SPARCL1表达下调对胆囊癌吉西他滨耐药的作用机制及临床意义

The mechanism and clinical significance of SPARCL1 down-regulation expression on gemcitabine resistance in gallbladder cancer

目的研究富含半胱氨酸酸性分泌型糖蛋白类似物1(SPARCL1)在胆囊癌中的作用。方法将人胆囊癌吉西他滨耐药细胞株GBC-SD/GEM分为空白对照组和SPARCL1过表达转染组。检测转染后SPARCL1表达、各细胞增殖能力及基质金属蛋白酶-9(MMP-9)、波形蛋白(VIM)、纤维连接蛋白1(FN1)表达;检测2014年1月—2017年1月在洛阳中心医院行手术治疗的50例胆囊癌(吉西他滨耐药组、敏感组)及癌旁组织中SPARCL1表达,分析其与患者临床病理特征及预后间的关系。结果转染组SPARCL1基因相对表达量(29.12±1.10)及蛋白相对表达量(23.08±2.15)均显著高于空白对照组(3.34±0.98、2.58±0.71,均P<0.05)。转染组细胞增殖数及MMP-9、VIM、FN1相对表达量分别为33.09±12.11、1.69±0.75、1.78±0.43、1.62±0.31,均低于对照组(327.15±9.28、3.81±0.78、4.12±0.24、4.69±0.63,均P<0.05)。耐药组、敏感组及癌旁组织中SPARCL1表达量分别为5.65±2.01、15.02±1.17、28.46±2.53,组间差异有统计学意义(P<0.05)。SPARCL1表达与性别、年龄、病理类型、肿瘤大小、CA19-9、CEA和肿瘤分期无相关性(均P>0.05),而与淋巴结转移和肿瘤分化程度有相关性(均P<0.05)。耐药组患者中位生存期明显低于敏感组(14.77个月vs.27.28个月)。结论SPARCL1在胆囊癌中低表达,且与吉西他滨化疗耐药及预后相关。

Objective To examine the role of cysteine rich acidic secretory glycoprotein analogue 1(SPARCL1)in gallbladder cancer.Methods Gemcitabine resistant human gallbladder carcinoma cell line GBC-SD/GEM cell line was divided into blank control and SPARCL1 overexpression transfection groups.The expression levels of SPARCL1,matrix metalloproteinase-9(MMP-9),vimentin(VIM)and fibronectin 1(FN1),and the proliferation ability of each cell was detected after transfection.The expression of SPARCL1 in 50 cases of gallbladder cancer(gemcitabine-resistant group and-sensitive group)and paracancerous tissues operated in Luoyang Central Hospital from January 2014 to January 2017 were detected,and its relationship with the clinicopathologic features and prognoses of patients were analysed.Results The expression of SPARCL1 gene(29.12±1.10)and SPARCL1 protein(23.08±2.15)in the transfection group were significantly higher than that in the control group respectively(3.34±0.98,2.58±0.71,all P<0.05).The proliferation capacities and expression levels of MMP-9,VIM and FN1 in the SPARCL1 transfection group were 33.09±12.11,1.69±0.75,1.78±0.43 and 1.62±0.31,which were all significantly lower than those in the control group(327.15±9.28,3.81±0.78,4.12±0.24,4.69±0.63,all P<0.05).The expression of SPARCL1 in gemcitabine resistance group,sensitive group and paracancerous tissues were 5.65±2.01,15.02±1.17 and 28.46±2.53,respectively,the difference between groups was significant(P<0.05).SPARCL1 expression was independent of gender,age,pathological type,tumour size,CA19-9,CEA and tumour stage(all P>0.05),but significantly correlated with lymph node metastasis and tumour differentiation(all P<0.05).Median survival time of patients in the gemcitabine-resistant group was significantly lower than that of the sensitive group(14.77 months vs.27.28 months).Conclusion SPARCL1 is poorly expressed in gallbladder cancer and is associated with gemcitabine chemotherapy resistance and prognosis.