Prognostic value of the expression of cancer stem cell-related markers CD133 and CD44 in hepatocellular carcinoma: From patients to patient-derived tumor xenograft models.

// Qihong Zhao 1, * , Heng Zhou 2, * , Qifei Liu 1 , Ye Cao 1 , Gang Wang 4 , Anla Hu 1 , Liang Ruan 1 , Sufang Wang 1 , Qingli Bo 1 , Wenjun Chen 1 , Chuanlai Hu 1 , Dexiang Xu 1 , Fangbiao Tao 1 , Jiyu Cao 1 , Yongsheng Ge 5 , Zongfan Yu 6 , Li Li 1 , Hua Wang 2, 3, 7 1 Department of Food and Nutrition Hygiene, School of Public Health, Anhui Medical University, Hefei, China 2 School of Pharmacy, Anhui Medical University, Hefei, China 3 Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China 4 Department of Oncology, Affiliated Provincial Hospital of Anhui Medical University, Hefei, China 5 Department of General Surgery, Affiliated Provincial Hospital of Anhui Medical University, Hefei, China 6 Department of General Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China 7 Institute for Liver Disease, Anhui Medical University, Hefei, China * These authors contributed equally to this work Correspondence to: Li Li, email: li1964li@163.com Hua Wang, email: wanghua@ahmu.edu.cn Keywords: prognostic value, cancer stem cell markers, hepatocellular carcinoma, patient-derived tumor xenograft models Received: October 10, 2015      Accepted: June 06, 2016      Published: June 18, 2016 ABSTRACT High expression of cancer stem cell (CSC) markers is related to poor prognosis of patients with hepatocellular carcinoma (HCC). However, the expression of these markers in patient-derived xenograft (PDX) models and the relationship of the expression levels of these markers between HCC patients and their PDX models at subsequent low passages are unclear. To investigate the prognostic impact of putative CSC markers in patients with HCC and in related PDX models, the expression of CD133, CD90, CD44, ALDH1, CK7, CK19, OCT4, SOX2, vimentin, nestin, CD13 and EpCam were assessed by quantitative reverse transcription-PCR (qRT-PCR) and then were validated using immunohistochemistry in tumor or peritumoral tissues from patients and tumor tissues from PDX models. Cumulative survival analysis of the patients and animals was conducted using the Kaplan-Meier method and the log-rank test. Only the expression levels of CD133 and CD44 were higher in tumor tissues than in the peritumoral tissues of HCC patients by qRT-PCR. High consistency of the prognostic value of the expression of CD133/CD44 was observed in HCC patients and the PDX models. High expression levels of CD133 and CD44 were positively related to the poor prognosis of HCC patients and to that in the PDX models. PDX HCC models in the present study have been suggested to be predictive of disease outcome, which could shed light on personalized medicine and the mechanisms of CSC marker expression on prognosis.