KIF20A在大肠癌中的表达及其临床意义
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摘要
目的:探讨驱动蛋白家族成员20A(kinesin family member 20A,KIF20A)在大肠癌的表达及其与预后的关系。方法:分析TCGA数据库文献中KIF20A在大肠癌组织及癌旁正常组织中mRNA的表达;收集2011年1月至2012年12月在河南大学淮河医院105例经术后病理学检测确诊为大肠癌的石蜡组织样本,采用免疫组织化学法检测KIF20A在大肠癌组织中的蛋白表达,并分析KIF20A与临床病理参数及预后的相关性。结果:TCGA数据库分析结果表明,KIF20A在大肠癌组织中高表达,在癌旁正常组织中表达阴性或低表达(P<0.001);免疫组织化学法检测表明KIF20A在105例大肠癌组织中的阳性及阴性表达率分别为64%(67/105)和36%(38/105),差异具有统计学意义(P<0.05)。KIF20A高表达与肿瘤浸润深度、淋巴结转移、远处转移、TNM分期有显著相关性(P<0.05)。Kaplan-Meier生存分析显示,KIF20A高表达的患者生存时间、无复发生存时间显著缩短(P<0.001)。Cox回归分析显示KIF20A是影响大肠癌患者预后的独立危险因素。结论:KIF20A在大肠癌中表达上调,其可能作为预测大肠癌患者预后的分子标志物,参与大肠癌的发生发展过程。
Objective: To explore the expression of KIF20 A(kinesin family member 20 A) in colorectal cancer(CRC) tissues and adjacent normal tissues, and to analyze the relationship between KIF20 A expression level and clinicopathological factors in CRC patients. Meth-ods: Data from The Cancer Genome Atlas(TCGA) database were used to analyze KIF20 A mRNA expression in CRC tissues and adjacent normal tissues. A total of 105 paraffin samples were obtained from CRC patients who had undergone surgery at Huai He Hospital of Henan University, from January 2011 to December 2012. Immunohistochemical staining(IHC) was performed to examine KIF20 A pro-tein expression in tumor samples for which complete clinical and pathological data were available. Statistical analyses were applied to analyze the association between KIF20 A expression and the clinical data, as well as with survival outcomes. Results: Bioinformatics analysis showed that the mRNA expression level of KIF20 A was upregulated in CRC tissues and normal tissues(P<0.001). IHC revealed significantly higher expression of KIF20 A in CRC tissues from 67 patients(64%) and lower or undetectable expression in 38 patients(36%). The difference was statistically significant(P<0.05). Overexpression of KIF20 A in CRC tissues was significantly associated with depth of invasion, lymphatic node metastasis, distant metastasis, and TNM stage(all P<0.05). Kaplan-Meier survival analysis showed that patients with high levels of KIF20 A expression had poor prognosis compared to patients with low levels of KIF20 A expression. Cox proportional hazard regression analysis revealed that KIF20 A was an independent prognostic factor in patients with CRC. Conclusions:KIF20 A is upregulated in CRC tissues and could serve as a novel prognostic biomarker for CRC patients.
Objective: To explore the expression of KIF20 A(kinesin family member 20 A) in colorectal cancer(CRC) tissues and adjacent normal tissues, and to analyze the relationship between KIF20 A expression level and clinicopathological factors in CRC patients. Meth-ods: Data from The Cancer Genome Atlas(TCGA) database were used to analyze KIF20 A mRNA expression in CRC tissues and adjacent normal tissues. A total of 105 paraffin samples were obtained from CRC patients who had undergone surgery at Huai He Hospital of Henan University, from January 2011 to December 2012. Immunohistochemical staining(IHC) was performed to examine KIF20 A pro-tein expression in tumor samples for which complete clinical and pathological data were available. Statistical analyses were applied to analyze the association between KIF20 A expression and the clinical data, as well as with survival outcomes. Results: Bioinformatics analysis showed that the mRNA expression level of KIF20 A was upregulated in CRC tissues and normal tissues(P<0.001). IHC revealed significantly higher expression of KIF20 A in CRC tissues from 67 patients(64%) and lower or undetectable expression in 38 patients(36%). The difference was statistically significant(P<0.05). Overexpression of KIF20 A in CRC tissues was significantly associated with depth of invasion, lymphatic node metastasis, distant metastasis, and TNM stage(all P<0.05). Kaplan-Meier survival analysis showed that patients with high levels of KIF20 A expression had poor prognosis compared to patients with low levels of KIF20 A expression. Cox proportional hazard regression analysis revealed that KIF20 A was an independent prognostic factor in patients with CRC. Conclusions:KIF20 A is upregulated in CRC tissues and could serve as a novel prognostic biomarker for CRC patients.
引文
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[4]Bray F,Ferlay J,Soerjomataram I,et al.Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36cancers in 185 countries[J].CA Cancer J Clin,2018,68(6):394-424.
[5]Hirokawa N,Noda Y,Okada Y.Kinesin and dynein superfamily proteins in organelle transport and cell division[J].Curr Opin Cell Biol,1998,10(1):60-73.
[6]Yamashita J,Fukushima S,Jinnin M,et al.Kinesin family member 20Ais a novel melanoma-associated antigen[J].Acta Derm Venereol,2012,92(6):593-597.
[7]Khongkow P,Gomes AR,Gong C,et al.Paclitaxel targets FOXM1 to regulate KIF20A in mitotic catastrophe and breast cancer paclitaxel resistance[J].Oncogene,2016,35(8):990-1002.
[8]Zou JX,Duan Z,Wang J,et al.Kinesin family deregulation coordinated by bromodomain protein ANCCA and histone methyltransferase MLLfor breast cancer cell growth,survival,and tamoxifen resistance[J].Mol Cancer Res,2014,12(4):539-549.
[9]Liu SL,Lin HX,Qiu F,et al.Overexpression of kinesin family member20a correlates with disease progression and poor prognosis in human nasopharyngeal cancer:A retrospective analysis of 105 patients[J].PLoS One,2017,12(1):e0169280.
[10]Taniuchi K,Furihata M,Saibara T.KIF20A-mediated RNA granule transport system promotes the invasiveness of pancreatic cancer cells[J].Neoplasia,2014,16(12):1082-1093.
[11]Imai K,Hirata S,Irie A,et al.Identification of HLA-A2-restricted CTLepitopes of a novel tumour-associated antigen,KIF20A,overexpressed in pancreatic cancer[J].Br J Cancer,2011,104(2):300-307.
[12]Stangel D,Erkan M,Buchholz M,et al.Kif20a inhibition reduces mi-gration and invasion of pancreatic cancer cells[J].J Surg Res,2015,197(1):91-100.
[13]Gasnereau I,Boissan M,Margall-Ducos G,et al.KIF20A mRNA and its product MKlp2 are increased during hepatocyte proliferation and hepatocarcinogenesis[J].Am J Pathol,2012,180(1):131-140.
[14]Zhao X,Zhou LL,Li X,et al.Overexpression of KIF20A confers malignant phenotype of lung adenocarcinoma by promoting cell proliferation and inhibiting apoptosis[J].Cancer Med,2018,7(9):4678-4689.
[15]Xiu G,Sui X,Wang Y,et al.FOXM1 regulates radiosensitivity of lung cancer cell partly by upregulating KIF20A[J].Eur J Pharmacol,2018,833:79-85.
[16]Verhey KJ,Hammond JW.Traffic control:regulation of kinesin motors[J].Nat Rev Mol Cell Biol,2009,10(11):765-777.
[17]Echard A,Jollivet F,Martinez O,et al.Interaction of a Golgi-associated kinesin-like protein with Rab6[J].Science,1998,279(5350):580-585.
[18]Yan GR,Zou FY,Dang BL,et al.Genistein-induced mitotic arrest of gastric cancer cells by downregulating KIF20A,a proteomics study[J].Proteomics,2012,12(14):2391-2399.
[19]Zhang W,He W,Shi Y,et al.High Expression of KIF20A Is associated with poor overall survival and tumor progression in early-stage cervical squamous cell carcinoma[J].PLoS One,2016,11(12):e0167449.
[2]陈万青,郑荣寿,张思维,等.2013年中国恶性肿瘤发病和死亡分析[J].中国肿瘤,2017,26(1):1-7.
[3]Siegel RL,Miller KD,Jemal A.Cancer statistics,2018[J].CA Cancer JClin,2018,68(1):7-30.
[4]Bray F,Ferlay J,Soerjomataram I,et al.Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36cancers in 185 countries[J].CA Cancer J Clin,2018,68(6):394-424.
[5]Hirokawa N,Noda Y,Okada Y.Kinesin and dynein superfamily proteins in organelle transport and cell division[J].Curr Opin Cell Biol,1998,10(1):60-73.
[6]Yamashita J,Fukushima S,Jinnin M,et al.Kinesin family member 20Ais a novel melanoma-associated antigen[J].Acta Derm Venereol,2012,92(6):593-597.
[7]Khongkow P,Gomes AR,Gong C,et al.Paclitaxel targets FOXM1 to regulate KIF20A in mitotic catastrophe and breast cancer paclitaxel resistance[J].Oncogene,2016,35(8):990-1002.
[8]Zou JX,Duan Z,Wang J,et al.Kinesin family deregulation coordinated by bromodomain protein ANCCA and histone methyltransferase MLLfor breast cancer cell growth,survival,and tamoxifen resistance[J].Mol Cancer Res,2014,12(4):539-549.
[9]Liu SL,Lin HX,Qiu F,et al.Overexpression of kinesin family member20a correlates with disease progression and poor prognosis in human nasopharyngeal cancer:A retrospective analysis of 105 patients[J].PLoS One,2017,12(1):e0169280.
[10]Taniuchi K,Furihata M,Saibara T.KIF20A-mediated RNA granule transport system promotes the invasiveness of pancreatic cancer cells[J].Neoplasia,2014,16(12):1082-1093.
[11]Imai K,Hirata S,Irie A,et al.Identification of HLA-A2-restricted CTLepitopes of a novel tumour-associated antigen,KIF20A,overexpressed in pancreatic cancer[J].Br J Cancer,2011,104(2):300-307.
[12]Stangel D,Erkan M,Buchholz M,et al.Kif20a inhibition reduces mi-gration and invasion of pancreatic cancer cells[J].J Surg Res,2015,197(1):91-100.
[13]Gasnereau I,Boissan M,Margall-Ducos G,et al.KIF20A mRNA and its product MKlp2 are increased during hepatocyte proliferation and hepatocarcinogenesis[J].Am J Pathol,2012,180(1):131-140.
[14]Zhao X,Zhou LL,Li X,et al.Overexpression of KIF20A confers malignant phenotype of lung adenocarcinoma by promoting cell proliferation and inhibiting apoptosis[J].Cancer Med,2018,7(9):4678-4689.
[15]Xiu G,Sui X,Wang Y,et al.FOXM1 regulates radiosensitivity of lung cancer cell partly by upregulating KIF20A[J].Eur J Pharmacol,2018,833:79-85.
[16]Verhey KJ,Hammond JW.Traffic control:regulation of kinesin motors[J].Nat Rev Mol Cell Biol,2009,10(11):765-777.
[17]Echard A,Jollivet F,Martinez O,et al.Interaction of a Golgi-associated kinesin-like protein with Rab6[J].Science,1998,279(5350):580-585.
[18]Yan GR,Zou FY,Dang BL,et al.Genistein-induced mitotic arrest of gastric cancer cells by downregulating KIF20A,a proteomics study[J].Proteomics,2012,12(14):2391-2399.
[19]Zhang W,He W,Shi Y,et al.High Expression of KIF20A Is associated with poor overall survival and tumor progression in early-stage cervical squamous cell carcinoma[J].PLoS One,2016,11(12):e0167449.
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