Correlations of the expression of silencing information regulatory factor 2-related enzyme-1 and colony-stimulating factor 1 receptors with clinical features and prognosis in patients with colon cancer
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摘要:目的
探讨沉默信息调节因子2相关酶1(SIRT1)和集落刺激因子1受体(CSF1R)表达与结肠癌患者临床特征及预后的关系。
方法收集148例结肠癌患者术中切除的结肠癌组织标本及癌旁组织标本。分析结肠癌患者的临床病理特征。采用免疫组织化学法检测SIRT1和CSF1R的表达; 采用Spearman相关分析法分析SIRT1与CSF1R的相关性; 采用Kaplan-Meier法分析SIRT1、CSF1R表达与患者预后的关系; 采用多因素Cox回归分析法分析结肠癌患者预后的影响因素。
结果与癌旁组织相比，结肠癌组织中SIRT1蛋白表达降低, CSF1R蛋白表达升高，差异有统计学意义(P < 0.05)。SIRT1与CSF1R蛋白表达与结肠癌患者的淋巴结转移、神经侵袭、浸润深度情况相关(P < 0.05)。SIRT1与CSF1R蛋白表达呈负相关(r=-0.536, P < 0.05)。SIRT1高表达结肠癌患者3年生存率高于SIRT1低表达患者，差异有统计学意义(P < 0.05)。CSF1R高表达结肠癌患者3年生存率低于CSF1R低表达患者，差异有统计学意义(P < 0.05)。淋巴结转移、浸润深度、神经侵袭、SIRT1、CSF1R是结肠癌患者预后的影响因素(P < 0.05)。
结论结肠癌患者癌组织中SIRT1表达显著下调, CSF1R表达显著上调，且与患者淋巴结转移、神经侵袭、浸润深度等临床病理特征密切相关，检测其水平对预测患者预后生存情况具有重要价值。
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关键词:
- 沉默信息调节因子2相关酶1 /
- 集落刺激因子1受体 /
- 结肠癌 /
- 临床病理特征 /
- 预后
Abstract:ObjectiveTo investigate the correlations of the expression of silent information regulator 2 homolog 1 (SIRT1) and colony-stimulating factor 1 receptor (CSF1R) with the clinical characteristics and prognosis of patients with colon cancer.
MethodsColon cancer tissue specimens and paracancer tissue specimens were collected from 148 patients with colon cancer. The clinical and pathological features of the patients were analyzed. Immunohistochemistry was used to detect the expression of SIRT1 and CSF1R; the Spearman's correlation analysis was employed to assess the correlation between SIRT1 and CSF1R; the Kaplan-Meier analysis was conducted to evaluate the associations of the expression of SIRT1 and CSF1R with patients' prognosis; the multivariate Cox regression analysis was performed to identify prognostic factors in colon cancer patients.
ResultsCompared with the adjacent tissues, the expression of SIRT1 protein in colon cancer tissues was significantly decreased, and the expression of CSF1R protein was significantly increased (P < 0.05). The expressions of SIRT1 and CSF1R protein were correlated with lymph node metastasis, nerve invasion and invasion depth in patients with colon cancer (P < 0.05). The protein expressions of SIRT1 and CSF1R were negatively correlated (r=-0.536, P < 0.05). The 3-year survival rate of patients with high SIRT1 expression was significantly higher than that of patients with low SIRT1 expression (P < 0.05). The 3-year survival rate of patients with high CSF1R expression was significantly lower than that of patients with low CSF1R expression (P < 0.05). The 3-year survival rate of patients with high SIRT1 expression was significantly higher than that of patients with low SIRT1 expression (P < 0.05).
ConclusionIn colon cancer, SIRT1 expression is significantly downregulated, whereas CSF1R expression is upregulated, and both are closely related to the clinical and pathological features such as lymph node metastasis, neural invasion, and tumor infiltration depth. Detection of these biomarkers may have important value in predicting patients' prognosis and survival.
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图 1 SIRT1、CSF1R蛋白在结肠癌组织和癌旁组织中的表达(比例尺100 μm)
A: SIRT1蛋白在癌旁组织中表达; B: SIRT1蛋白在结肠癌组织中表达; C: CSF1R蛋白在癌旁组织中表达; D: CSF1R蛋白在结肠癌组织中表达。
表 1 SIRT1和CSF1R蛋白在结肠癌组织和癌旁组织中的表达情况[n(%)]
组织类型 n SIRT1 CSF1R 高表达 低表达 高表达 低表达 癌旁组织 148 99(66.89) 49(33.11) 53(35.81) 95(64.19) 结肠癌组织 148 43(29.05)* 105(70.95)* 112(75.68)* 36(24.32)* 与癌旁组织相比, * P < 0.05。 
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表 2 SIRT1和CSF1R蛋白与临床病理特征的关系[n(%)]
临床病理特征 分类 n SIRT1低表达(n=105) SIRT1高表达(n=43) χ2 P CSF1R低表达(n=36) CSF1R高表达(n=112) χ2 P 年龄 < 60岁 52 39(37.14) 13(80.23) 0.639 0.424 16(44.44) 36(32.14) 1.809 0.179 ≥60岁 96 66(62.86) 30(69.77) 20(55.56) 76(67.86) 性别 男 81 56(53.33) 25(58.14) 0.284 0.594 23(63.89) 58(51.79) 1.611 0.204 女 67 49(46.67) 18(41.86) 13(36.11) 54(48.21) 肿瘤直径 < 5 cm 69 45(42.86) 24(55.81) 2.058 0.151 19(52.78) 50(44.64) 0.714 0.395 ≥5 cm 79 60(57.14) 19(44.17) 17(47.22) 62(55.36) TNM分期 Ⅰ~Ⅱ期 85 55(52.38) 30(69.77) 3.772 0.052 25(69.44) 60(53.57) 2.808 0.094 Ⅲ~Ⅳ期 63 50(47.62) 13(30.23) 11(30.56) 52(46.43) 淋巴结转移 否 91 57(54.29) 34(79.07) 7.913 0.005 29(80.56) 62(55.36) 7.305 0.007 是 57 48(45.71) 9(20.93) 7(19.44) 50(44.64) 神经侵袭 有 43 38(36.19) 5(11.63) 8.929 0.003 4(11.11) 39(34.82) 7.430 0.006 无 105 67(63.81) 38(88.37) 32(88.89) 73(65.18) 浸润深度 T1~T2期 77 45(42.86) 32(74.42) 12.175 < 0.001 8(22.22) 69(61.61) 16.931 < 0.001 T3~T4期 71 60(57.14) 11(25.58) 28(77.78) 43(38.39)
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表 3 SIRT1和CSF1R蛋白在结肠癌组织中的相关性
SIRT1 CSF1R r P 高表达(n=112) 低表达(n=36) 高表达(n=43) 23 20 -0.536 < 0.001 低表达(n=105) 89 16
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表 4 结肠癌患者预后的影响因素
因素 B SE Wald P HR 95%CI SIRT1 -0.304 0.096 10.015 0.002 0.738 0.614~0.891 CSF1R 1.267 0.412 9.452 0.002 3.549 1.583~7.958 淋巴结转移 0.922 0.364 6.420 0.011 2.515 1.232~5.133 神经侵袭 1.619 0.223 7.704 0.006 1.857 1.199~2.875 浸润深度 0.755 0.296 6.509 0.011 2.128 1.191~3.801
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