Long Houyong, Guo Xingjun, Qiao Shen, Huang Qingxing
Department of Hepatobiliary Surgery, Jining NO.1 People's Hospital, 6 Health Street, Jining, Shandong Province, 272011, China.
Department of Hepatobiliary Surgery, Dongying People's Hospital, Dongying, Shandong Province, 257091, China.
Pathol Oncol Res. 2018 Apr;24(2):339-344. doi: 10.1007/s12253-017-0249-8. Epub 2017 May 16.
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 (NFκB), 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-κB, MMP2, MMP9 and invasive ability than normal cell line, which are suppressed by LXR activation via NFκB 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.
肝X受体（LXR）激活具有抗肿瘤作用。然而，肿瘤LXR表达在肝细胞癌（HCC）患者中是否具有预后意义尚未得到探讨。从169例行常规根治性手术治疗的患者中获取原发性肝癌及癌旁非肿瘤组织。对所有患者进行预后分析。采用免疫组织化学分析法检测肿瘤LXR。在体外研究中，培养几种肝癌细胞系以检测LXR及其他细胞因子，包括核因子κB（NFκB）、基质金属蛋白酶2和9（MMP - 2和 - 9）的细胞蛋白。同时，检测培养的肝癌细胞系的侵袭能力。我们发现肿瘤样本中LXR的表达状态与HCC患者的临床特征，如肿瘤分期和转移相关。预后分析表明，肿瘤LXR表达状态与接受手术治疗的HCC患者的术后结局密切相关。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。我们的体外数据显示，肝癌细胞系的NF - κB、MMP2、MMP9水平及侵袭能力均高于正常细胞系，而LXR通过NFκB途径激活可抑制这些指标。我们的数据表明，LXR可作为HCC预后的生物标志物。有必要进一步研究探索LXR调节肿瘤行为的分子机制。
