Beclin-1 和 LC3 的异常表达与下咽鳞癌患者的不良预后相关。
Aberrant expression of Beclin-1 and LC3 correlates with poor prognosis of human hypopharyngeal squamous cell carcinoma.
机构信息
Department of Otolaryngology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
出版信息
PLoS One. 2013 Jul 25;8(7):e69038. doi: 10.1371/journal.pone.0069038. Print 2013.
BACKGROUND
Beclin-1, a key regulator of autophagy. Microtubule-associated protein 1 light chain 3 (LC3), is involved in autophagsome formation during autophagy. The autophagic genes beclin-1 and LC3 paly an important role in the development and progression of tumor. This study was designed to investigate the expression of beclin-1 and LC3 and to clarify their clinical significance in hypopharyngeal squamous cell carcinoma (HSCC).
METHODS
Eighty-two surgical hypopharyngeal squamous cell carcinoma specimens and fifty-four adjacent non-cancerous mucosal epithelial tissues were obtained. Beclin-1 and LC3-II expression was examined by immunohistochemistry, real-time RT-PCR and Western blotting assays. Correlations with patient clinical characteristics and overall survival were evaluated.
RESULTS
Beclin-1 was positively expressed in 42.7% (35/82) of HSCC specimens (adjacent non-cancerous tissues, 79.6%, 43/54; P<0.0001). Furthermore, 41.5% (34/82) of HSCC specimens exhibited high LC3 immunoreactivity (adjacent non-cancerous tissues, 74.1%, 40/54; P=0.0002). Beclin-1 and LC3-II mRNA transcript levels were significantly lower in HSCCs than in paired non-cancerous tissues (P<0.0001, P=0.0001, respectively). Similarly, western blotting assays showed that beclin-1 and LC3-II were markedly decreased in HSCCs (P=0.02, P=0.004, respectively). A positive correlation was observed between the mRNA transcript levels of beclin-1 and LC3-II in HSCCs (r=0.51, P<0.0001; 95%CI: 0.273 to 0.689). Beclin-1 and LC3 expression were significantly correlated with T categories, differentiation and lymph node metastasis. Negative beclin-1 immunoreactivity and low LC3 expression were associated with poorer overall survival in HSCC patients (P<0.0001, P=0.0145, respectively). Multivariate analysis revealed that beclin-1 was an independent prognositic factor for overall survival.
CONCLUSION
Beclin-1 and LC3-II are downregulated in HSCCs and their aberrant expression correlates with poor prognosis of HSCCs.
背景
Beclin-1 是自噬的关键调节因子。微管相关蛋白 1 轻链 3（LC3）参与自噬体的形成。自噬基因 beclin-1 和 LC3 在肿瘤的发生和发展中发挥重要作用。本研究旨在探讨 beclin-1 和 LC3 的表达，并阐明其在下咽鳞状细胞癌（HSCC）中的临床意义。
方法
收集 82 例下咽鳞状细胞癌手术标本和 54 例相邻非癌性黏膜上皮组织。采用免疫组织化学、实时 RT-PCR 和 Western blot 检测 beclin-1 和 LC3-II 的表达。评估与患者临床特征和总生存期的相关性。
结果
Beclin-1 在 42.7%（35/82）的 HSCC 标本中呈阳性表达（相邻非癌组织为 79.6%，43/54；P<0.0001）。此外，41.5%（34/82）的 HSCC 标本中 LC3 免疫反应性较高（相邻非癌组织为 74.1%，40/54；P=0.0002）。HSCC 中的 beclin-1 和 LC3-II mRNA 转录水平明显低于配对的非癌组织（P<0.0001，P=0.0001）。同样，Western blot 检测显示 HSCC 中 beclin-1 和 LC3-II 明显减少（P=0.02，P=0.004）。HSCC 中 beclin-1 和 LC3-II 的 mRNA 转录水平呈正相关（r=0.51，P<0.0001；95%CI：0.273 至 0.689）。Beclin-1 和 LC3 的表达与 T 分期、分化和淋巴结转移显著相关。HSCC 患者中，beclin-1 免疫反应性阴性和 LC3 表达水平低与总生存期较差相关（P<0.0001，P=0.0145）。多因素分析显示，beclin-1 是总生存期的独立预后因素。
结论
Beclin-1 和 LC3-II 在 HSCC 中下调，其异常表达与 HSCC 的不良预后相关。
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