CREPT serves as a biomarker of poor survival in pancreatic ductal adenocarcinoma

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ORIGINAL ARTICLE

CREPT serves as a biomarker of poor survival in pancreatic ductal adenocarcinoma Gang Yang 1 & Yicheng Wang 1 & Jianchun Xiao 1 & Fangyu Zhao 1 & Jiangdong Qiu 1 & Yueze Liu 1 & Guangyu Chen 1 & Zhe Cao 1 & Lei You 1 & Lianfang Zheng 2 & Taiping Zhang 1,3 & Yupei Zhao 1 Accepted: 6 October 2020 # International Society for Cellular Oncology 2020

Abstract Background 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. Methods 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. Results 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.

Gang Yang, Yicheng Wang and Jianchun Xiao contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13402-020-00569-7) contains supplementary material, which is available to authorized users. * Taiping Zhang [email protected] * Yupei Zhao [email protected] Gang Yang [email protected] Yicheng Wang [email protected] Jianchun Xiao [email protected] Fangyu Zhao [email protected] Jiangdong Qiu [email protected]

Yueze Liu [email protected] Guangyu Chen [email protected] Zhe Cao [email protected] Lei You [email protected] Lianfang Zheng [email protected] Extended author information available on the last page of the article

Yang et al.

Conclusions 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. Keywords Pancreatic ductal adenocarcinoma . CREPT . Prognostic biomarker

Abbreviations CCK8 CES CI CREPT CTD DFS HE IHC OS PDAC RPRD1B SDS-PAGE TMA

Cell Counting Kit-8 composite expression score confidence int