West China School of Medicine, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
Department of Breast Surgery, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu City, Sichuan Province, People's Republic of China.
Sci Rep. 2020 Oct 20;10(1):17739. doi: 10.1038/s41598-020-74792-5.
Chromobox (CBX) family proteins control chromatin structure and gene expression. However, the functions of CBXs in cancer progression, especially breast cancer, are inadequately studied. We assessed the significance of eight CBX proteins in breast cancer. We performed immunohistochemistry and bioinformatic analysis of data from Oncomine, GEPIA Dataset, bcGenExMiner, Kaplan-Meier Plotter, and cBioPortal. We compared mRNA and protein expression levels of eight CBX proteins between breast tumor and normal tissue. The expression difference of CBX7 was the greatest, and CBX7 was downregulated in breast cancer tissues compared with normal breast tissues. The expression of CBX2 was strongly associated with tumor stage. We further analyzed the association between the eight CBX proteins and the following clinicopathological features: menopause age, estrogen receptor (ER), progesterone receptor (PR) and HER-2 receptor status, nodal status, P53 status, triple-negative status, and the Scarff-Bloom-Richardson grade (SBR) and Nottingham prognostic index (NPI). Survival analysis in the Kaplan-Meier Plotter database showed that the eight CBX proteins were significantly associated with prognosis. Moreover, CBX genes in breast cancer patients had a high net alteration frequency of 57%. There were significant co-expression correlations between the following CBX protein pairs: CBX4 positively with CBX8, CBX6 positively with CBX7, and CBX2 negatively with CBX7. We also analyzed the Gene Ontology enrichment of the CBX proteins, including biological processes, cellular components, and molecular functions. CBX 1/2/3/5/8 may be oncogenes for breast cancer, whereas CBX 6 and 7 may be tumor suppressors for breast cancer. All eight CBX proteins may be predictive for prognosis. Clinical trials are needed to confirm the significance of the eight CBX proteins in breast cancer.
染色盒(CBX)家族蛋白控制染色质结构和基因表达。然而,CBX 在癌症进展中的作用,尤其是在乳腺癌中的作用,研究不足。我们评估了 8 种 CBX 蛋白在乳腺癌中的意义。我们对 Oncomine、GEPIA 数据集、bcGenExMiner、Kaplan-Meier Plotter 和 cBioPortal 中的数据进行了免疫组织化学和生物信息学分析。我们比较了乳腺癌组织和正常组织中 8 种 CBX 蛋白的 mRNA 和蛋白表达水平。CBX7 的表达差异最大,与正常乳腺组织相比,CBX7 在乳腺癌组织中下调。CBX2 的表达与肿瘤分期强烈相关。我们进一步分析了 8 种 CBX 蛋白与以下临床病理特征之间的关联:绝经年龄、雌激素受体(ER)、孕激素受体(PR)和 HER-2 受体状态、淋巴结状态、P53 状态、三阴性状态、Scarff-Bloom-Richardson 分级(SBR)和 Nottingham 预后指数(NPI)。Kaplan-Meier Plotter 数据库中的生存分析显示,这 8 种 CBX 蛋白与预后显著相关。此外,乳腺癌患者的 CBX 基因的净改变频率高达 57%。以下 CBX 蛋白对存在显著的共表达相关性:CBX4 与 CBX8 呈正相关,CBX6 与 CBX7 呈正相关,CBX2 与 CBX7 呈负相关。我们还分析了 CBX 蛋白的基因本体论富集,包括生物学过程、细胞成分和分子功能。CBX1/2/3/5/8 可能是乳腺癌的癌基因,而 CBX6 和 7 可能是乳腺癌的肿瘤抑制基因。所有 8 种 CBX 蛋白可能对预后有预测作用。需要进行临床试验来证实这 8 种 CBX 蛋白在乳腺癌中的意义。