Tumor LXR Expression is a Prognostic Marker for Patients with Hepatocellular Carcinoma
Tumor LXR Expression is a Prognostic Marker for Patients with Hepatocellular Carcinoma
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DOI：
10.1007/s12253-017-0249-8
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发表时间：
2018-04-01
影响因子：
2.8
通讯作者：
Huang, Qingxing
中科院分区：
文献类型：
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作者：
Long, Houyong;Guo, Xingjun;Huang, Qingxing
肝脏X受体（LXR）激活发挥抗肿瘤作用。然而，肿瘤LXR表达是否具有肝细胞癌（HCC）患者的预后意义尚未得到解决。原发性肝癌和邻近的非肿瘤组织来自169例接受常规根治性手术治疗的患者。所有患者均随访并进行预后分析。免疫组化法检测肿瘤LXR。在体外研究中，培养几种HCC细胞系用于LXR和其他细胞因子的细胞蛋白检测，包括核因子κ（NF kappa B）、基质金属蛋白酶2和9（MMP-2和-9）。同时检测培养的肝癌细胞系的侵袭能力。我们发现LXR在肿瘤样本中的表达状态与HCC患者的临床特征（如肿瘤分期和转移）相关。预后分析显示，肿瘤LXR表达状态与接受手术治疗的HCC患者的术后预后密切相关。LXR低表达患者的平均5年总生存率和平均总生存期显著低于LXR高表达患者。我们的体外研究结果显示，肝癌细胞系的NF-κ B、MMP 2、MMP 9和侵袭能力较正常细胞系增加，而LXR通过NF-κ B途径激活这些细胞系并抑制其侵袭能力。我们的数据表明，LXR可以作为HCC预后的生物标志物。LXR调控肿瘤行为的分子机制有待进一步研究。
Liver X receptor (LXR) activation exerts an anti-tumor effect. However, whether the tumor LXR expression has prognostic significance in hepatocellular carcinoma (HCC) patient has not been addressed yet. Primary HCC and the adjacent non-tumor tissues were obtained from 169 patients who underwent routine curative surgical treatment. All patients were followed for prognosis analyses. Tumor LXR was detected by immunohistochemical analysis. In in vitro study, several HCC cell lines were cultured for cellular protein detection of LXR and other cytokines, including nuclear factor kappa (NF kappa B), Matrix metalloproteinases 2 and 9 (MMP-2 and -9). Meanwhile, the invasion ability of cultured HCC cell lines was performed. We found that LXR expression status in tumor samples is associated with the clinical characteristics, such as tumor stage and metastasis, of HCC patients. Prognosis analysis shows that tumor LXR expression status is closely related to the post-operative outcome in HCC patients who underwent surgical treatment. Patients with low LXR expression have a significantly lower mean 5-year overall survival rate and mean overall survival period than those with high LXR level. Our in vitro data reveal that HCC cell lines had increased NF-kappa B, MMP2, MMP9 and invasive ability than normal cell line, which are suppressed by LXR activation via NF kappa B pathway. Our data suggest that LXR could be used as a biomarker for HCC prognosis. Further study is warranted to explore the molecular mechanism under which LXR regulates tumor behaves.