C14orf166 overexpression correlates with tumor progression and poor prognosis of breast cancer

C14orf166 过表达与乳腺癌肿瘤进展和不良预后相关

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作者:Tuck-yun Cheang, Hong-Yan Zhou, Wei Chen, Bing Zhang, Liangshuai Liu, Jianyong Yang, Shenming Wang, Heping Li

Background

Chromosome 14 open reading frame 166 (C14orf166) is upregulated in various tumors, but its role in breast cancer has not been reported.

Conclusion

Our findings suggested C14orf166 could be a novel prognostic biomarker of breast cancer, it also contributes to cell proliferation by regulating G1/S transition.

Methods

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.

Results

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.

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