趋化因子受体CCR4在结肠、直肠癌中的表达及相关功能
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摘要
目的探讨趋化因子受体CCR4在结肠、直肠癌中的表达及相关功能。方法选取结肠、直肠癌原发灶外科手术标本41例为实验组。选取同期良性良性结肠直肠肿瘤患者30例为对照组。比较免疫组化二步法与RT-PCR法检测趋化因子受体CCR4在结肠、直肠癌组织的阳性率。比较免疫组化二步法、RT-PCR法检测趋化因子受体CCR4与临床各病理因素的关系。结果实验组中免疫组化法检测阳性患者比例显著高于对照组中免疫组化法检测阳性患者比例(P <0. 05);实验组中RT-PCR法检测阳性患者比例显著高于对照组中RT-PCR法检测阳性患者比例(P <0. 05);实验组PCR条带灰度比值显著高于对照组PCR条带灰度比值(P <0. 05)。结肠癌肿瘤组织中CCR4阳性检测表达水平在性别、不同年龄、分化程度、淋巴结转移、肝转移、部位等临床病理因素无显著差异(P> 0. 05)。结肠癌肿瘤组织中CCR4阳性检测表达水平中Duke分期存在显著差异(P <0. 05)。结论病理检测可提示患者Duke分期情况,结肠癌肿瘤组织中CCR4在患者机体免疫调节中具有重要作用。
Objective To investigate the expression and function of chemokine receptor CCR4 in colorectal cancer. Methods Totally 41 surgical specimens of primary colorectal cancer were collected as experimental group,and 30 cases with benign colorectal tumors were selected as control group. Positive rate of chemokine receptor CCR4 in colorectal cancer tissues was compared between two-step immunohistochemistry and RT-PCR. Relationship between chemokine receptor CCR4 and clinicopathological factors was compared by detection of two-step immunohistochemistry or RT-PCR. Results The proportion of positive patients detected by immunohistochemistry in the experimental group was significantly higher than that detected by immunohistochemistry in the control group(P < 0. 05). The proportion of positive patients detected by RT-PCR in the experimental group was significantly higher than that detected by RT-PCR in the control group(P < 0. 05). The gray scale ratio of PCR bands in the experimental group was significantly higher than that in the control group(P < 0. 05). The expressions of CCR4 in colon cancer tissues showed no significant differences in gender,age,degree of differentiation,lymph node metastasis,liver metastasis,location and other clinicopathological factors(P > 0. 05). There was significant difference in CCR4 positive expression in different Duke stages in colon cancer tissues(P < 0. 05). Conclusion Pathological examination can indicate the Duke stage of the patients. CCR4 plays an important role in immune regulation of patients with colon cancer.
Objective To investigate the expression and function of chemokine receptor CCR4 in colorectal cancer. Methods Totally 41 surgical specimens of primary colorectal cancer were collected as experimental group,and 30 cases with benign colorectal tumors were selected as control group. Positive rate of chemokine receptor CCR4 in colorectal cancer tissues was compared between two-step immunohistochemistry and RT-PCR. Relationship between chemokine receptor CCR4 and clinicopathological factors was compared by detection of two-step immunohistochemistry or RT-PCR. Results The proportion of positive patients detected by immunohistochemistry in the experimental group was significantly higher than that detected by immunohistochemistry in the control group(P < 0. 05). The proportion of positive patients detected by RT-PCR in the experimental group was significantly higher than that detected by RT-PCR in the control group(P < 0. 05). The gray scale ratio of PCR bands in the experimental group was significantly higher than that in the control group(P < 0. 05). The expressions of CCR4 in colon cancer tissues showed no significant differences in gender,age,degree of differentiation,lymph node metastasis,liver metastasis,location and other clinicopathological factors(P > 0. 05). There was significant difference in CCR4 positive expression in different Duke stages in colon cancer tissues(P < 0. 05). Conclusion Pathological examination can indicate the Duke stage of the patients. CCR4 plays an important role in immune regulation of patients with colon cancer.
引文
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[17]张霄鹏,胡志娟,孟爱宏,等.趋化因子CCL20及其受体CCR6在肺腺癌组织中的表达及与复发转移的关系研究[J].中国全科医学,2016,19(25):3065-3068.
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[19] Morichika K,Tomoyose T,Hanashiro T,et al. Recurrence of Psoriasis Vulgaris Accompanied by Treatment with C-C Chemokine Receptor Type 4(CCR4)Antibody(Mogamulizumab)Therapies in a Patient with Adult T cell Leukemia/Lymphoma:Insight into Autoinflammatory Diseases[J]. Intern Med,2016,55:1345-1349.
[20] Miah A H,Champigny A C,Graves R H,et al. Identification of pyrazolopyrimidine arylsulfonamides as CC-chemokine receptor 4(CCR4)antagonists[J]. Bioorganic&Medicinal Chemistry,2017,25(20):5327-5340.
[2] L9froos A B,Kadivar M,Lindehammer S R,et al. Colorectal cancer-infiltrating T lymphocytes display a distinct chemokine receptor expression profile[J]. European Journal of Medical Research,2017,22(1):40-49.
[3] Ou B,Zhao J,Guan S,et al. CCR4 promotes metastasis via ERK/NF-κB/MMP13 pathway and acts downstream of TNF-αin colorectal cancer[J]. Oncotarget,2016,7(30):47637-47649.
[4] Sugata K,Yasunaga J,Kinosada H,et al. HTLV-1 Viral Factor HBZ Induces CCR4 to Promote T-cell Migration and Proliferation[J]. Cancer Research,2016,76(17):5068-5077.
[5] Gonzálezarriagada W A,Lozanoburgos C,Zú1igamoreta R,et al. Clinicopathological significance of chemokine receptor(CCR1,CCR3,CCR4,CCR5,CCR7 and CXCR4)expression in head and neck squamous cell carcinomas[J]. Journal of oral pathology&medicine:official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology,2018,47(8):755-763.
[6] Cheng X,Wu H,Jin Z J,et al. Up-regulation of chemokine receptor CCR4 is associated with Human Hepatocellular Carcinoma malignant behavior[J]. Scientific Reports,2017,7(1):12362-12369.
[7] Lintermans L L,Rutgers A,Stegeman C A,et al. Chemokine receptor co-expression reveals aberrantly distributed TH effector memory cells in GPA patients[J]. Arthritis Research&Therapy,2017,19(1):136-145.
[8]杨励,牛妍艳,常瑛,等. Tregs细胞CCR4的表达变化在复发性生殖器疱疹患者发病中的意义[J].中国皮肤性病学杂志,2017(12):1297-1300.
[9]罗强,金真伊,陈少华,等. TRGV及预后相关趋化因子/受体基因在T细胞淋巴瘤中的表达变化[J].细胞与分子免疫学杂志,2017,33(3):362-366.
[10]欧长波,王秋霞,张艳红,等. IBDV感染对T细胞趋化因子受体及其配体基因表达的影响[J].中国兽医科学,2017(2):222-226.
[11]杨永红,罗静,袁军,等.刀豆蛋白A对CD4+CD25+调节性T细胞CCR4和CCR6表达的影响[J].山东医药,2016,56(32):38-40.
[12]刘高勤,肖艳辉,陈志刚,等.小鼠角膜新生血管内皮细胞的分离培养及其趋化因子受体的表达[J].中华实验眼科杂志,2016,34(2):132-136.
[13]崔丰和,黄江平,周前,等. CXC趋化因子受体5及其配体CXCL13在非小细胞肺癌中的表达及意义[J].广东医学,2016,37(16):2416-2419.
[14]涂力,蒋燚,张驰,等.趋化因子受体CCR7在人胃癌组织中的表达及其与胃癌转移的关系[J].安徽医科大学学报,2017,52(10):1472-1475.
[15]寇敬,谌天娇,邵红伟,等.人趋化因子CCL17和CCL22对CD4及CD8 T淋巴细胞亚群的趋化能力比较研究[J].免疫学杂志,2016(9):737-742.
[16]景周宏,曹勇,熊忠讯,等.趋化因子受体D6、DARC在人乳腺癌组织中的表达研究[J].重庆医学,2016,45(14):1915-1917.
[17]张霄鹏,胡志娟,孟爱宏,等.趋化因子CCL20及其受体CCR6在肺腺癌组织中的表达及与复发转移的关系研究[J].中国全科医学,2016,19(25):3065-3068.
[18] Perera L P,Zhang M,Nakagawa M,et al. Chimeric antigen receptor modified T cells that target chemokine receptor CCR4as a therapeutic modality for T-cell malignancies[J]. American Journal of Hematology,2017,92(9):892-901.
[19] Morichika K,Tomoyose T,Hanashiro T,et al. Recurrence of Psoriasis Vulgaris Accompanied by Treatment with C-C Chemokine Receptor Type 4(CCR4)Antibody(Mogamulizumab)Therapies in a Patient with Adult T cell Leukemia/Lymphoma:Insight into Autoinflammatory Diseases[J]. Intern Med,2016,55:1345-1349.
[20] Miah A H,Champigny A C,Graves R H,et al. Identification of pyrazolopyrimidine arylsulfonamides as CC-chemokine receptor 4(CCR4)antagonists[J]. Bioorganic&Medicinal Chemistry,2017,25(20):5327-5340.