（NNMT）具有良好的生物化学活性和表观遗传学调节作用，是肿瘤的主要代谢调节因子。本研究的目的是探讨间质NNMT表达在结直肠癌（CRC）中的意义。方法采用免疫组织化学方法检测1088例原发性结直肠癌、转移性结直肠癌及其癌旁组织中NNMT的表达。采用Kaplan-Meier曲线和考克斯模型分析967例I ~ III期结直肠癌患者间质NNMT表达与生存结局的关系。结果NNMT的表达主要来源于间质区，在结直肠癌中也有表达。高基质NNMT患者（IHC评分>= 106）的生存率低于低基质NNMT患者。在多重考克斯分析中，间质NNMT高表达仍然是CRC无病生存的独立风险因素，风险比（HR）为1.415（95%置信区间[CI]，1.015-1.972），疾病特异性生存的风险比（HR）为5.004（95% CI，2.301-10.883）。此外，CRC中高基质NNMT表达也表明早期CRC（I期和II期）患者和接受化疗患者的生存结局较差。结论NNMT主要定位于结直肠癌间质区。间质NNMT高表达预示术后预后不良。
Purpose Nicotinamide n-methyltransferase (NNMT) has good biochemical activity and epigenetic regulation, and has been reported as a major metabolic regulator of cancer. The goal of this study was to investigate the significance of stromal NNMT expression in colorectal cancer (CRC). Patients and methods Stromal expression of NNMT in primary CRC, metastasis CRC, and their non-cancerous tissues from 1088 CRC patients was examined by immunohistochemistry. The associations between stromal NNMT expression and survival outcomes in 967 patients with stage I-III CRC were further evaluated with Kaplan-Meier curve and Cox model analyses. Results NNMT expression was mainly sourced from stromal compartments and also elevated in CRC. Patients with high stromal NNMT (IHC-score >= 106) have a worse survival than those patients with low stromal NNMT. In multiple Cox analyses, high expression of stromal NNMT remained as an independent risk factor in CRC for disease-free survival with a hazard ratio (HR) of 1.415 (95% confidence interval [CI], 1.015-1.972) and disease-specific survival with a HR of 5.004 (95% CI, 2.301-10.883). In addition, high stromal NNMT expression in CRC also indicates the poor survival outcomes in patients with early stage CRC (stage I and II) and in patients who undergo chemotherapy. Conclusion NNMT is mainly located in CRC stromal compartment. High stromal NNMT expression predicts an unfavorable postoperative prognosis.