Yang Gang, Wang Yicheng, Xiao Jianchun, Zhao Fangyu, Qiu Jiangdong, Liu Yueze, Chen Guangyu, Cao Zhe, You Lei, Zheng Lianfang, Zhang Taiping, Zhao Yupei
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730, China.
Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
Cell Oncol (Dordr). 2021 Apr;44(2):345-355. doi: 10.1007/s13402-020-00569-7. Epub 2020 Oct 30.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human malignancies. Cell-cycle-related and expression-elevated protein in tumor (CREPT) plays an important role in the phosphorylation of RNA Pol II, and has been implicated in the development of several types of cancer. As yet, however, there have been no reports on its role in PDAC. Here, we aimed to explore the value of CREPT as a prognostic biomarker in PDAC.
CREPT expression was assessed by immunohistochemistry (IHC) on a tissue microarray containing samples from 375 PDAC patients. Kaplan-Meier and Cox regression analyses were performed to explore the independent prognostic value of CREPT expression for the disease-free survival (DFS) and overall survival (OS) of PDAC patients. A Cell Counting Kit-8 (CCK8) assay was used to determine the growth rates and gemcitabine sensitivities of PDAC cells, while a Transwell assay was used to determine the migration and invasion abilities of PDAC cells. Subcutaneous xenografts were used to explore the effect of CREPT expression on tumor growth in vivo.
We found that CREPT is highly expressed in tumor tissues and may serve as an independent prognostic biomarker for DFS and OS of PDAC patients. In vitro assays revealed that CREPT expression promotes the proliferation, migration, invasion and gemcitabine resistance of PDAC cells, and in vivo assays showed that CREPT expression knockdown led to inhibition of PDAC tumor growth.
We conclude that high CREPT expression enhances the proliferation, migration, invasion and gemcitabine resistance of PDAC cells. In addition, we conclude that CREPT may serve as an independent prognostic biomarker and therapeutic target for PDAC patients.
胰腺导管腺癌（PDAC）是最具侵袭性的人类恶性肿瘤之一。肿瘤中细胞周期相关且表达上调蛋白（CREPT）在RNA聚合酶II的磷酸化过程中起重要作用，并与多种癌症的发生发展有关。然而，目前尚无关于其在PDAC中作用的报道。在此，我们旨在探讨CREPT作为PDAC预后生物标志物的价值。
通过免疫组织化学（IHC）对包含375例PDAC患者样本的组织芯片评估CREPT表达。进行Kaplan-Meier和Cox回归分析，以探讨CREPT表达对PDAC患者无病生存期（DFS）和总生存期（OS）的独立预后价值。使用细胞计数试剂盒8（CCK8）检测法测定PDAC细胞的生长速率和吉西他滨敏感性，同时使用Transwell检测法测定PDAC细胞的迁移和侵袭能力。采用皮下异种移植模型探讨CREPT表达对体内肿瘤生长的影响。
我们发现CREPT在肿瘤组织中高表达，可能作为PDAC患者DFS和OS的独立预后生物标志物。体外实验表明，CREPT表达促进PDAC细胞的增殖、迁移、侵袭及吉西他滨耐药性，体内实验显示，敲低CREPT表达导致PDAC肿瘤生长受抑制。
我们得出结论，CREPT高表达增强了PDAC细胞的增殖、迁移、侵袭及吉西他滨耐药性。此外，我们得出结论，CREPT可能作为PDAC患者的独立预后生物标志物和治疗靶点。
