Cheang Tuck-yun, Zhou Hong-Yan, Chen Wei, Zhang Bing, Liu Liangshuai, Yang Jianyong, Wang Shenming, Li Heping
Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Sun Yat-sen University, 510080, Guangzhou, People's Republic of China.
Department of Neurological Intensive Care Unit, The First Affiliated Hospital of Sun Yat-sen University, 510080, Guangzhou, People's Republic of China.
J Transl Med. 2016 Feb 17;14:54. doi: 10.1186/s12967-016-0805-0.
Chromosome 14 open reading frame 166 (C14orf166) is upregulated in various tumors, but its role in breast cancer has not been reported.
Quantitative real-time PCR and western blot were used to determine C14orf166 expression in normal breast epithelial cells (NBEC), breast cancer cells, and four matched pairs of breast cancer tissues and adjacent noncancerous tissues. Using immunohistochemistry, we determined C14orf166 expression in paraffin-embedded tissues from 121 breast cancer patients. Statistical analyses were performed to examine the associations among C14or166 expression, clinicopathological parameters and prognosis outcome of breast cancer. MTT and colony formation assay were used to determine the effect of C14orf166 on cell proliferation by overexpression or knockdown of C14orf166 level.
C14orf166 was upregulated in breast cancer cell lines and tissues compared with the normal cells and adjacent normal breast tissues, high C14orf166 expression was positively with advancing clinical stage. The correlation analysis between C14orf166 expression and clinicopathological characteristics suggested C14orf166 expression was significantly correlated with clinical stages, T classification, N classification and PR expression, Kaplan-Meier curves with log rank tests showed patients with low C14orf166 expression had better survival, Cox-regression analysis suggested C14orf166 was an unfavorable prognostic factor for breast cancer patients. C14orf166 overexpression promoted breast cancer cell proliferation, whereas knockdown of C14orf166 inhibited this effect. Further analysis found C14orf166 overexpression inhibited cell cycle inhibitors P21 and P27 expression, and increased the levels of Cyclin D1 and phosphorylation of Rb, suggesting C14orf166 contributed to cell proliferation by regulating G1/S transition.
Our findings suggested C14orf166 could be a novel prognostic biomarker of breast cancer, it also contributes to cell proliferation by regulating G1/S transition.
14号染色体开放阅读框166（C14orf166）在多种肿瘤中上调，但其在乳腺癌中的作用尚未见报道。
采用定量实时PCR和蛋白质免疫印迹法检测正常乳腺上皮细胞（NBEC）、乳腺癌细胞以及4对配对的乳腺癌组织和癌旁非癌组织中C14orf166的表达。通过免疫组织化学法，我们检测了121例乳腺癌患者石蜡包埋组织中C14orf166的表达。进行统计学分析以检验C14or166表达、临床病理参数与乳腺癌预后结果之间的关联。采用MTT和集落形成试验，通过过表达或敲低C14orf166水平来确定其对细胞增殖的影响。
与正常细胞和癌旁正常乳腺组织相比，C14orf166在乳腺癌细胞系和组织中上调，C14orf166高表达与临床分期进展呈正相关。C14orf166表达与临床病理特征的相关性分析表明，C14orf166表达与临床分期、T分级、N分级和PR表达显著相关，Kaplan-Meier曲线及对数秩检验显示，C14orf166低表达患者的生存率更高，Cox回归分析表明C14orf166是乳腺癌患者的不良预后因素。C14orf166过表达促进乳腺癌细胞增殖，而敲低C14orf166则抑制这种作用。进一步分析发现，C14orf166过表达抑制细胞周期抑制剂P21和P27的表达，并增加细胞周期蛋白D1水平和Rb的磷酸化，提示C14orf166通过调节G1/S期转换促进细胞增殖。
我们的研究结果表明，C14orf166可能是一种新型的乳腺癌预后生物标志物，它也通过调节G1/S期转换促进细胞增殖。
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