ABCG2蛋白的表达与胃癌易感性、预后及化疗敏感性的关系研究
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摘要
目的探讨ABCG2蛋白的表达与胃癌易感性、预后及化疗敏感性的关系。方法选取2015年8月至2017年5月收治的80例胃癌患者为研究对象。采用酶联免疫吸附法(ELISA)法测定胃癌患者癌组织及癌旁正常组织中ABCG2蛋白表达水平。分析胃癌患者癌组织中ABCG2蛋白表达水平与胃癌患者性别比、年龄等一般信息及肿瘤直径、分化程度、癌细胞浸润深度、淋巴结转移之间的相关性。测定并比较胃癌患者化疗前后ABCG2蛋白表达水平,并根据化疗效果,将80例胃癌患者分为完全缓解(CR)、部分缓解(PR)、病情稳定(SD)、疾病进展(PD)组,比较4组患者ABCG2蛋白表达水平。采用多因素Logistic回归分析胃癌患者预后情况的影响因素。结果胃癌患者胃癌组织中ABCG2蛋白表达水平明显高于癌旁正常组织,差异有统计学意义(P <0. 05)。不同性别患者间、不同年龄段、不同浸润深度患者间ABCG2蛋白表达水平差异无统计学意义(P> 0. 05)。肿瘤直径≥5 cm者ABCG2蛋白表达水平明显高于肿瘤直径<5 cm者,低分化者ABCG2蛋白表达水平明显高于中高分化受试者、中分化者高于高分化者,发生淋巴结转移者ABCG2蛋白表达水平明显高于无淋巴结转移者,上述差异均有统计学意义(P <0. 05)。胃癌患者化疗后癌组织中ABCG2蛋白表达水平为明显低于化疗前,化疗效果越差的患者ABCG2蛋白表达水平越高,且差异有统计学意义(P <0. 05)。多因素Logistic回归分析结果显示,肿瘤直径、分化程度、淋巴结转移、ABCG2蛋白表达水平与胃癌患者预后显著相关(P <0. 05)。结论 ABCG2蛋白的表达水平与胃癌的发生、发展及化疗效果密切相关。
Objective To investigate the correlation between the expression of ABCG2 protein and the susceptibility,prognosis,chemotherapeutic sensitivity of gastric cancer. Methods A total of 80 patients with gastric cancer who were admitted and treated in our hospital from August 2015 to May 2017 were selected as the subjects. The expression levels of ABCG2 protein in cancer tissues and normal tissues adjacent to the cancer tissues of patients with gastric cancer were detected by ELISA. The correlation between expression level of ABCG2 protein with general information such as sex ratio,age as well as tumor diameter,differentiated degree,the depth of cancer cell invasion,lymphatic metastasis in patients with gastric cancer were observed and analyzed. The expression level of ABCG2 protein before and after chemotherapy in patients with gastric cancer were measured. And according to the effects of chemotherapy,the 80 patients with gastric cancer were divided into CR,PR,SD,PD group,the expression levels of ABCG2 in the four groups were observed and compared. The factors influencing prognosis of gastric cancer patients were analyzed by multifactor Logistic regression. Results The expression levels of ABCG2 protein in gastric cancer tissue of patients were significantly higher than those in normal tissues adjacent to gastric tissue( P < 0. 05). There were no significant differences in the expression levels of ABCG2 protein in gastric cancer patients with different genders,ages,and the depth of invasion( P > 0. 05). The expression level of ABCG2 protein in patients whose tumor diameter≥5 cm was significantly higher than that in patients whose tumor diameter < 5cm( P < 0. 05). The expression level of ABGG2 protein in poorly differentiated patients were significantly higher than those in medium to high differentiated patients( P < 0. 05),moreover the expression level of ABGG2 protein in moderately differentiated patients were significantly higher than those in high differentiation( P < 0. 05). The expression level of ABCG2 protein in patients who had lymphatic metastasis was significantly higher than that in patients who had no lymphatic metastasis( P < 0. 05). The expression levels of ABCG2 protein in patients with gastric cancer after chemotherapy were significantly lower than those before chemotherapy( P < 0. 05). And the higher the expression levels of ABCG2 protein,the worse the effects of chemotherapy( P < 0. 05).Multifactor Logistic regression analysis showed that the tumor diameter,differentiated degrees,lymphatic metastasis,the expression level of ABCG2 protein were significantly correlated with the prognosis of patients with gastric cancer( P < 0. 05).Conclusion The expression levels of ABCG2 protein are closely related to the occurrence,development and chemotherapy effects of gastric cancer.
Objective To investigate the correlation between the expression of ABCG2 protein and the susceptibility,prognosis,chemotherapeutic sensitivity of gastric cancer. Methods A total of 80 patients with gastric cancer who were admitted and treated in our hospital from August 2015 to May 2017 were selected as the subjects. The expression levels of ABCG2 protein in cancer tissues and normal tissues adjacent to the cancer tissues of patients with gastric cancer were detected by ELISA. The correlation between expression level of ABCG2 protein with general information such as sex ratio,age as well as tumor diameter,differentiated degree,the depth of cancer cell invasion,lymphatic metastasis in patients with gastric cancer were observed and analyzed. The expression level of ABCG2 protein before and after chemotherapy in patients with gastric cancer were measured. And according to the effects of chemotherapy,the 80 patients with gastric cancer were divided into CR,PR,SD,PD group,the expression levels of ABCG2 in the four groups were observed and compared. The factors influencing prognosis of gastric cancer patients were analyzed by multifactor Logistic regression. Results The expression levels of ABCG2 protein in gastric cancer tissue of patients were significantly higher than those in normal tissues adjacent to gastric tissue( P < 0. 05). There were no significant differences in the expression levels of ABCG2 protein in gastric cancer patients with different genders,ages,and the depth of invasion( P > 0. 05). The expression level of ABCG2 protein in patients whose tumor diameter≥5 cm was significantly higher than that in patients whose tumor diameter < 5cm( P < 0. 05). The expression level of ABGG2 protein in poorly differentiated patients were significantly higher than those in medium to high differentiated patients( P < 0. 05),moreover the expression level of ABGG2 protein in moderately differentiated patients were significantly higher than those in high differentiation( P < 0. 05). The expression level of ABCG2 protein in patients who had lymphatic metastasis was significantly higher than that in patients who had no lymphatic metastasis( P < 0. 05). The expression levels of ABCG2 protein in patients with gastric cancer after chemotherapy were significantly lower than those before chemotherapy( P < 0. 05). And the higher the expression levels of ABCG2 protein,the worse the effects of chemotherapy( P < 0. 05).Multifactor Logistic regression analysis showed that the tumor diameter,differentiated degrees,lymphatic metastasis,the expression level of ABCG2 protein were significantly correlated with the prognosis of patients with gastric cancer( P < 0. 05).Conclusion The expression levels of ABCG2 protein are closely related to the occurrence,development and chemotherapy effects of gastric cancer.
引文
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2 Zhang L,Guo X,Zhang D,et al.Upregulated miR-132 in Lgr5+gastric cancer stem cell-like cells contributes to cisplatin-resistance via SIRT1/CREB/ABCG2 signaling pathway.Mol Carcinog,2017,56:2022-2034.
3 Wang J,Yunyun Z,Wang L,et al.ABCG2 confers promotion in gastric cancer through modulating downstream CRKL in vitro combining with biostatistics mining.Oncotarget,2017,8:5256-5267.
4 Wang DS,Patel A,Shukla S,et al.Icotinib antagonizes ABCG2-mediated multidrug restance,but not the pemetrexed resistance mediated by thymidylate synthase and ABCG2.Oncotarget,2014,5:4529-4542.
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6 Lin PC,Lin HH,Lin JK,et al.Expression of ABCG2 associated with tumor response in metastatic colorectal cancer patients receiving first-line FOLFOX therapy-preliminary evidence.Int J Biol Markers,2013,28:182-186.
7 Wang J,Gan C,Sparidans RW,et al.P-glycoprotein(MDR1/ABCB1)and Breast Cancer Resistance Protein(BCRP/ABCG2)affect brain accumulation and intestinal disposition of encorafenib in mice.Pharmacol Res,2017,129:414-423.
8 Guan GF,Zhang DJ,Zheng Y,et al.Abnormal Wnt signaling and overexpression of ABCG2 contributes to drug efflux properties of side population cells in nasopharyngeal carcinoma.Mol Med Rep,2015,12:4352-4357.
9 Hira D,Terada T.BCRP/ABCG2 and high-alert medications:Biochemical,pharmacokinetic,pharmacogenetic,and clinical implications.Biochem Pharmacol,2017,147:201-210.
10 Hu B,Zhang H,Wang Z,et al.LncRNA CCAT1/miR-130a-3p axis increases cisplatin resistance in non-small-cell lung cancer cell line by targeting SOX4.Cancer Biol Ther,2017,11:1-10.
11 Wagmann L,Maurer HH,Meyer MR.An easy and fast adenosine 5'-diphosphate quantification procedure based on hydrophilic interaction liquid chromatography-high resolution tandem mass spectrometry for determination of the in vitro adenosine 5'-triphosphatase activity of the human breast cancer resistance protein ABCG2.J Chromatogr A,2017,1521:123-130.
12 Liu D,Wu N,Sun H,et al.ABCG2 and NCF4 polymorphisms are associated with clinical outcomes in diffuse large B-cell lymphoma patients treated with R-CHOP.Oncotarget,2017,8:58292-58303.
13 Wei H,Liang F,Cheng W,et al.The mechanisms for lung cancer risk of PM2.5:Induction of epithelial-mesenchymal transition and cancer stem cell properties in human non-small cell lung cancer cells.Environ Toxicol,2017,32:2341-2351.
14 Olsen CE,Weyergang A,Edwards VT,et al.Development of resistance to photodynamic therapy(PDT)in human breast cancercells is photosensitizer-dependent:Possible mechanisms and approaches for overcoming PDT-resistance.Biochem Pharmacol,2017,144:63-77.
15 Sun J,Zhu M,Shen W,et al.A potentially functional polymorphism in ABCG2 predicts clinical outcome of non-small cell lung cancer in a Chinese population.Pharmacogenomics J,2017,17:280-285.
16 Chua VY,Larma I,Harvey J,et al.Activity of ABCG2 Is Regulated by Its Expression and Localization in DHT and Cyclopamine-Treated Breast Cancer Cells.J Cell Biochem,2016,117:2249-2259.
17 Ghafouri H,Ghaderi B,Amini S,et al.Association of ABCB1 and ABCG2 single nucleotide polymorphisms with clinical findings and response to chemotherapy treatments in Kurdish patients with breast cancer.Tumour Biol,2016,37:7901-7906.
18 Hofman J,Ku8era R,Neumanova Z,et al.Placental passage of olomoucine II,but not purvalanol A,is affected by p-glycoprotein(ABCB1),breast cancer resistance protein(ABCG2)and multidrug resistance-associated proteins(ABCCs).Xenobiotica,2016,46:416-423.
19 Salimizand H,Amini S,Abdi M,et al.Concurrent effects of ABCB1C3435T,ABCG2 C421A,and XRCC1 Arg194Trp genetic polymorphisms with risk of cancer,clinical output,and response to treatment with imatinib mesylate in patients with chronic myeloid leukemia.Tumour Biol,2016,37:791-798.
20 Napoletano C,Bellati F,Ruscito I,et al.Immunological and Clinical Impact of Cancer Stem Cells in Vulvar Cancer:Role of CD133/CD24/ABCG2-Expressing Cells.Anticancer Res,2016,36:5109-5116.
2 Zhang L,Guo X,Zhang D,et al.Upregulated miR-132 in Lgr5+gastric cancer stem cell-like cells contributes to cisplatin-resistance via SIRT1/CREB/ABCG2 signaling pathway.Mol Carcinog,2017,56:2022-2034.
3 Wang J,Yunyun Z,Wang L,et al.ABCG2 confers promotion in gastric cancer through modulating downstream CRKL in vitro combining with biostatistics mining.Oncotarget,2017,8:5256-5267.
4 Wang DS,Patel A,Shukla S,et al.Icotinib antagonizes ABCG2-mediated multidrug restance,but not the pemetrexed resistance mediated by thymidylate synthase and ABCG2.Oncotarget,2014,5:4529-4542.
5 Vadlapatla RK,Vadlapudi AD,Pal D,et al.Mechanisms of drug resistance in cancer chemotherapy:coordinated role and regulation of efflux transporters and metabolizing enzymes.Curr Pharm Des,2013,19:7126-7140.
6 Lin PC,Lin HH,Lin JK,et al.Expression of ABCG2 associated with tumor response in metastatic colorectal cancer patients receiving first-line FOLFOX therapy-preliminary evidence.Int J Biol Markers,2013,28:182-186.
7 Wang J,Gan C,Sparidans RW,et al.P-glycoprotein(MDR1/ABCB1)and Breast Cancer Resistance Protein(BCRP/ABCG2)affect brain accumulation and intestinal disposition of encorafenib in mice.Pharmacol Res,2017,129:414-423.
8 Guan GF,Zhang DJ,Zheng Y,et al.Abnormal Wnt signaling and overexpression of ABCG2 contributes to drug efflux properties of side population cells in nasopharyngeal carcinoma.Mol Med Rep,2015,12:4352-4357.
9 Hira D,Terada T.BCRP/ABCG2 and high-alert medications:Biochemical,pharmacokinetic,pharmacogenetic,and clinical implications.Biochem Pharmacol,2017,147:201-210.
10 Hu B,Zhang H,Wang Z,et al.LncRNA CCAT1/miR-130a-3p axis increases cisplatin resistance in non-small-cell lung cancer cell line by targeting SOX4.Cancer Biol Ther,2017,11:1-10.
11 Wagmann L,Maurer HH,Meyer MR.An easy and fast adenosine 5'-diphosphate quantification procedure based on hydrophilic interaction liquid chromatography-high resolution tandem mass spectrometry for determination of the in vitro adenosine 5'-triphosphatase activity of the human breast cancer resistance protein ABCG2.J Chromatogr A,2017,1521:123-130.
12 Liu D,Wu N,Sun H,et al.ABCG2 and NCF4 polymorphisms are associated with clinical outcomes in diffuse large B-cell lymphoma patients treated with R-CHOP.Oncotarget,2017,8:58292-58303.
13 Wei H,Liang F,Cheng W,et al.The mechanisms for lung cancer risk of PM2.5:Induction of epithelial-mesenchymal transition and cancer stem cell properties in human non-small cell lung cancer cells.Environ Toxicol,2017,32:2341-2351.
14 Olsen CE,Weyergang A,Edwards VT,et al.Development of resistance to photodynamic therapy(PDT)in human breast cancercells is photosensitizer-dependent:Possible mechanisms and approaches for overcoming PDT-resistance.Biochem Pharmacol,2017,144:63-77.
15 Sun J,Zhu M,Shen W,et al.A potentially functional polymorphism in ABCG2 predicts clinical outcome of non-small cell lung cancer in a Chinese population.Pharmacogenomics J,2017,17:280-285.
16 Chua VY,Larma I,Harvey J,et al.Activity of ABCG2 Is Regulated by Its Expression and Localization in DHT and Cyclopamine-Treated Breast Cancer Cells.J Cell Biochem,2016,117:2249-2259.
17 Ghafouri H,Ghaderi B,Amini S,et al.Association of ABCB1 and ABCG2 single nucleotide polymorphisms with clinical findings and response to chemotherapy treatments in Kurdish patients with breast cancer.Tumour Biol,2016,37:7901-7906.
18 Hofman J,Ku8era R,Neumanova Z,et al.Placental passage of olomoucine II,but not purvalanol A,is affected by p-glycoprotein(ABCB1),breast cancer resistance protein(ABCG2)and multidrug resistance-associated proteins(ABCCs).Xenobiotica,2016,46:416-423.
19 Salimizand H,Amini S,Abdi M,et al.Concurrent effects of ABCB1C3435T,ABCG2 C421A,and XRCC1 Arg194Trp genetic polymorphisms with risk of cancer,clinical output,and response to treatment with imatinib mesylate in patients with chronic myeloid leukemia.Tumour Biol,2016,37:791-798.
20 Napoletano C,Bellati F,Ruscito I,et al.Immunological and Clinical Impact of Cancer Stem Cells in Vulvar Cancer:Role of CD133/CD24/ABCG2-Expressing Cells.Anticancer Res,2016,36:5109-5116.