Metastasis-associated in colon cancer-1(MACC1) is an oncogene that was first identified in colon cancer. The upstream and downstream of MACC1 form a delicate regulatory network that supports its tumorigenic role in ca...Metastasis-associated in colon cancer-1(MACC1) is an oncogene that was first identified in colon cancer. The upstream and downstream of MACC1 form a delicate regulatory network that supports its tumorigenic role in cancers. Multiple functions of MACC1 have been discovered in many cancers. In gastric cancer(GC), MACC1 has been shown to be involved in oncogenesis and t umor progression. MACC1 overexpression adversely affects the clinical outcomes of GC patients. Regarding the mechanism of action of MACC1 in GC, studies have shown that it promotes the epithelialto-mesenchymal transition and accelerates cancer metastasis. MACC1 is involved in many hallmarks of GC in addition to metastasis. MACC1 promotes vasculogenic mimicry(VM) via TWIST1/2, and VM increases the tumor blood supply, which is necessary for tumor progression. MACC1 also facilitates GC lymphangiogenesis by upregulating extracellular secretion of VEGF-C/D, indicating that MACC1 may be an important player in GC lymphatic dissemination. Additionally, MACC1 supports GC growth under metabolic stress by enhancing the Warburg effect. In conclusion, MACC1 participates in multiple biological processes inside and outside of GC cells, making it an important mediator of the tumor microenvironment.展开更多
AIM：To investigate the association of variations in the cyclooxygenase-2 （COX2） and uridine diphosphate glucuronosyltransferase 1A6 （UGTIA6） genes and non-steroidal anti-inflammatory drugs （NSAIDs） use with ris...AIM：To investigate the association of variations in the cyclooxygenase-2 （COX2） and uridine diphosphate glucuronosyltransferase 1A6 （UGTIA6） genes and non-steroidal anti-inflammatory drugs （NSAIDs） use with risk of colon cancer.METHODS： NSAIDs, which are known to reduce the risk of colon cancer, act directly on COX2 and reduce its activity. Epidemiological studies have associated variations in the COX2 gene with colon cancer risk, but others were unable to replicate this finding. Similarly,enzymes in the UGT1A6 gene have been demonstrated to modify the therapeutic effect of NSAIDs on colon adenomas. Polymorphisms in the UGTIA6 gene have been statistically shown to interact with NSAID intake to influence risk of developing colon adenomas, but not colon cancer. Here we examined the association of tagging single nucleotide polymorphisms （SNPs） in the COX2 and UGTIA6 genes, and their interaction with NSAID consumption, on risk of colon cancer in a population of 422 colon cancer cases and 481 population controls.RESULTS： No SNP in either gene was individually statistically significantly associated with colon cancer, nor did they statistically significantly change the protective effect of NSAID consumption in our sample. Like others, we were unable to replicate the association of variants in the COX2 gene with colon cancer risk （P 〉 0.05）,and we did not observe that these variants modify the protective effect of NSAIDs （P 〉 0.05）. We were able to confirm the lack of association of variants in UGT1A6 with colon cancer risk, although further studies will have to be conducted to confirm the association of these variants with colon adenomas.CONCLUSION： Our study does not support a role of COX2 and UGTIA6 genetic variations in the development of colon cancer.展开更多
To the Editor:Long non-coding RNAs(lncRNAs)are a class of RNA molecules comprising more than 200 nucleotides in length,which possess negligible ability to encode functional proteins.LncRNAs are involved in several cel...To the Editor:Long non-coding RNAs(lncRNAs)are a class of RNA molecules comprising more than 200 nucleotides in length,which possess negligible ability to encode functional proteins.LncRNAs are involved in several cell events,and their dysregulation has been reported to mediate tumor development and progression.Colon cancer-associated transcript 1(CCAT1)is consistently overexpressed in a range of cancer cells and tissues.Cancer treatment strategies that target CCAT1 have great potential.展开更多
目的 :分析结肠癌相关转录因子1(CCAT-1)m RNA在结直肠癌患者外周血中的表达水平与临床病理特征及预后生存的关联,探讨CCAT-1在结直肠癌早期筛查及病程预后评估中的作用。方法:采用实时定量PCR法(q PCR)检测结直肠癌(60例)、结直肠腺瘤...目的 :分析结肠癌相关转录因子1(CCAT-1)m RNA在结直肠癌患者外周血中的表达水平与临床病理特征及预后生存的关联,探讨CCAT-1在结直肠癌早期筛查及病程预后评估中的作用。方法:采用实时定量PCR法(q PCR)检测结直肠癌(60例)、结直肠腺瘤(30例)及健康志愿者(30例)外周血中CCAT-1 m RNA表达,采用ROC曲线判断CCAT-1对结直肠癌的诊断价值,计算Youden指数确定CCAT-1对结直肠癌的诊断阈值;采用双变量相关(bivariate correlation)Pearson检验分析CCAT-1m RNA表达水平与结直肠癌患者临床病理特征;采用Kaplan-Meier生存分析(Log-rank检验)分析CCAT-1 m RNA表达与结直肠癌患者3年生存率的相关性,绘制生存曲线。结果:结直肠癌患者外周血CCAT-1 m RNA水平相对于结直肠腺瘤患者(P<0.01)、健康志愿者(P<0.01)显著高表达,CCAT-1 m RNA在健康志愿者、结直肠腺瘤及结直肠癌患者外周血中的表达量呈逐渐递增趋势;结直肠癌患者外周血CCAT-1 m RNA表达量与肿瘤直径(P<0.05)、分化程度(P<0.01)、原发灶浸润深度(P<0.01)、淋巴结转移数(P<0.01)、远处转移(P<0.05)及TNM分期(P<0.05)呈显著正相关,与3年生存率呈负相关(P<0.05);CCAT-1 m RNA高表达组生存时间显著低于低表达组(P<0.01)。结论:CCAT-1可作为一种有价值的结直肠癌早期筛查及预后评估的标志物。展开更多
文摘Metastasis-associated in colon cancer-1(MACC1) is an oncogene that was first identified in colon cancer. The upstream and downstream of MACC1 form a delicate regulatory network that supports its tumorigenic role in cancers. Multiple functions of MACC1 have been discovered in many cancers. In gastric cancer(GC), MACC1 has been shown to be involved in oncogenesis and t umor progression. MACC1 overexpression adversely affects the clinical outcomes of GC patients. Regarding the mechanism of action of MACC1 in GC, studies have shown that it promotes the epithelialto-mesenchymal transition and accelerates cancer metastasis. MACC1 is involved in many hallmarks of GC in addition to metastasis. MACC1 promotes vasculogenic mimicry(VM) via TWIST1/2, and VM increases the tumor blood supply, which is necessary for tumor progression. MACC1 also facilitates GC lymphangiogenesis by upregulating extracellular secretion of VEGF-C/D, indicating that MACC1 may be an important player in GC lymphatic dissemination. Additionally, MACC1 supports GC growth under metabolic stress by enhancing the Warburg effect. In conclusion, MACC1 participates in multiple biological processes inside and outside of GC cells, making it an important mediator of the tumor microenvironment.
基金Supported by A Damon Runyon Cancer Research Foundation Clinical Investigator Award,CI-8An R25 training grant from the National Cancer Institute,R25T CA094186+1 种基金The Case Center for Transdisciplinary Research on Energetics and Cancer,1U54 CA-116867-01A National Cancer Institute K22 Award,1K22 CA120545-01
文摘AIM：To investigate the association of variations in the cyclooxygenase-2 （COX2） and uridine diphosphate glucuronosyltransferase 1A6 （UGTIA6） genes and non-steroidal anti-inflammatory drugs （NSAIDs） use with risk of colon cancer.METHODS： NSAIDs, which are known to reduce the risk of colon cancer, act directly on COX2 and reduce its activity. Epidemiological studies have associated variations in the COX2 gene with colon cancer risk, but others were unable to replicate this finding. Similarly,enzymes in the UGT1A6 gene have been demonstrated to modify the therapeutic effect of NSAIDs on colon adenomas. Polymorphisms in the UGTIA6 gene have been statistically shown to interact with NSAID intake to influence risk of developing colon adenomas, but not colon cancer. Here we examined the association of tagging single nucleotide polymorphisms （SNPs） in the COX2 and UGTIA6 genes, and their interaction with NSAID consumption, on risk of colon cancer in a population of 422 colon cancer cases and 481 population controls.RESULTS： No SNP in either gene was individually statistically significantly associated with colon cancer, nor did they statistically significantly change the protective effect of NSAID consumption in our sample. Like others, we were unable to replicate the association of variants in the COX2 gene with colon cancer risk （P 〉 0.05）,and we did not observe that these variants modify the protective effect of NSAIDs （P 〉 0.05）. We were able to confirm the lack of association of variants in UGT1A6 with colon cancer risk, although further studies will have to be conducted to confirm the association of these variants with colon adenomas.CONCLUSION： Our study does not support a role of COX2 and UGTIA6 genetic variations in the development of colon cancer.
基金supported by the grant from the National Natural Science Foundation of China(No.81972322).
文摘To the Editor:Long non-coding RNAs(lncRNAs)are a class of RNA molecules comprising more than 200 nucleotides in length,which possess negligible ability to encode functional proteins.LncRNAs are involved in several cell events,and their dysregulation has been reported to mediate tumor development and progression.Colon cancer-associated transcript 1(CCAT1)is consistently overexpressed in a range of cancer cells and tissues.Cancer treatment strategies that target CCAT1 have great potential.
文摘目的 :分析结肠癌相关转录因子1(CCAT-1)m RNA在结直肠癌患者外周血中的表达水平与临床病理特征及预后生存的关联,探讨CCAT-1在结直肠癌早期筛查及病程预后评估中的作用。方法:采用实时定量PCR法(q PCR)检测结直肠癌(60例)、结直肠腺瘤(30例)及健康志愿者(30例)外周血中CCAT-1 m RNA表达,采用ROC曲线判断CCAT-1对结直肠癌的诊断价值,计算Youden指数确定CCAT-1对结直肠癌的诊断阈值;采用双变量相关(bivariate correlation)Pearson检验分析CCAT-1m RNA表达水平与结直肠癌患者临床病理特征;采用Kaplan-Meier生存分析(Log-rank检验)分析CCAT-1 m RNA表达与结直肠癌患者3年生存率的相关性,绘制生存曲线。结果:结直肠癌患者外周血CCAT-1 m RNA水平相对于结直肠腺瘤患者(P<0.01)、健康志愿者(P<0.01)显著高表达,CCAT-1 m RNA在健康志愿者、结直肠腺瘤及结直肠癌患者外周血中的表达量呈逐渐递增趋势;结直肠癌患者外周血CCAT-1 m RNA表达量与肿瘤直径(P<0.05)、分化程度(P<0.01)、原发灶浸润深度(P<0.01)、淋巴结转移数(P<0.01)、远处转移(P<0.05)及TNM分期(P<0.05)呈显著正相关,与3年生存率呈负相关(P<0.05);CCAT-1 m RNA高表达组生存时间显著低于低表达组(P<0.01)。结论:CCAT-1可作为一种有价值的结直肠癌早期筛查及预后评估的标志物。
