胃癌组织中趋化因子及其受体相关变化及作用分析
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摘要
目的:筛选胃癌组织中趋化因子及其受体的表达量变化,分析其相关作用,并挑选CXCL17验证其与胃癌的相关性。方法:应用趋化因子基因芯片技术检测胃癌组织及癌旁正常组织中各趋化因子的差异表达情况,通过生物信息学分析差异表达基因的相关作用。从中挑选出CXCL17进行验证,在癌症基因组图谱数据库中进行mRNA水平验证,并进行免疫组织化学染色进行蛋白水平验证,并分析其临床相关性。结果:基因芯片检测结果显示差异在2倍以上的基因共49个,主要与免疫应答及炎症反应等相关。而通过TCGA数据分析发现CXCL17 mRNA在胃癌肿瘤组织中表达量降低(P<0.01),CXCL17蛋白表达量在肿瘤组织中亦明显降低(P<0.05),且CXCL17表达量的下调与胃癌分化程度有关(P<0.01)。结论:通过基因芯片技术筛选胃癌微环境中相关趋化因子变化情况,并验证了CXCL17与胃癌发生发展的相关性。
Objective: In this study, to analyze correlative effect, we tried to screen for changes in expression of chemokines and their receptors in gastric cancer tissues. A chemokine, named CXCL17, was picked out in this study. Methods: The chemokine gene chip technique was used to detect the difference in expression of chemokines among gastric cancer tissues and adjacent normal tissues, and the correlations between the differentially expressed genes were analyzed by bioinformatics method. CXCL17 was selected for mRNA level and protein level verification through the cancer genome atlas(TCGA) database analysis and immunohistochemistry experiments respectively. The relationship between CXCL17 and its clinical characteristics was studied as well.Results: Gene chip analysis showed an overexpression greater than two folds in 49 genes which were mainly related to immune response and inflammation. Analysis in the TCGA database showed a significant decrease in the expression of CXCL17 in gastric cancer tumor tissues(P<0.01) compared with normal adjacent tissues, and the protein expression of CXCL17 was also decreased(P<0.05). The analysis of clinicopathological data showed that the down-regulation of CXCL17 expression was associated with the degree of tumor differentiation(P<0.01).Conclusion: Our study was to screen the changes of related chemokines in gastric cancer microenvironment by gene chip technologies and the results demonstrated that CXCL17 is associated with the development of gastric cancer.
Objective: In this study, to analyze correlative effect, we tried to screen for changes in expression of chemokines and their receptors in gastric cancer tissues. A chemokine, named CXCL17, was picked out in this study. Methods: The chemokine gene chip technique was used to detect the difference in expression of chemokines among gastric cancer tissues and adjacent normal tissues, and the correlations between the differentially expressed genes were analyzed by bioinformatics method. CXCL17 was selected for mRNA level and protein level verification through the cancer genome atlas(TCGA) database analysis and immunohistochemistry experiments respectively. The relationship between CXCL17 and its clinical characteristics was studied as well.Results: Gene chip analysis showed an overexpression greater than two folds in 49 genes which were mainly related to immune response and inflammation. Analysis in the TCGA database showed a significant decrease in the expression of CXCL17 in gastric cancer tumor tissues(P<0.01) compared with normal adjacent tissues, and the protein expression of CXCL17 was also decreased(P<0.05). The analysis of clinicopathological data showed that the down-regulation of CXCL17 expression was associated with the degree of tumor differentiation(P<0.01).Conclusion: Our study was to screen the changes of related chemokines in gastric cancer microenvironment by gene chip technologies and the results demonstrated that CXCL17 is associated with the development of gastric cancer.
引文
[1]BALKWILL F R. The chemokine system and cancer[J]. J Pathol, 2012, 226(2):148-157.
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[4]LEE W Y, WANG C J, LIN T Y, et al. CXCL17, an orphan chemokine, acts as a novel angiogenic and anti-inflammatory factor[J]. Am J Physiol Endocrinol Metab, 2013, 304(1):E32-E40.
[5]MAO Y, ZHAO Q, YIN S, et al. Genome-wide expression profiling and bioinformatics analysis of deregulated genes in human gastric cancer tissue after gastroscopy[J]. Asia Pac J Clin Oncol, 2018, 14(2):e29-e36.
[6]SATOMURA H, SASAKI K, NAKAJIMA M, et al. Can expression of CXCL12 and CXCR4 be used to predict survival of gastric cancer patients?[J]. Anticancer Res, 2014, 34(8):4051-4057.
[7]MA H Y, GAO L L, LI S C, et al. CCR7 enhances TGF-beta1-induced epithelial-mesenchymal transition and is associated with lymph node metastasis and poor overall survival in gastric cancer[J]. Oncotarget, 2015, 6(27):24348-24360.
[8]IZUMI D, ISHIMOTO T, MIYAKE K, et al. CXCL12/CXCR4 activation by cancer-associated fibroblasts promotes integrin beta 1 clustering and invasiveness in gastric cancer[J].Int J Cancer, 2016, 138(5):1207-1219.
[9]LI L, YAN J, XU J, et al. CXCL17 expression predicts poor prognosis and correlates with adverse immune infiltration in hepatocellular carcinoma[J]. PLoS One, 2014, 9(10):e110064.
[10]OHLSSON L, HAMMARSTROM M L, LINDMARK G,et al. Ectopic expression of the chemokine CXCL17 in colon cancer cells[J]. Br J Cancer, 2016, 114(6):697-703.
[11]WEINSTEIN E J, HEAD R, GRIGGS D W, et al. VCC-1, a novel chemokine, promotes tumor growth[J]. Biochem Biophys Res Commun, 2006, 350(1):74-81.
[12]HIRAOKA N, YAMAZAKI-ITOH R, INO Y, et al. CXCL17and ICAM2 are associated with a potential anti-tumor immune response in early intraepithelial stages of human pancreatic carcinogenesis[J]. Gastroenterology, 2011, 140(1):310-321.
[2]BURKHARDT A M, TAI K P, FLORES-GUITERREZ J P,et al. CXCL17 is a mucosal chemokine elevated in idiopathic pulmonary fibrosis that exhibits broad antimicrobial activity[J]. J Immunol, 2012, 188(12):6399-6406.
[3]MATSUI A, YOKOO H, NEGISHI Y, et al. CXCL17 expression by tumor cells recruits CD11b+Gr1 high F4/80-cells and promotes tumor progression[J]. PLoS One, 2012,7(8):e44080.
[4]LEE W Y, WANG C J, LIN T Y, et al. CXCL17, an orphan chemokine, acts as a novel angiogenic and anti-inflammatory factor[J]. Am J Physiol Endocrinol Metab, 2013, 304(1):E32-E40.
[5]MAO Y, ZHAO Q, YIN S, et al. Genome-wide expression profiling and bioinformatics analysis of deregulated genes in human gastric cancer tissue after gastroscopy[J]. Asia Pac J Clin Oncol, 2018, 14(2):e29-e36.
[6]SATOMURA H, SASAKI K, NAKAJIMA M, et al. Can expression of CXCL12 and CXCR4 be used to predict survival of gastric cancer patients?[J]. Anticancer Res, 2014, 34(8):4051-4057.
[7]MA H Y, GAO L L, LI S C, et al. CCR7 enhances TGF-beta1-induced epithelial-mesenchymal transition and is associated with lymph node metastasis and poor overall survival in gastric cancer[J]. Oncotarget, 2015, 6(27):24348-24360.
[8]IZUMI D, ISHIMOTO T, MIYAKE K, et al. CXCL12/CXCR4 activation by cancer-associated fibroblasts promotes integrin beta 1 clustering and invasiveness in gastric cancer[J].Int J Cancer, 2016, 138(5):1207-1219.
[9]LI L, YAN J, XU J, et al. CXCL17 expression predicts poor prognosis and correlates with adverse immune infiltration in hepatocellular carcinoma[J]. PLoS One, 2014, 9(10):e110064.
[10]OHLSSON L, HAMMARSTROM M L, LINDMARK G,et al. Ectopic expression of the chemokine CXCL17 in colon cancer cells[J]. Br J Cancer, 2016, 114(6):697-703.
[11]WEINSTEIN E J, HEAD R, GRIGGS D W, et al. VCC-1, a novel chemokine, promotes tumor growth[J]. Biochem Biophys Res Commun, 2006, 350(1):74-81.
[12]HIRAOKA N, YAMAZAKI-ITOH R, INO Y, et al. CXCL17and ICAM2 are associated with a potential anti-tumor immune response in early intraepithelial stages of human pancreatic carcinogenesis[J]. Gastroenterology, 2011, 140(1):310-321.