结直肠癌中TUBB3、CCT8表达与上皮间质转化及预后的关系  

The relationship between the expression of TUBB3,CCT8 and epithelial mesenchymal transition and prognosis in colorectal cancer

作　　者：马云云 徐斌[1] 沙巴义丁·吐尔逊[1] 王东宏[1] 刘洁[1] Ma Yunyun;Xu Bin;Sabayddin·Turson;Wang Donghong;Liu Jie(Department of Proctology,Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University,Xinjiang,Urumqi 830000,China)

机构地区：[1]新疆医科大学附属中医医院肛肠科,乌鲁木齐830000

出　　处：《疑难病杂志》2024年第9期1100-1105,共6页Chinese Journal of Difficult and Complicated Cases

基　　金：新疆少数民族科技人才特殊培养计划科研项目(2021D03016)。

摘　　要：目的探讨3型β微管蛋白(TUBB3)、含TCP-1的伴侣蛋白8(CCT8)在结直肠癌(CRC)组织中的表达及与上皮间质转化(EMT)和预后的相关性。方法回顾性选取2018年1月—2020年1月新疆医科大学附属中医医院肛肠科诊治CRC患者112例。采用实时荧光定量PCR检测癌组织和癌旁组织TUBB3、CCT8 mRNA及EMT相关指标N-钙黏素(N-cad)、E-钙黏素(E-cad)、转录因子TWIST mRNA的表达;免疫组织化学法检测TUBB3、CCT8蛋白水平;比较不同临床病理特征CRC中TUBB3、CCT8蛋白差异;Kaplan-Meier曲线及Cox回归分析TUBB3、CCT8蛋白对CRC患者预后的影响。结果CRC癌组织TUBB3、CCT8、N-cad、TWIST mRNA表达高于癌旁组织,而E-cad mRNA低于癌旁组织(t=35.030、38.353、32.172、32.405、18.928,P均<0.001);CRC癌组织中TUBB3、CCT8蛋白阳性率为91.07%(102/112)、94.64%(106/112),高于癌旁组织7.14%(8/112)、6.25%(7/112)(χ^(2)=157.836、175.032,P均<0.001);CRC中TUBB3 mRNA与CCT8 mRNA表达呈正相关(r=0.647,P<0.001),CRC中TUBB3、CCT8 mRNA表达与N-cad、TWIST mRNA表达呈正相关(r=0.667、0.621、0.703、0.686,P均<0.001),与E-cad mRNA表达呈负相关(r=-0.641、-0.587,P均<0.001);低分化、TNM分期Ⅲ期、淋巴结转移的CRC中TUBB3、CCT8 mRNA表达高于高中分化、Ⅰ~Ⅱ期、无淋巴结转移(t=20.327、20.455、21.101,15.121、14.985、15.759,P均<0.001);CRC患者3年OS TUBB3 mRNA高表达组为43.33%(26/60),低于低表达组的70.97%(44/62)(Log-rankχ^(2)=8.792,P=0.003),CCT8 mRNA高表达组患者3年OS为42.86%(27/63),低于低表达组的72.88%(43/59)(Log-rankχ^(2)=10.970,P<0.001);TUBB3、CCT8 mRNA升高及TNM分期Ⅲ期、有淋巴结转移、低分化是CRC预后的独立危险因素[HR(95%CI)=1.334(1.103~1.613),1.322(1.108~1.577),1.435(1.161~1.773),1.368(1.115~1.677),1.315(1.054~1.641)]。结论CRC中TUBB3、CCT8表达上调,两者可通过促进EMT,促进CRC的恶性进展,是新的CRC预后评估标志物。Objective To explore type 3βtubulin(TUBB3)and chaperone 8 containing TCP 1(CCT8)in colorectal cancer(CRC)and their correlation with epithelial mesenchymal transition(EMT)and prognostic significance.Methods From January 2018 to January 2020,112 patients with CRC were treated in the Department of Colorectal Surgery at the Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University were selected.Real time fluorescent quantitative PCR was used to detect TUBB3,CCT8 mRNA and EMT related indicators N cadherin(E cad),E cadherin(n cad),transcription factor twist mRNA expression.The expressions of TUBB3 and CCT8 proteins were detected by immunohistochemistry.The protein expressions of TUBB3 and CCT8 in CRC with different clinicopathological features were compared.Kaplan Meier curve and Cox regression analysis were used to analyze the effect of TUBB3 and CCT8 protein on the prognosis of CRC patients.Results The expressions of TUBB3 mRNA,CCT8 mRNA,N cad mRNA and TWIST mRNA in CRC tissues were higher than those in adjacent tissues,while E cad mRNA was lower than that in adjacent tissues(t/P=35.030,38.353,32.172,32.405,18.928,all P<0.001).The positive rates of TUBB3 and CCT8 proteins in CRC tissues were 91.07%(102/112),94.64%(106/112),which were higher than those in adjacent tissues[7.14%(8/112),6.25%(7/112)],and the difference was statistically significant(χ^(2)=157.836,175.032,P<0.001).There was a positive correlation between tubb3 mRNA and cct8 mRNA expression in CRC(r=0.647,P<0.001).The expression of TUBB3 mRNA and CCT8 mRNA in CRC was positively correlated with the expression of N-cad mRNA and TWIST mRNA(r=0.667,0.621,0.703,0.686,P<0.001),and negatively correlated with the expression of E cad mRNA(r=-0.641,-0.587,P<0.001).The expressions of TUBB3 mRNA and CCT8 mRNA in CRC with TNM stageⅢ,low differentiation and lymph node metastasis were significantly higher than those in CRC with stageⅠ~Ⅱ,high differentiation and no lymph node metastasis(t/P=20.327,20.455,21.101,15.121,14.985,15.759,all P<0.00

关 键 词：结直肠癌 3型β微管蛋白 含TCP-1的伴侣蛋白8 上皮间质转化 预后 

分 类 号：R735.34[医药卫生—肿瘤]