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

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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.

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.

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Abbreviations

CCK8:

Cell Counting Kit-8

CES:

composite expression score

CI:

confidence interval

CREPT:

cell-cycle-related and expression-elevated protein in tumor

CTD:

C-terminal domain

DFS:

disease-free survival

HE:

Hematoxylin-eosin

IHC:

immunohistochemistry

OS:

overall survival

PDAC:

pancreatic ductal adenocarcinoma

RPRD1B:

regulation of the nuclear precursor RNA domain containing 1B

SDS-PAGE:

SDS-polyacrylamide gel electrophoresis

TMA:

tissue microarray

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Funding

This study was supported by grants from the National Natural Science Foundation of China (No. 81772639, No. 81802475, No. 81972258, No. 81974376), the Natural Science Foundation of Beijing (No. 7192157), the CAMS Innovation Fund for Medical Sciences (CIFMS) (No.2016-I2M-1-001) and the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences (No. 2018PT32014).

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Author notes

  1. Gang Yang, Yicheng Wang and Jianchun Xiao contributed equally to this work.

Authors and Affiliations

  1. 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

    Gang Yang, Yicheng Wang, Jianchun Xiao, Fangyu Zhao, Jiangdong Qiu, Yueze Liu, Guangyu Chen, Zhe Cao, Lei You, Taiping Zhang & Yupei Zhao

  2. Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China

    Lianfang Zheng

  3. Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China

    Taiping Zhang

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  1. Gang Yang
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  3. Jianchun Xiao
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All authors contributed equally to the writing and editing of this manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Taiping Zhang or Yupei Zhao.

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This research was approved by the Research Medical Ethics Committee of Peking Union Medical College Hospital. Informed consent was obtained from each patient.

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Yang, G., Wang, Y., Xiao, J. et al. CREPT serves as a biomarker of poor survival in pancreatic ductal adenocarcinoma. Cell Oncol. 44, 345–355 (2021). https://doi.org/10.1007/s13402-020-00569-7

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