锌指蛋白545在结直肠癌中的表达及其临床意义
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摘要
目的探讨锌指蛋白545(ZNF545)在结直肠癌组织中的表达及临床意义。方法采用qRT-PCR法检测32对结直肠癌组织及癌旁正常组织中(来自本院行结直肠癌根治术的32例患者)ZNF545 m RNA相对表达量;进一步采用免疫组化法检测136对结直癌组织及配对癌旁正常组织(来自组织芯片)中ZNF545蛋白表达,并分析这一表达与患者临床特征及生存预后的关系。结果结直肠癌组织中ZNF545 m RNA相对表达量明显低于配对癌旁正常组织,差异有统计学意义(P<0.05)。结直肠癌组织中ZNF545蛋白低表达(免疫组化评分≤3分)率为65.4%,明显高于配对癌旁正常组织的25.7%(P<0.05);ZNF545蛋白低表达与患者肿瘤直径、浸润深度、TNM分期相关(均P<0.05),与患者性别、年龄、肿瘤位置、分化程度、淋巴结转移无关(均P>0.05)。Kaplan-Meier生存分析结果显示,与ZNF545蛋白高表达的结直肠癌患者比较,ZNF545蛋白低表达患者的5年生存率明显降低,差异有统计学意义(P<0.05)。结论 ZNF545在结直肠癌组织中呈低表达,与患者肿瘤直径、浸润深度、TNM分期及生存预后有关。
Objective To investigate the expression of zinc finger protein 545(ZNF545) in colorectal cancer tissues and its clinical significance.Methods Quantitative reverse transcription-polymerase chain reaction(qRT-PCR) was performed to examine the expression level of ZNF545 m RNA in colorectal cancer tissues and corresponding normal tissues from 32 patients with colorectal cancer Immunohistochemical staining was also performed with tissue chips to detect the expression of ZNF545 protein in 136 pairs of colorectal cancer tissues and corresponding normal tissues.The relationship of ZNF545 protein expression with the clinical characteristics and prognosis were analyzed.Results The relative expression of ZNF545 m RNA in colorectal cancer tissues was significantly lower than that in adjacent normal tissues(P<0.05).Immunohistochemical staining of tissue chip revealed that the low expression rate of ZNF545 protein in colorectal cancer tissues was 65.4%,which was significantly higher than that in the adjacent normal tissues(25.7%,P <0.05).The low expression of ZNF545 protein was significantly correlated with tumor size,invasion depth and TNM stage(P<0.05),while not correlated with gender,age,tumor location,differentiation and lymph node metastasis(P >0.05).Kaplan-Meier survival analysis showed that the 5-year survival rate of colorectal patients with low expression of ZNF545 protein was significantly lower than that with high expression of ZNF545 protein(P<0.05).Conclusion The low expression of ZNF545 in colorectal cancer tissues is significantly associated with tumor size,invasion depth,TNM stage and poorer prognosis of colorectal cancer patients.
Objective To investigate the expression of zinc finger protein 545(ZNF545) in colorectal cancer tissues and its clinical significance.Methods Quantitative reverse transcription-polymerase chain reaction(qRT-PCR) was performed to examine the expression level of ZNF545 m RNA in colorectal cancer tissues and corresponding normal tissues from 32 patients with colorectal cancer Immunohistochemical staining was also performed with tissue chips to detect the expression of ZNF545 protein in 136 pairs of colorectal cancer tissues and corresponding normal tissues.The relationship of ZNF545 protein expression with the clinical characteristics and prognosis were analyzed.Results The relative expression of ZNF545 m RNA in colorectal cancer tissues was significantly lower than that in adjacent normal tissues(P<0.05).Immunohistochemical staining of tissue chip revealed that the low expression rate of ZNF545 protein in colorectal cancer tissues was 65.4%,which was significantly higher than that in the adjacent normal tissues(25.7%,P <0.05).The low expression of ZNF545 protein was significantly correlated with tumor size,invasion depth and TNM stage(P<0.05),while not correlated with gender,age,tumor location,differentiation and lymph node metastasis(P >0.05).Kaplan-Meier survival analysis showed that the 5-year survival rate of colorectal patients with low expression of ZNF545 protein was significantly lower than that with high expression of ZNF545 protein(P<0.05).Conclusion The low expression of ZNF545 in colorectal cancer tissues is significantly associated with tumor size,invasion depth,TNM stage and poorer prognosis of colorectal cancer patients.
引文
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[12]Wang W,Cai J,Lin Y,et al.Zinc fingers function cooperatively with KRAB domain for nuclear localization of KRAB-containing zinc finger proteins[J].PloS one,2014,9(3):e92155.DOI:10.1371/journal.pone.0092155.
[13]Zhang C,Xiang T,Li S,et al.The novel 19q13 KRAB zinc-finger tumour suppressor ZNF382 is frequently methylated in oesophageal squamous cell carcinoma and antagonises Wnt/betacatenin signalling[J].Cell death&disease,2018,9(5):573.DOI:10.1038/s41419-018-0604-z.
[2]Xiang S,Xiang T,Xiao Q,et al.Zinc-finger protein 545 is inactivated due to promoter methylation and functions as a tumor suppressor through the Wnt/beta-catenin,PI3K/AKT and MAPK/ERK signaling pathways in colorectal cancer[J].International journal of oncology,2017,51(3):801-811.DOI:10.3892/ijo.2017.4064.
[3]Deng J,Liang H,Ying G,et al.Poor survival is associated with the methylated degree of zinc-finger protein 545(ZNF545)DNA promoter in gastric cancer[J].Oncotarget,2015,6(6):4482-4495.DOI:10.18632/oncotarget.2916.
[4]WANG S,CHENG Y,DU W,et al.Zinc-finger protein 545 is a novel tumour suppressor that acts by inhibiting ribosomal RNA transcription in gastric cancer[J].Gut,2013,62(6):833-841.DOI:10.1136/gutjnl-2011-301776.
[5]Yu J,Li X,Tao Q,et al.Hypermethylation of ZNF545 is associated with poor prognosis in patients with early-stage hepatocellular carcinoma after thermal ablation[J].Gut,2015,64(11):1836-1837.DOI:10.1136/gutjnl-2015-310258.
[6]Yang W,Yang S,Zhang M,et al.ZNF545 suppresses human hepatocellular carcinoma growth by inhibiting NF-κB signaling[J].Genes&cancer,2017,8(3-4):528-535.DOI:10.18632/genesandcancer.137.
[7]Xiao Y,Xiang T,Luo X,et al.Zinc-finger protein 545 inhibits cell proliferation as a tumor suppressor through inducing apoptosis and is disrupted by promoter methylation in breast cancer[J].PloS one,2014,9(10):e110990.DOI:10.1371/journal.pone.0110990.
[8]Fan Y,Zhan Q,Xu H,et al.Epigenetic identification of ZNF545 as a functional tumor suppressor in multiple myeloma via activation of p53signaling pathway[J].Biochemical and biophysical research communications,2016,474(4):660-666.DOI:10.1016/j.bbrc.2016.04.146.
[9]Siegel R,Ma J,Zou Z,et al.Cancer statistics,2014[J].CA:a cancer journal for clinicians,2014,64(1):9-29.DOI:10.3322/caac.21208.
[10]Chen W,Zheng R,Baade PD,et al.Cancer statistics in China,2015[J].CA:a cancer journal for clinicians,2016,66(2):115-132.DOI:10.3322/caac.21338.
[11]Mathonnet M,Perraud A,Christou N,et al.Hallmarks in colorectal cancer:angiogenesis and cancer stem-like cells[J].World jo urnal of gastroenterology,2014,20(15):4189-4196.DOI:10.3748/wjg.v20.i15.4189.
[12]Wang W,Cai J,Lin Y,et al.Zinc fingers function cooperatively with KRAB domain for nuclear localization of KRAB-containing zinc finger proteins[J].PloS one,2014,9(3):e92155.DOI:10.1371/journal.pone.0092155.
[13]Zhang C,Xiang T,Li S,et al.The novel 19q13 KRAB zinc-finger tumour suppressor ZNF382 is frequently methylated in oesophageal squamous cell carcinoma and antagonises Wnt/betacatenin signalling[J].Cell death&disease,2018,9(5):573.DOI:10.1038/s41419-018-0604-z.