直肠癌患者手术前后血清基质金属蛋白酶9、瘦素及基质金属蛋白酶抑制剂1的变化
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摘要
目的探讨直肠癌患者手术前后血清基质金属蛋白酶(matrix metalloproteinase,MMP) 9、瘦素(leptin)和基质金属蛋白酶抑制剂(tissue inhibitor of metallopro teinases,TIMP) 1表达情况及其与结直肠癌局部复发及预后的相关性。方法收集绵阳市中心医院接受手术治疗的直肠癌患者150例的临床资料,所有患者术前、术后10 d均测定MMP9、leptin、TIMP1水平,且完成术后3年随访调查,分析MMP9、leptin、TIMP1表达与直肠癌临床病理及预后的关系。结果术后10 d,所有直肠癌患者MMP9、leptin、TIMP1水平均降低(P<0. 05); Dukes分期为C期+D期、肿瘤侵犯浆膜层、合并淋巴结转移、术后未接受辅助治疗、术后复发/转移及术后3年死亡患者MMP9、leptin、TIMP1水平分别高于Dukes分期为A期+B期、肿瘤未侵犯浆膜层、无淋巴结转移、术后接受辅助治疗、术后未复发/转移及术后3年生存患者(P<0. 05); MMP9、leptin、TIMP1 3者表达均互呈正相关,3者与直肠癌Dukes分期、肿瘤浸润深度、淋巴结转移、术后复发/转移呈正相关(P<0. 05),与术后辅助治疗及患者术后3年生存率呈负相关(P<0. 05)。结论直肠癌患者血清MMP9、leptin、TIMP1均呈过度表达,术后上述各因子水平均降低,3者表达均与直肠癌肿瘤恶性生物学行为及患者预后均存在密切关联,可作为评估手术疗效及患者预后的依据。
Objective To investigate the expression of serum matrix metalloproteinase( MMP) 9,leptin and tissue inhibitor of metalloproteinase( TIMP) 1 in patients with rectal cancer before and after operation,and their correlation with local recurrence and prognosis of colorectal cancer. Methods The clinical data of 150 patients with rectal cancer treated by operation were collected. The levels of MMP9,leptin and TIMP1 were determined before operation and at 10 days after operation. All patients were followed up for 3 years. The relationship between expression of MMP9,leptin and TIMP1 and the clinicopathological data and prognosis were analyzed. Results Levels of MMP9,leptin and TIMP1 in all patients decreased at 10 days after operation( P<0. 05).Levels of MMP9,leptin and TIMP1 were higher in patients at Dukes stage C+stage D,tumor invading the serosal layer,lymph node metastasis,no postoeprative adjuvant therapy,postoperative recurrence/metastasis and died in 3 years after operation were higher than those in patients at Dukes stage A+stage B,without invading the serosal layer,without lymph node metastasis,with postoperative adjuvant treatment,postoperative recurrence/metastasis and survived in 3 years after operation( P<0. 05). The expression of MMP9,leptin or TIMP1 was positively correlated with each other.The three markers were positively correlated with the Dukes stage,depth of tumor invasion,lymph node metastasis and postoperative recurrence/metastasis( P<0. 05),and negatively correlated with postoperative adjuvant therapy and postoperative 3 year survival rate( P < 0. 05). Conclusion MMP9,leptin and TIMP1 show up-expression in serum of patients with rectal cancer,while they decrease after operation. The expression is closely related to malignant biological behavior and prognosis. They can be used as the basis for evaluating the curative effect and prognosis.
Objective To investigate the expression of serum matrix metalloproteinase( MMP) 9,leptin and tissue inhibitor of metalloproteinase( TIMP) 1 in patients with rectal cancer before and after operation,and their correlation with local recurrence and prognosis of colorectal cancer. Methods The clinical data of 150 patients with rectal cancer treated by operation were collected. The levels of MMP9,leptin and TIMP1 were determined before operation and at 10 days after operation. All patients were followed up for 3 years. The relationship between expression of MMP9,leptin and TIMP1 and the clinicopathological data and prognosis were analyzed. Results Levels of MMP9,leptin and TIMP1 in all patients decreased at 10 days after operation( P<0. 05).Levels of MMP9,leptin and TIMP1 were higher in patients at Dukes stage C+stage D,tumor invading the serosal layer,lymph node metastasis,no postoeprative adjuvant therapy,postoperative recurrence/metastasis and died in 3 years after operation were higher than those in patients at Dukes stage A+stage B,without invading the serosal layer,without lymph node metastasis,with postoperative adjuvant treatment,postoperative recurrence/metastasis and survived in 3 years after operation( P<0. 05). The expression of MMP9,leptin or TIMP1 was positively correlated with each other.The three markers were positively correlated with the Dukes stage,depth of tumor invasion,lymph node metastasis and postoperative recurrence/metastasis( P<0. 05),and negatively correlated with postoperative adjuvant therapy and postoperative 3 year survival rate( P < 0. 05). Conclusion MMP9,leptin and TIMP1 show up-expression in serum of patients with rectal cancer,while they decrease after operation. The expression is closely related to malignant biological behavior and prognosis. They can be used as the basis for evaluating the curative effect and prognosis.
引文
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[14]Zhao H,Xu Z,Qin H,et al.miR-30b regulates migration and invasion of human colorectal cancer via SIX1[J].Biochem J,2014,460(1):117-125.
[15]Wieczorek E,Reszka E,Jablonowski Z,et al.Genetic polymorphisms in matrix metalloproteinases(MMPs)and tissue inhibitors of MPs(TIMPs),and bladder cancer susceptibility[J].BJU Int,2013,112(8):1207-1214.
[16]Yoon KW,Park SY,Kim JY,et al. Leptin-induced adhesion and invasion in colorectal cancer cell lines[J].Oncol Rep,2014,31(6):2493-2498.
[17]陈燕,陈明卫.脂肪因子与结直肠癌[J].国际肿瘤学杂志,2015,42(1):67-70.
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[3]Pommier AJ,Farren M,Patel B,et al.Leptin,BMI,and a metabolic gene expression signature associated with clinical outcome to VEGF inhibition in colorectal cancer[J].Cell Metab,2016,23(1):77-93.
[4]Gialamas SP,Sergentanis TN,Antonopoulos CN,et al.Circulating leptin levels and risk of colorectal cancer and adenoma:a case-control study and meta-analysis[J]. Cancer Causes Control,2013,24(12):2129-2141.
[5]Aleksandrova K,Boeing H,Jenab M,et al.Leptin and soluble leptin receptor in risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition cohort[J].Cancer Res,2012,72(20):5328-5337.
[6]张生军,刘敏丽,常琦,等.瘦素及其受体在结直肠癌和转移性结直肠癌中的表达及临床意义[J].中华实验外科杂志,2015,32(8):1986-1988.
[7]向德森,黄俊,熊亚立.瘦素与结直肠癌发生的相关性研究进展[J].重庆医学,2017,46(24):3427-3430.
[8]赖晓东,向德森,黄俊,等.癌胚抗原、脂联素联合瘦素在结直肠癌中的诊断价值[J].重庆医学,2017,46(25):3494-3495,3499.
[9]王雅琴,陈智.载脂蛋白E对结直肠癌细胞侵袭迁移能力的影响[J].肿瘤防治研究,2015,42(12):1198-1201.
[10]Li W,Li S,Deng L,et al.Decreased MT1-MMP in gastric cancer suppressed cell migration and invasion via regulating MMPs and EMT[J]. Tumour Biol,2015,36(9):6883-6889.
[11]吴肖,王爱军,王红钰,等.结直肠癌侵袭转移与双向调节因子的关系及其作用机制[J].中华实验外科杂志,2016,33(11):2569-2572.
[12]Spindler KL,Christensen IJ,Nielsen HJ,et al.TIMP-1 and CEA as biomarkers in third-line treatment with irinotecan and cetuximab for metastatic colorectal cancer[J].Tumour Biol,2015,36(6):4301-4308.
[13]王欣,丁修冬,李潇.血清TSGF的水平与结肠癌诊断及术后疗效的关系[J].标记免疫分析与临床,2013,20(5):288-290.
[14]Zhao H,Xu Z,Qin H,et al.miR-30b regulates migration and invasion of human colorectal cancer via SIX1[J].Biochem J,2014,460(1):117-125.
[15]Wieczorek E,Reszka E,Jablonowski Z,et al.Genetic polymorphisms in matrix metalloproteinases(MMPs)and tissue inhibitors of MPs(TIMPs),and bladder cancer susceptibility[J].BJU Int,2013,112(8):1207-1214.
[16]Yoon KW,Park SY,Kim JY,et al. Leptin-induced adhesion and invasion in colorectal cancer cell lines[J].Oncol Rep,2014,31(6):2493-2498.
[17]陈燕,陈明卫.脂肪因子与结直肠癌[J].国际肿瘤学杂志,2015,42(1):67-70.