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

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.