Long-Zi Liu1, Liu-Xiao Yang1, Bo-Hao Zheng1, Ping-Ping Dong2, Xin-Yang Liu3, Zhi-Chao Wang1, Jian Zhou1, Jia Fan1, Xiao-Ying Wang1, Qiang Gao1. 1. 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. 2. Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China. 3. Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
Abstract
BACKGROUND AND OBJECTIVES: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND AND OBJECTIVES: Frequently aberrant expression of cytokeratin 7 (CK7) and cytokeratin 19 (CK19) have been observed in several humancancers. In this retrospective study, we aimed at investigating the prognostic significance of CK7 and CK19 in intrahepatic cholangiocarcinoma (ICC). METHODS: 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. RESULTS: 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. CONCLUSIONS: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.