结直肠癌中K-ras基因突变与TAK1、MAP4K2蛋白表达的相关性研究
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摘要
目的分析K-ras基因突变、转化生长因子激酶1(TAK1)蛋白和MAP4K2蛋白的表达与结直肠癌临床病理特征的关系,并分析K-ras基因突变与TAK1、MAP4K2蛋白表达的相关性。方法应用DNA测序法检测76例结直肠癌样本中K-ras基因突变情况,应用免疫组化法检测样本中TAK1和MAP4K2蛋白表达情况。结果76例结直肠癌中,K-ras基因突变率为32.89%(25例),K-ras基因突变与肿瘤分化程度有关(P<0.05),与浸润深度、是否有淋巴结转移无关;TAK1阳性率为48.68%,MAP4K2阳性率为46.05%,TAK1蛋白表达和MAP4K2蛋白表达均与肿瘤分化程度、是否有淋巴结转移有关(P<0.05),与浸润深度无关。在76例结直肠癌中,K-ras基因突变与TAK1蛋白表达、MAP4K2蛋白表达均无相关性(P>0.05),TAK1蛋白表达与MAP4K2蛋白表达之间无相关性;在25例K-ras基因突变的结直肠癌中,TAK1蛋白表达与MAP4K2蛋白表达之间呈正相关(r=0.402,P<0.028)。结论 K-ras基因突变、TAK1和MAP4K2蛋白表达均与结直肠癌的肿瘤分化程度有关,与浸润深度无关;在K-ras基因突变的结直肠癌中,TAK1蛋白表达与MAP4K2蛋白表达之间呈正相关。
Objective To analyze the correlation of K-ras gene mutations with the protein expressions of transforming growth factor-βactivating kinase 1(TAK1)protein and mitogen-activated protein kinase kinase kinase kinase 2(MAP4K2)protein in colorectal cancer.Methods K-ras gene mutations were detected by DNA sequencing analysis,and the expressions of TAK1 protein and MAP4K2 protein were detected by immunohistochemical method in 76 cases of colorectal cancer tissues.Results In 76 cases of colorectal cancer tissues,the mutation rate of K-ras gene was 32.89%(25cases),and K-ras gene mutations were correlated with the degrees of cell differentiation(P<0.05).The positive rates of TAK1 protein and MAP4K2 protein were 48.68% and 46.05%,respectively.The protein expressions of TAK1 and MAP4K2were positively correlated with the degrees of cell differentiation and lymph node metastases,respectively(P<0.05).There was no correlation between K-ras gene mutation and either TAK1 protein or MAP4K2 protein expression(P>0.05).In 25 cases of colorectal cancer with K-ras mutation,the expression of TAK1 protein was positively correlated with the expression of MAP4K2 protein(P<0.05).Conclusion K-ras gene mutation,TAK1 and MAP4K2 protein expressions were related to the degree of differentiation of colorectal cancer,but not to the depth of invasion.In colorectal cancer with K-ras gene mutation,the expression of TAK1 protein was positively correlated with the expression of MAP4K2 protein.
Objective To analyze the correlation of K-ras gene mutations with the protein expressions of transforming growth factor-βactivating kinase 1(TAK1)protein and mitogen-activated protein kinase kinase kinase kinase 2(MAP4K2)protein in colorectal cancer.Methods K-ras gene mutations were detected by DNA sequencing analysis,and the expressions of TAK1 protein and MAP4K2 protein were detected by immunohistochemical method in 76 cases of colorectal cancer tissues.Results In 76 cases of colorectal cancer tissues,the mutation rate of K-ras gene was 32.89%(25cases),and K-ras gene mutations were correlated with the degrees of cell differentiation(P<0.05).The positive rates of TAK1 protein and MAP4K2 protein were 48.68% and 46.05%,respectively.The protein expressions of TAK1 and MAP4K2were positively correlated with the degrees of cell differentiation and lymph node metastases,respectively(P<0.05).There was no correlation between K-ras gene mutation and either TAK1 protein or MAP4K2 protein expression(P>0.05).In 25 cases of colorectal cancer with K-ras mutation,the expression of TAK1 protein was positively correlated with the expression of MAP4K2 protein(P<0.05).Conclusion K-ras gene mutation,TAK1 and MAP4K2 protein expressions were related to the degree of differentiation of colorectal cancer,but not to the depth of invasion.In colorectal cancer with K-ras gene mutation,the expression of TAK1 protein was positively correlated with the expression of MAP4K2 protein.
引文
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[15]DU J,WANG Y,CHEN D,et al.BAY61-3606potentiates the anti-tumor effects of TRAIL against colon cancer through up-regulating DR4and down-regulating NF-kappaB.Cancer Lett,2016,383(2):145-153.
[2]HERREROS-VILLANUEVA M,CHEN CC,YUAN SS,et al.KRAS mutations:analytical considerations.Clin Chim Acta,2014,431:211-220[2018-01-10].https://doi.org/10.1016/j.cca.2014.01.049.
[3]SINGH A,SWEENEY MF,YU M,et al.TAK1inhibition promotes apoptosis in KRAS-dependent colon cancers.Cell,2012,148(4):639-650.
[4]MCNEW KL,WHIPPLE WJ,MEHTA AK,et al.MEKand TAK1 regulate apoptosis in colon cancer cells with KRAS-dependent activation of proinflammatory signaling.Mol Cancer Res,2016,14(12):1204-1216.
[5]CHEN YR,TAN TH.The c-Jun N-terminal kinase pathway and apoptotic signaling(review).Int J Oncol,2000,16(4):651-662.
[6]KYRIAKIS JM,AVRUCH J.Mammalian MAPK signal transduction pathways activated by stress and inflammation:a10-year update.Physiol Rev,2012,92(2):689-737.
[7]LIAO WT,WANG X,XU LH,et al.Centromere protein His a novel prognostic marker for human nonsmall cell lung cancer progression and overall patient survival.Cancer,2009,115(7):1507-1517.
[8]JAUHRI M,BHATNAGAR A,GUPTA S,et al.Prevalence and coexistence of KRAS,BRAF,PIK3CA,NRAS,TP53,and APC mutations in Indian colorectal cancer patients:next-generation sequencing-based cohort study.Tumour Biol,2017,39(2):1010428317692265.
[9]LI ZZ,BAI L,WANG F,et al.Comparison of KRASmutation status between primary tumor and metastasis in Chinese colorectal cancer patients.Med Oncol,2016,33(7):71.
[10]YUNXIA Z,JUN C,GUANSHAN Z,et al.Mutations in epidermal growth factor receptor and K-ras in Chinese patients with colorectal cancer.BMC Med Genet,2010,11:34.
[11]JIANG Y,KIMCHI ET,STAVELEY-O'CARROLL KF,et al.Assessment of K-ras mutation:a step toward personalized medicine for patients with colorectal cancer.Cancer,2009,115(16):3609-3617.
[12]CHANG YS,YEH KT,CHANG TJ,et al.Fast simultaneous detection of K-RAS mutations in colorectal cancer.BMC Cancer,2009,9:179.
[13]DAHABREH IJ,TERASAWA T,CASTALDI PJ,et al.Systematic review:anti-epidermal growth factor receptor treatment effect modification by KRASmutations in advanced colorectal cancer.Ann Intern Med,2011,154(1):37-49.
[14]IVANOV VN,KEHRL JH,RONAI Z.Role of TRAF2/GCK in melanoma sensitivity to UV-induced apoptosis.Oncogene,2000,19(7):933-942.
[15]DU J,WANG Y,CHEN D,et al.BAY61-3606potentiates the anti-tumor effects of TRAIL against colon cancer through up-regulating DR4and down-regulating NF-kappaB.Cancer Lett,2016,383(2):145-153.
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