Down-regulation of the tumour suppressor κ-opioid receptor predicts poor prognosis in hepatocellular carcinoma patients.

Down-regulation of the tumour suppressor κ-opioid receptor predicts poor prognosis in hepatocellular carcinoma patients.
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肿瘤抑制因子κ阿片受体的下调预示着肝细胞癌患者的不良预后

DOI:
10.1186/s12885-017-3541-9
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发表时间:
2017-08-18
期刊:
影响因子:
3.8
通讯作者:
Zeng W
Zeng W
中科院分区:
医学2区
文献类型:
--
作者:
Chen D;Chen Y;Yan Y;Pan J;Xing W;Li Q;Zeng W

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阿片受体越来越多地参与癌症进展和长期患者结局。然而,κ-阿片受体(KOR)在肝细胞癌(HCC)中的表达及其意义尚不清楚。在这项研究中,KOR mRNA的表达进行了分析,在64对肝癌肿瘤组织和邻近的非肿瘤组织,KOR蛋白表达进行了分析,在174例肝癌患者的免疫组化。我们研究了KOR表达与临床病理参数之间的相关性,以说明KOR表达在HCC中的潜在预后意义。79.69%(51/64)的肝癌组织中KOR mRNA表达明显下调,癌组织中KOR表达明显低于癌旁组织(P < 0.001)。ROC曲线分析显示,KOR mRNA表达的AUC为0.745,用于检测HCC患者。HCC中KOR mRNA的低表达与肿瘤大小(P = 0.015)、分化程度(P = 0.011)和TNM分期(P = 0.021)等临床病理参数相关。此外,在174例HCC患者中检测到KOR蛋白表达下调。同样,KOR蛋白阴性表达与肿瘤大小(P = 0.002)、血管浸润(P = 0.003)、分化程度(P = 0.026)和TNM分期(P = 0.030)等临床病理特征显著相关。Kaplan-Meier生存分析显示,HCC中KOR的下调提示预后不良。KOR缺陷(KORT < N)与生存率降低和复发率增加相关(P均< 0.001)。在单因素和多因素生存分析中,KOR被确定为总生存期(OS,均P < 0.001)和无复发生存期(RFS,均P < 0.001)的一个有希望的独立危险因素。KOR在肝癌组织中的表达下调与预后不良密切相关,KOR可能是一种潜在的肿瘤抑制因子。本文的在线版本(doi:10.1186/s12885-017-3541-9)包含补充材料,可供授权用户使用。
Opioid receptors have become increasingly implicated in cancer progression and long-term patient outcomes. However, the expression and significance of the κ-opioid receptor (KOR) in hepatocellular carcinoma (HCC) remain unclear. In this study, KOR mRNA expression was analysed by real-time quantitative PCR in 64 pairs of HCC tumour tissues and adjacent non-tumour tissues, and KOR protein expression was analysed by immunohistochemistry in 174 HCC patients. We investigated the correlation between KOR expression and clinicopathological parameters to illustrate the potential prognostic significance of KOR expression in HCC. KOR mRNA expression was significantly down-regulated in 79.69% (51 of 64) of the HCC tumour samples, and KOR expression in tumour tissue was significantly lower than that in adjacent non-tumour tissues (P < 0.001). ROC curve analysis showed that KOR mRNA expression yielded AUC of 0.745, for the detection of HCC patients. Low KOR mRNA expression in HCC was correlated with aggressive clinicopathological parameters, such as tumour size (P = 0.015), differentiation grade (P = 0.011), and TNM stage (P = 0.021). Moreover, down-regulation of KOR protein expression in HCC tissues was detected in 174 HCC patients. Similarly, negative KOR protein expression was significantly correlated with aggressive clinicopathological features, such as tumour size (P = 0.002), vascular invasion (P = 0.003), differentiation grade (P = 0.026), and TNM stage (P = 0.030). Furthermore, Kaplan-Meier survival analysis demonstrated that down-regulation of KOR in HCC indicated poor prognosis. KOR deficiency (KORT < N) was correlated to a shorter survival rate and an increased recurrence (both P < 0.001). In univariate and multivariate survival analyses, KOR was identified as a promising independent risk factor for both overall survival (OS, both P < 0.001) and recurrence-free survival (RFS, both P < 0.001). Down-regulation of KOR in HCC tumour tissues has a strong association with poor prognosis and KOR might be a potential tumour suppressor. The online version of this article (doi:10.1186/s12885-017-3541-9) contains supplementary material, which is available to authorized users.
κ阿片受体激动剂对非小细胞肺癌(NSCLC)细胞生长的影响。
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发表时间: 2012-03-13
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