Correlation of ABCG2 expression with the efficacy of irinotecan chemotherapy in colorectal cancer patients
-
摘要:
目的 明确结直肠癌组织中ABCG2(ATP-binding cassette superfamily G member 2,ABCG2)的表达及其与患者临床病理特征、以伊立替康(CPT-11)为基础化疗疗效的相关性,从而为结直肠癌患者实现个体化治疗提供理论依据。 方法 筛选1996年1月至2011年12月于北京大学肿瘤医院行CPT-11化疗的晚期结直肠癌患者,收集患者完整病史资料及肿瘤组织样本。用免疫组织化学的方法检测样本中ABCG2蛋白表达情况。分析ABCG2蛋白表达与患者临床病理特征、CPT-11化疗疗效的相关性。 结果 1)免疫组织化学染色显示ABCG2在结直肠癌组织中表达阳性率达93.2%,癌旁正常肠黏膜ABCG2蛋白阳性表达率为43.6%,癌组织较癌旁正常黏膜组织的表达水平明显增高(P < 0.05)。ABCG2表达与患者年龄、性别、病理分化程度、病变部位、肝转移均无明显相关性。2)ABCG2蛋白表达与CPT-11化疗疗效无显著相关(P>0.05)。 结论 在应用伊立替康为基础方案化疗的结直肠癌患者中,癌组织中ABCG2蛋白表达水平与患者化疗疗效无明显相关。 Abstract:Objective To identify the ABCG2 expression levels in colorectal cancer patients and its relationship with clinicopathological features and the efficacy of irinotecan-based chemotherapy and to provide further theoretical basis for individualized treatment. Methods Clinical data and tumor samples from patients with metastatic CRC who have received irinotecan-based chemotherapy at the Department of Gastroenterological Oncology, Peking University Cancer Hospital from January 1996 to December 2011 were collected. The immunohistochemical method was used to detect ABCG2 expression levels both in colorectal carcinoma and tumor-adjacent normal tissues. The correlations of the expression of ABCG2 with clinicopathological features and the efficacy of irinotecan-based chemotherapy were statistically analyzed. Results 1) Immunohistochemical staining shows that the positive rate of ABCG2 expression in the colorectal cancer samples is 93.2%, which is significantly higher than that in normal colon mucosa at 43.6% (P < 0.05). No significant associations were observed between ABCG2 expression and age, gender, tumor differentiation, primary tumor sites, or liver metastasis.(2) ABCG2 expression has no significant correlation with the efficacy of irinotecan-based chemotherapy (P>0.05). Conclusion ABCG2 expression has no significant correlation with the efficacy of irinotecan chemotherapy in patients with colorectal cancer. -
Key words:
- ABCG2 /
- CPT-11 /
- colorectal cancer
-
表 1 患者基本资料
Table 1. Basic data of the patients
表 2 结直肠癌组织ABCG2表达与临床病理变量的关系
Table 2. Association of the ABCG2 protein with the clinicopathological features of colorectal cancer
表 3 结直肠癌组织ABCG2表达与伊立替康为基础化疗疗效的相关性
Table 3. Association of the ABCG2 protein with the efficacy of irinote-can-based chemotherapy
表 4 结直肠癌组织ABCG2表达与FOLFIRI方案化疗疗效的相关性
Table 4. Association of the ABCG2 protein with the efficacy of FOLFIRI chemotherapy
-
[1] Robey RW, Ierano C, Zhan Z, et al. The challenge of exploiting ABCG2 in the clinic[J]. Curr Pharm Biotechnol, 2011, 12(4):595-608. http://www.tandfonline.com/servlet/linkout?suffix=CIT0029&dbid=8&doi=10.1080%2F00498254.2017.1328147&key=21118093 [2] Takara K, Kitada N, Yoshikawa E, et al. Molecular changes to HeLa cells on continuous exposure to SN-38, an active metabolite of irinotecan hydrochloride[J]. Cancer Lett, 2009, 278(1):88-96. doi: 10.1016/j.canlet.2008.12.033 [3] Sun YL, Patel A, Kumar P, et al. Role of ABC transporters in cancer chemotherapy[J]. Chin J Cancer, 2012, 31(2):51-57. doi: 10.5732/cjc.011.10466 [4] Mo W, Zhang JT. Human ABCG2: structure, function, and its role in multidrug resistance[J]. Int J Biochem Mol Biol, 2012, 3(1):1-27. http://www.ncbi.nlm.nih.gov/pubmed/22509477 [5] Natarajan K, Xie Y, Baer MR, et al. Role of breast cancer resistance protein (BCRP/ABCG2) in cancer drug resistance[J]. Biochem Pharmacol, 2012, 83(8):1084-1103. doi: 10.1016/j.bcp.2012.01.002 [6] Gupta N, Martin PM, Miyauchi S, et al. Down-regulation of BCRP/ ABCG2 in colorectal and cervical cancer[J]. Biochem Biophys Res Commun, 2006, 343(2):571-577. http://www.ncbi.nlm.nih.gov/pubmed/16554028 [7] Wang X, Xia B, Liang Y, et al. Membranous ABCG2 expression in colorectal cancer independently correlates with shortened patient survival[J]. Cancer Biomark, 2013, 13(2):81-88. doi: 10.3233/CBM-130344 [8] Liu HG, Pan YF, You J, et al. Expression of ABCG2 and its significance in colorectal cancer[J]. Asian Pac J Cancer Prev, 2010, 11(4): 845-848. http://www.ncbi.nlm.nih.gov/pubmed/21133588 [9] 李刚强, 朱瑞, 周海亚, 等.ABCG2和CD44V6在大肠癌中的表达及临床意义[J].实用癌症杂志, 2012, 27(1):27-29. http://www.cqvip.com/QK/94147X/201201/40820619.htmlLi GQ, Zhu R, Zhou HY, et al. Expression of ABCG2 and CD44V6 in the colorectal cancer and clinical significance[J]. The Practical Journal of Cancer, 2012, 27(1):27-29. http://www.cqvip.com/QK/94147X/201201/40820619.html [10] 胡潇红, 沙卫红, 林锋, 等.大肠癌组织中ABCG2的表达及临床病理意义[J].中华临床医师杂志, 2011, 5(12):3436-3460. http://d.wanfangdata.com.cn/Periodical_zhlcyszz201112009.aspxHu XH, Sha WH, Lin F, et al. The correlation between the expressions of ABCG2 and clinicopathological parameters of colorectal cancer[J]. Chin J Clinicians, 2011, 5(12):3436-3460. http://d.wanfangdata.com.cn/Periodical_zhlcyszz201112009.aspx [11] 赵亚超, 张志培, 韩勇, 等.非小细胞肺癌组织BCRP和GST-π表达及其与化疗敏感性关系的研究[J].中华肿瘤防治杂志, 2008, 15(12): 897-900. http://doi.med.wanfangdata.com.cn/qk/qlzlzz200812006Zhao YC, Zhang ZP, Han Y, et al. Relationship between expressions of BCRP and GST-π in non-small cell lung cancer and drug sensitivity[J]. Chin J Cancer Prev Treat, 2008, 15(12):897-900. http://doi.med.wanfangdata.com.cn/qk/qlzlzz200812006 [12] Damiani D, Tiribelli M, Michelutti A, et al. Fludarabine-based induction therapy does not overcome the negative effect of ABCG2 (BCRP) over-expression in adult acute myeloid leukemia patients [J]. Leuk Res, 34(7):942-945. doi: 10.1016/j.leukres.2010.01.008 [13] Kim YH, Ishii G, Goto K, et al. Expression of breast cancer resistance protein is associated with a poor clinical outcome in patients with small-cell lung cancer[J]. Lung Cancer, 2009, 65(1):105-111. http://www.sciencedirect.com/science/article/pii/S0169500208005217 [14] Omran OM. The prognostic value of breast cancer resistance protein (BCRB/ABCG2) expression in breast carcinomas[J]. J Environ Pathol Toxicol Oncol, 2012, 31(4):367-376. doi: 10.1615/JEnvironPatholToxicolOncol.2013006767 [15] Zhang G, Wang Z, Luo W, et al. Expression of Potential Cancer Stem Cell Marker ABCG2 is Associated with Malignant Behaviors of Hepatocellular Carcinoma[J]. Gastroenterol Res Pract, 2013, 2013: 782581. http://europepmc.org/abstract/med/24194752 [16] de Lima LT, Vivona D, Bueno CT, et al. Reduced ABCG2 and increased SLC22A1 mRNA expression are associated with imatinib response in chronic myeloid leukemia[J]. Med Oncol, 2014, 31(3):851. doi: 10.1007/s12032-014-0851-5 [17] Zhang Q, Li K, Xu JH, et al. Role of ABCG2 expression driven by cisplatin in platinum-containing chemotherapy for gastric cancer[J]. World J Gastroenterol, 2013, 19(39):6630-6636. doi: 10.3748/wjg.v19.i39.6630 [18] Mo W, Zhang JT. Human ABCG2: structure, function, and its role in multidrug resistance[J]. Int J Biochem Mol Biol, 2012, 3(1):1-27. http://www.ncbi.nlm.nih.gov/pubmed/22509477 [19] Svirnovski AI, Shman TV, Serhiyenka TF, et al. ABCB1 and ABCG2 proteins, their functional activity and gene expression in concert with drug sensitivity of leukemia cells[J]. Hematology, 2009, 14(4):204-212. http://www.europepmc.org/abstract/MED/19635183