Liu Long-Zi, Yang Liu-Xiao, Zheng Bo-Hao, Dong Ping-Ping, Liu Xin-Yang, Wang Zhi-Chao, Zhou Jian, Fan Jia, Wang Xiao-Ying, Gao Qiang
Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China.
Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.
J Surg Oncol. 2018 Jun;117(7):1531-1539. doi: 10.1002/jso.25027. Epub 2018 Mar 7.
Frequently aberrant expression of cytokeratin 7 (CK7) and cytokeratin 19 (CK19) have been observed in several human cancers. In this retrospective study, we aimed at investigating the prognostic significance of CK7 and CK19 in intrahepatic cholangiocarcinoma (ICC).
Immunohistochemistry was performed to assess CK7 and CK19 expression on tissue microarrays in training cohort enrolling 214 ICC patients and validation cohort comprising 108 ICC patients. Kaplan-Meier analysis, Cox's proportional hazards regression, and nomogram were applied to evaluate the prognostic significance of both CKs.
Both CK7 and CK19 expression were significantly up-regulated in ICC compared to their non-tumor counterparts, and positively correlated with aggressive tumor phenotypes, like lymph node metastasis and larger tumor size. Furthermore, high expression of either CK7 or CK19 predicted a significantly dismal postoperative survival. Integrated analysis of CK7 and CK19 expression was identified as a better indicator for survival probability. Notably, the nomogram integrating CK7/CK19 index had a perfect prognostic performance as compared with current staging systems. The results were further confirmed in the validation cohort.
CK7/CK19 index was an independent adverse prognostic factor for ICC patients' survival, and may be helpful to improve postoperative risk stratification and individualized treatment strategies.
细胞角蛋白7（CK7）和细胞角蛋白19（CK19）在多种人类癌症中常出现异常表达。在这项回顾性研究中，我们旨在探讨CK7和CK19在肝内胆管癌（ICC）中的预后意义。
采用免疫组织化学方法评估214例ICC患者的训练队列和108例ICC患者的验证队列组织芯片上CK7和CK19的表达。应用Kaplan-Meier分析、Cox比例风险回归和列线图评估这两种细胞角蛋白的预后意义。
与非肿瘤组织相比，ICC中CK7和CK19的表达均显著上调，且与侵袭性肿瘤表型呈正相关，如淋巴结转移和肿瘤体积较大。此外，CK7或CK19的高表达预示着术后生存率显著降低。CK7和CK19表达的综合分析被确定为生存概率的更好指标。值得注意的是，与目前的分期系统相比，整合CK7/CK19指数的列线图具有完美的预后性能。该结果在验证队列中得到进一步证实。
CK7/CK19指数是ICC患者生存的独立不良预后因素，可能有助于改善术后风险分层和个体化治疗策略。
