结肠癌组织中STC1的表达及其与肿瘤微环境的关系
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摘要
目的:探讨斯钙素1(STC1)在结肠癌组织中的表达,分析STC1与结肠癌预后的相关性,并探讨其与结肠癌肿瘤微环境的联系。方法:用UALCAN数据库(http://ualcan.path.uab.edu/index.html)和Oncomine数据库(https://www. oncomine.org)分析STC1在正常结肠组织及结肠癌组织中的表达水平;RT-qPCR及Western blot检测结肠癌及其癌旁组织中STC1的表达;使用OncoLnc(http://www.oncolnc.org/)分析工具评估STC1表达水平与结肠癌临床预后的相关性。氯化钴缺氧和脂多糖诱导处理结肠癌HT-29细胞,RT-qPCR和Western blot检测细胞STC1的表达水平变化;运用TIMER分析工具(https://cistrome.shinyapps.io/timer/),分析STC1与缺氧诱导因子1α(HIF1α)及免疫调节的相关性。结果:STC1在结肠癌组织中的表达水平显著高于正常结肠组织,并且STC1的高表达与结肠癌的分期和不良预后呈正相关关系(P<0.01)。在结肠癌HT-29细胞中,缺氧能够显著诱导STC1表达,STC1的表达水平与HIF1α的水平存在正相关关系;炎症模拟条件下,STC1的表达水平显著升高,STC1与炎症分子的表达和肿瘤组织中免疫细胞的浸润水平存在密切关系。结论:STC1在结肠癌组织中高表达,是结肠癌不良预后的一个重要的分子标志物,并且STC1与结肠癌肿瘤微环境,特别是与结肠癌的缺氧及免疫调节存在密切关系。
AIM: To explore the expression of stanniocalcin 1(STC1) in colorectal cancer tissues and to analyze its relationship with prognosis, further to investigate the correlation between STC1 and tumor microenvironment. METHODS: The data of the STC1 mRNA expression were accessed by the UALCAN database(http://ualcan.path.uab.edu/index.html) and Oncomine database(https://www.oncomine.org). RT-qPCR and Western blot were used to detect the expression of STC1 in the clinical samples. OncoLnc(http://www.oncolnc.org/) analytical tool was adopted to evaluate the correlation of STC1 level and the prognosis of colorectal cancer. CoCl_2 was used to establish the hypoxia status and lipopolysaccharide(LPS) was utilized to establish inflammatory condition in the colorectal cancer HT-29 cells, respectively, and then STC1 expression was examined by RT-qPCR and Western blot. RESULTS: STC1 was over-expressed in the colorectal cancer tissues, and its high expression was positively correlated with poor prognosis of the colorectal cancer patients(P<0.01). In colorectal cancer HT-29 cells, treatment of CoCl_2 up-regulated the expression of STC1. Under the condition of inflammation by stimulating with LPS, the expression of STC1 was significantly increased. In the colorectal cancer, STC1 level was positively correlated with hypoxia-inducible factor-1α or inflammatory molecules expression, and the levels of tumor-infiltrating immune cells in colorectal cancer tissue. CONCLUSION: STC1 is over-expressed in the colorectal tumor tissue, and the high level of STC1 is an important prognosis indicator for colorectal cancer. Furthermore, STC1 is closely correlated with tumor microenvironment, especially with the tumor hypoxia and tumor immune regulation of colorectal cancer.
AIM: To explore the expression of stanniocalcin 1(STC1) in colorectal cancer tissues and to analyze its relationship with prognosis, further to investigate the correlation between STC1 and tumor microenvironment. METHODS: The data of the STC1 mRNA expression were accessed by the UALCAN database(http://ualcan.path.uab.edu/index.html) and Oncomine database(https://www.oncomine.org). RT-qPCR and Western blot were used to detect the expression of STC1 in the clinical samples. OncoLnc(http://www.oncolnc.org/) analytical tool was adopted to evaluate the correlation of STC1 level and the prognosis of colorectal cancer. CoCl_2 was used to establish the hypoxia status and lipopolysaccharide(LPS) was utilized to establish inflammatory condition in the colorectal cancer HT-29 cells, respectively, and then STC1 expression was examined by RT-qPCR and Western blot. RESULTS: STC1 was over-expressed in the colorectal cancer tissues, and its high expression was positively correlated with poor prognosis of the colorectal cancer patients(P<0.01). In colorectal cancer HT-29 cells, treatment of CoCl_2 up-regulated the expression of STC1. Under the condition of inflammation by stimulating with LPS, the expression of STC1 was significantly increased. In the colorectal cancer, STC1 level was positively correlated with hypoxia-inducible factor-1α or inflammatory molecules expression, and the levels of tumor-infiltrating immune cells in colorectal cancer tissue. CONCLUSION: STC1 is over-expressed in the colorectal tumor tissue, and the high level of STC1 is an important prognosis indicator for colorectal cancer. Furthermore, STC1 is closely correlated with tumor microenvironment, especially with the tumor hypoxia and tumor immune regulation of colorectal cancer.
引文
[1] Terzif J, Grivennikov S, Karin E, et al. Inflammation and colon cancer[J]. Gastroenterology, 2010,138(6):2101-2114.
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[3] Chan KK, Leung CO, Wong CC, et al. Secretory Stanniocalcin 1 promotes metastasis of hepatocellular carcinoma through activation of JNK signaling pathway[J]. Cancer Lett, 2017, 403:330-338。
[4] Chang AC, Doherty J, Huschtscha LI, et al. STC1 expression is associated with tumor growth and metastasis in breast cancer[J]. Clin Exp Metastasis, 2015, 32(1):15-27.
[5] 李逦,王纯,卢宏达. 马钱子碱通过抑制IL-6/STAT3信号通路诱导结肠癌SW480细胞凋亡[J]. 中国病理生理杂志, 2016, 32(6):998-1003.
[6] Sch?ning JP, Monteiro M, Gu W. Drug resistance and cancer stem cells: the shared but distinct roles of hypoxia-inducible factors HIF Iαand HIF2α[J]. Exp Pharmacol Physiol, 2017, 44(2):153-161.
[7] Chandrashekar DS, Bashel B, Creighton CJ, et al. UALCAN: A portal for facilitating tumor subgroup gene expression and survival analyses[J]. Neoplasia, 2017, 19(8):649-658.
[8] Li T, Fan J, Wang B, et al. TIMER: A Web server for comprehensive analysis of tumor-infiltrating immune cells[J]. Cancer Res, 2017, 77(21):e108.
[9] Lu M, Wagner GF, Renfro JL. Stanniocalcin stimulates phosphate reabsorption by flounder renal proximal tubule in primary culture[J]. Am J Physiol, 1994, 267(2):1356-1362.
[10] Gagliardi AD, Kuo EY, Raulic S, et al. Human stanniocalcin-2 exhibits potent growth-suppressive properties in transgenic mice independently of growth hormone and IGFs[J]. Am J Physiol Endocrinol Metab, 2005, 288(1):92-105.
[11] Bai Y, Xiao Y, Dai Y, et al. Stanniocalcin 1 promotes cell proliferation via cyclin E1/cyclin-dependent kinase 2 in human prostate carcinoma[J]. Oncol Reports, 2017, 37(4):2465-2471.
[12] Guo F, Li Y, Wang J, et al. Stanniocalcin1 (STC1) inhibits cell proliferation and invasion of cervical cancer cells[J]. PLoS One, 2013, 8(1):e53989.
[13] 高明, 龚瑾, 吕永添, 等. 连环素在结肠腺癌中的异常表达及其与预后的关系[J]. 中国病理生理杂志, 2010, 26(5):928-930.
[14] Hanahan D, Coussens LM. Accessories to the crime: functions of cells recruited to the tumor microenvironment[J]. Cancer Cell, 2012, 21(3):309-322.
[15] Hongo K, Tsuno NH, Kawai K, et al. Hypoxia enhances colon cancer migration and invasion through promotion of epithelial-mesenchymal transition[J]. J Surg Res, 2013, 182(1):75-84.
[16] Lewis CE, Pollard JW. Distinct role of macrophages in different tumor microenvironments[J]. Cancer Res, 2006, 66(2):605-612.
[2] Chang AC, Janosi J, Hulsbeek M, et al. A novel human cDNA highly homologous to the fish hormone stanniocalcin[J]. Mol Cell Endocrinol, 1995, 112(2):241-247.
[3] Chan KK, Leung CO, Wong CC, et al. Secretory Stanniocalcin 1 promotes metastasis of hepatocellular carcinoma through activation of JNK signaling pathway[J]. Cancer Lett, 2017, 403:330-338。
[4] Chang AC, Doherty J, Huschtscha LI, et al. STC1 expression is associated with tumor growth and metastasis in breast cancer[J]. Clin Exp Metastasis, 2015, 32(1):15-27.
[5] 李逦,王纯,卢宏达. 马钱子碱通过抑制IL-6/STAT3信号通路诱导结肠癌SW480细胞凋亡[J]. 中国病理生理杂志, 2016, 32(6):998-1003.
[6] Sch?ning JP, Monteiro M, Gu W. Drug resistance and cancer stem cells: the shared but distinct roles of hypoxia-inducible factors HIF Iαand HIF2α[J]. Exp Pharmacol Physiol, 2017, 44(2):153-161.
[7] Chandrashekar DS, Bashel B, Creighton CJ, et al. UALCAN: A portal for facilitating tumor subgroup gene expression and survival analyses[J]. Neoplasia, 2017, 19(8):649-658.
[8] Li T, Fan J, Wang B, et al. TIMER: A Web server for comprehensive analysis of tumor-infiltrating immune cells[J]. Cancer Res, 2017, 77(21):e108.
[9] Lu M, Wagner GF, Renfro JL. Stanniocalcin stimulates phosphate reabsorption by flounder renal proximal tubule in primary culture[J]. Am J Physiol, 1994, 267(2):1356-1362.
[10] Gagliardi AD, Kuo EY, Raulic S, et al. Human stanniocalcin-2 exhibits potent growth-suppressive properties in transgenic mice independently of growth hormone and IGFs[J]. Am J Physiol Endocrinol Metab, 2005, 288(1):92-105.
[11] Bai Y, Xiao Y, Dai Y, et al. Stanniocalcin 1 promotes cell proliferation via cyclin E1/cyclin-dependent kinase 2 in human prostate carcinoma[J]. Oncol Reports, 2017, 37(4):2465-2471.
[12] Guo F, Li Y, Wang J, et al. Stanniocalcin1 (STC1) inhibits cell proliferation and invasion of cervical cancer cells[J]. PLoS One, 2013, 8(1):e53989.
[13] 高明, 龚瑾, 吕永添, 等. 连环素在结肠腺癌中的异常表达及其与预后的关系[J]. 中国病理生理杂志, 2010, 26(5):928-930.
[14] Hanahan D, Coussens LM. Accessories to the crime: functions of cells recruited to the tumor microenvironment[J]. Cancer Cell, 2012, 21(3):309-322.
[15] Hongo K, Tsuno NH, Kawai K, et al. Hypoxia enhances colon cancer migration and invasion through promotion of epithelial-mesenchymal transition[J]. J Surg Res, 2013, 182(1):75-84.
[16] Lewis CE, Pollard JW. Distinct role of macrophages in different tumor microenvironments[J]. Cancer Res, 2006, 66(2):605-612.