CYB5D2的表达与宫颈癌患者的上皮-间质转化及生存率相关。
Expression of CYB5D2 is associated with epithelial-mesenchymal transition and survival rates in patients with cervical cancer.
作者信息
Li Dongxue, Qiu Bing, Chen Xiaohang, Hu Liang, Wen Lijuan, Wei Fengxiang
机构信息
Zunyi Medical University, Zunyi 563000, China.
Department of Gastroenterology, Heilongjiang Provincial Hospital, Harbin 150000, China.
出版信息
Transl Cancer Res. 2020 Feb;9(2):1185-1194. doi: 10.21037/tcr.2020.01.03.
BACKGROUND
CYB5D2 is a member of the membrane-associated progesterone receptors (MAPRs) family and plays essential roles in regulating nerve development. CYB5D2 is associated with tumor suppression in breast cancer. Despite the potential implication of CYB5D2 in cancer progression, its level and clinical significance in cervical cancer tissues has not been investigated yet. Via this study, we aimed to investigate the possible role played by CYB5D2 in epithelial-mesenchymal transition (EMT) in cervical cancer and correlate its level with clinical outcomes.
METHODS
The expressions of CYB5D2 and the EMT marker E-cadherin in different groups of cervical samples were compared using immunofluorescence. Furthermore, co-localization of CYB5D2 and E-cadherin was analyzed in different cervical tissue samples via confocal laser scanning microscopy. The relationship between CYB5D2/E-cadherin and the progression and clinicopathological features of cervical cancer were analyzed, and the prognostic value of CYB5D2 mRNA expression was evaluated in various tumors using the Kaplan-Meier plotter database.
RESULTS
CYB5D2 and E-cadherin were downregulated in cervical cancer (P<0.05). Co-localization of CYB5D2 and E-cadherin in cell cytoplasm in cervical cancer was apparent. The clinical and pathological information of patients with cervical cancer were analyzed, which revealed a statistically significant relationship between low CYB5D2 expression and the tumor FIGO stage (P<0.05). CYB5D2 expression was not correlated with tumors in terms of depth of myometrial invasion, patient age, histological type, and tumor grade (P>0.05). Higher expression levels of CYB5D2 mRNA were predicted to be associated with a better relapse-free survival (RFS) in patients with cervical cancer. E-cadherin expression was associated with invasive tumors, tumor grade, and FIGO stage (P<0.05) but not with patient age and histological type (P>0.05). There was a positive correlation between CYB5D2 and E-cadherin expression in cervical cancer (P<0.01).
CONCLUSIONS
These results suggest that CYB5D2 acts as a tumor suppressor in cervical cancer, inhibiting EMT by hindering E-cadherin expression.
背景
CYB5D2是膜相关孕酮受体（MAPRs）家族的成员，在调节神经发育中起重要作用。CYB5D2与乳腺癌的肿瘤抑制有关。尽管CYB5D2在癌症进展中可能具有潜在影响，但其在宫颈癌组织中的水平和临床意义尚未得到研究。通过本研究，我们旨在探讨CYB5D2在宫颈癌上皮-间质转化（EMT）中可能发挥的作用，并将其水平与临床结果相关联。
方法
使用免疫荧光比较不同组宫颈样本中CYB5D2和EMT标志物E-钙黏蛋白的表达。此外，通过共聚焦激光扫描显微镜分析不同宫颈组织样本中CYB5D2和E-钙黏蛋白的共定位。分析CYB5D2/E-钙黏蛋白与宫颈癌进展及临床病理特征之间的关系，并使用Kaplan-Meier绘图仪数据库评估CYB5D2 mRNA表达在各种肿瘤中的预后价值。
结果
CYB5D2和E-钙黏蛋白在宫颈癌中表达下调（P<0.05）。CYB5D2和E-钙黏蛋白在宫颈癌细胞质中的共定位明显。对宫颈癌患者的临床和病理信息进行分析，结果显示CYB5D2低表达与肿瘤国际妇产科联盟（FIGO）分期之间存在统计学上的显著关系（P<0.05）。CYB5D2表达与肿瘤肌层浸润深度、患者年龄、组织学类型和肿瘤分级无关（P>0.05）。预测CYB5D2 mRNA较高表达水平与宫颈癌患者更好的无复发生存期（RFS）相关。E-钙黏蛋白表达与浸润性肿瘤、肿瘤分级和FIGO分期相关（P<0.05），但与患者年龄和组织学类型无关（P>0.05）。宫颈癌中CYB5D2和E-钙黏蛋白表达之间存在正相关（P<0.01）。
结论
这些结果表明，CYB5D2在宫颈癌中起肿瘤抑制作用，通过阻碍E-钙黏蛋白表达来抑制EMT。
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