TTLL12在肝门部胆管癌中的表达及临床意义

The expression and clinical significance of TTLL12 in hilar cholangiocarcinoma

目的分析肝门部胆管癌及癌旁组织中微管蛋白酪氨酸连接酶类似物12(TTLL12)的表达,并探讨其与肝门部胆管癌患者临床病理特征和预后之间的关系。方法收集青岛市市立医院2016年1月至2020年12月45例肝门部胆管癌患者术后癌组织及癌旁组织制备石蜡切片,其中男性27例,女性18例,年龄(58.8±8.5)岁。采用免疫组化染色检测TTLL12和增殖细胞核抗原(Ki-67)的表达,45例患者依据癌组织TTLL12表达情况分为阴性组(n=15)和阳性组(n=30)。分析TTLL12阳性表达与淋巴结转移、肿瘤分化程度等临床病理特征的关系。采用Spearman相关分析癌组织中TTLL12与Ki-67表达的相关性。Kaplan-Meier法进行生存分析,生存率比较采用log-rank检验。结果免疫组化染色显示,45例肝门部胆管癌患者癌组织中,TTLL12与Ki-67表达明显高于癌旁组织。肝门部胆管癌患者癌组织中的TTLL12与Ki-67表达呈正相关(相关系数为0.601,P<0.001)。TTLL12、Ki-67在45例肝门部胆管癌组织中的阳性表达率分别为66.7%(30/45)、77.8%(35/45),高于癌旁组织中阳性率11.1%(5/45)、15.6%(7/45),差异具有统计学意义(χ^(2)=11.25、29.01,均P<0.001)。肝门部胆管癌患者癌组织中TTLL12、Ki-67阳性表达与淋巴结转移、肿瘤分化程度相关(均P<0.05),存在淋巴结转移和分化程度低的患者癌组织阳性表达率高。TTLL12癌组织表达阴性组中位总生存期为44个月,TTLL12阳性组中位总生存期为21个月。TTLL12癌组织表达阴性组术后5年累积生存率为33.1%,优于阳性组的18.3%,差异有统计学意义(χ^(2)=6.12,P=0.013)。结论肝门部胆管癌组织中TTLL12的表达高于癌旁组织,并且癌组织中TTLL12与Ki-67表达呈正相关。TTLL12阳性表达与肿瘤分化程度、淋巴结转移和患者不良预后密切相关。TTLL12可能成为肝门部胆管癌患者预后预测的标志物。

Objective To analyze the expression of tubulin-tyrosine ligase-like 12(TTLL12)in hilar cholangiocarcinoma and its adjacent tissues,and to explore the relationship between TTLL12 and clinicopathological features and prognosis of patients with hilar cholangiocarcinoma.Methods The carcinoma tissues and paracancerous tissues of 45 patients with hilar cholangiocarcinoma who had been operated in Qingdao Municipal Hospital from January 2016 to December 2020 were collected to prepare paraffin sections,including 27 males and 18 females,aged(58.8±8.5)years.The expression of TTLL12 and Ki-67 was detected by immunohistochemical staining.According to TTLL12 expression in cancer tissues,45 patients were divided into negative group(n=15)and positive group(n=30).The relationship between TTLL12 positive expression and clinicopathological features such as lymph node metastasis and tumor differentiation was analyzed.The correlation between TTLL12 and Ki-67 expression in cancer tissues was analyze by Spearman correlation analysis.Kaplan-Meier method was used for survival analysis,and log-rank test was used to compare the survival rate.Results Immunohistochemical staining showed that the expression of TTLL12 and Ki-67 in 45 patients with hilar cholangiocarcinoma was significantly higher than that in paracancerous tissues.The expression of TTLL12 in hilar cholangiocarcinoma was positively correlated with that of Ki-67(correlation coefficient was 0.601,P<0.001).The positive expression rates of TTLL12 and Ki-67 in 45 cases of hilar cholangiocarcinoma were 66.7%(30/45)and 77.8%(35/45),respectively,which were higher than those in adjacent tissues 11.1%(5/45)and 15.6%(7/45),and the differences were statistically significant(χ^(2)=11.25,29.01,both P<0.001).The positive expression of TTLL12 and Ki-67 in hilar cholangiocarcinoma was correlated with lymph node metastasis and tumor differentiation(all P<0.05).The median overall survival time was 44 months in TTLL12 negative group and 21 months in TTLL12 positive group.The 5-year survival rate of TTLL12 carcinoma tissue negative expression group was 33.1%,which was better than that of TTLL12 carcinoma tissue expression positive group(18.3%),and the difference was statistically significant(χ^(2)=6.12,P=0.013).Conclusions The expression of TTLL12 in hilar cholangiocarcinoma was higher than that in paracancerous tissues,and there was a positive correlation between TTLL12 and Ki-67 in carcinoma tissues.The positive expression of TTLL12 is closely related to tumor differentiation,lymph node metastasis and poor prognosis of patients.TTLL12 may be a marker for predicting the prognosis of patients with hilar cholangiocarcinoma.