The pluripotency factor LIN28B is involved in oral carcinogenesis and associates with tumor aggressiveness and unfavorable prognosis.
The pluripotency factor LIN28B is involved in oral carcinogenesis and associates with tumor aggressiveness and unfavorable prognosis.
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DOI：
10.1186/s12935-015-0252-7
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发表时间：
2015
影响因子：
5.8
通讯作者：
Cheng J
中科院分区：
文献类型：
--
作者：
Wang D;Zhu Y;Wang Y;Li Z;Yuan C;Zhang W;Yuan H;Ye J;Yang J;Jiang H;Cheng J
LIN28B 是一种保守的 RNA 结合蛋白，与发育、细胞代谢和肿瘤发生密切相关。它经常在人类癌症中过度表达，并与肿瘤侵袭性以及不良预后相关。然而，LIN28B 在口腔鳞状细胞癌 (OSCC) 发生和进展过程中的表达模式和致癌作用尚未明确。在这里，我们试图使用化学诱导的 OSCC 动物模型、细胞系和原代标本来确定 LIN28B 的表达及其临床意义。 OSCC 动物模型是使用 7,12-二甲基-1,2-bezan-tracene (DMBA) 涂抹在仓鼠颊囊中诱导的。从不同时间点获得动物的颊部病变，并进行常规组织学分析和 LIN28B 免疫组织化学染色。通过实时 RT-PCR、蛋白质印迹和免疫荧光在一组 OSCC 细胞系中测定 LIN28B 的 mRNA、蛋白质丰度和亚细胞定位。通过免疫组织化学染色进一步评估人原发性 OSCC 样本中 LIN28B 的表达水平。此外，还评估了 LIN28B 与一些临床病理参数以及患者预后之间的关系。我们的结果显示，正常上皮细胞中常见 LIN28B 阴性或低表达，而在 DMBA 诱导的 OSCC 动物模型中，上皮发育不良和侵袭性鳞状细胞癌中发现更多的 LIN28B 丰度。在 OSCC 样本的主要部分 (39/58) 中发现了 LIN28B 的过度表达，并且与肿瘤大小 (P = 0.049) 和晚期临床分期 (P = 0.0286) 显着相关。与 LIN28B 较低的患者相比，LIN28B 较高的患者的总生存期显着降低。多变量生存分析进一步表明 LIN28B 丰度是患者总体生存的独立预后因素。我们的研究结果表明，LIN28B 与 OSCC 的发生和进展密切相关，并且在人类 OSCC 中异常过度表达。它可能代表口腔癌的一种新的诊断和预后生物标志物。
LIN28B is a conserved RNA-binding protein critically involved in development, cellular metabolism and tumorigenesis. It is frequently overexpressed in human cancers and correlates with tumor aggressiveness as well as unfavorable prognosis. However, the expression pattern and oncogenic roles of LIN28B during oral squamous cell carcinoma (OSCC) development and progression has not been well established yet. Here, we sought to determine the expression of LIN28B and its clinical significance using chemical-induced OSCC animal model, cell lines and primary specimens. The OSCC animal model was induced using 7,12-dimethyl-1,2-bezan-tracene (DMBA) painting in the hamster buccal pouch. Buccal lesions from animals were obtained from different time points and subjected to routine histological analyses and immunohistochemical staining of LIN28B. The mRNA, protein abundance and subcellular localization of LIN28B was determined in a panel of OSCC cell lines by real-time RT-PCR, western blot and immunofluorescence. The expression levels of LIN28B in human primary OSCC samples were further evaluated by immunohistochemical staining. Moreover, the relationship between LIN28B and several clinicopathological parameters as well as patients’ prognosis were also assessed. Our results revealed that negative or low LIN28B expression was commonly observed in normal epithelial, whereas more LIN28B abundance was identified in epithelial dysplasia and invasive SCC in the DMBA-induced OSCC animal model. Overexpression of LIN28B was identified in a major fraction of OSCC samples(39/58) and significantly associated with tumor size (P = 0.049) and advanced clinical stages (P = 0.0286). Patients with increased LIN28B had markedly reduced overall survival as compared to those with low LIN28B. Multivariate survival analyses further indicated that LIN28B abundance served as an independent prognostic factor for patients’ overall survival. Our findings reveal that LIN28B is critically involved in OSCC initiation and progression and aberrantly overexpressed in human OSCC. It might represent a novel diagnostic and prognostic biomarker for oral cancer.