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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

机译:癌干细胞相关标志物CD133和CD44表达在肝细胞癌中的预后价值:从患者到患者源性肿瘤异种移植模型

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摘要

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.
机译:癌症干细胞(CSC)标记物的高表达与肝细胞癌(HCC)患者的预后不良有关。但是,尚不清楚这些标记在患者源异种移植(PDX)模型中的表达以及在随后的低传代时HCC患者与其PDX模型之间这些标记的表达水平之间的关系。为了研究推定的CSC标记物在肝癌和相关PDX模型中对预后的影响,通过定量反向评估CD133,CD90,CD44,ALDH1,CK7,CK19,OCT4,SOX2,波形蛋白,巢蛋白,CD13和EpCam的表达转录-PCR(qRT-PCR),然后使用免疫组织化学方法对来自患者的肿瘤或肿瘤周围组织以及来自PDX模型的肿瘤组织进行验证。使用Kaplan-Meier方法和对数秩检验对患者和动物进行累积生存分析。通过qRT-PCR,仅CD133和CD44的表达水平在HCC患者的肿瘤组织中高于在癌周组织中。在HCC患者和PDX模型中观察到CD133 / CD44表达的预后价值具有高度一致性。 CD133和CD44的高表达水平与HCC患者的不良预后和PDX模型中的预后正相关。已提出本研究中的PDX HCC模型可预测疾病的结果,这可能为个性化药物和CSC标记物表达对预后的机制提供启示。

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