Research Paper|Volume 14, Issue 19|pp 7941—7958

ERAP2 as a potential biomarker for predicting gemcitabine response in patients with pancreatic cancer

Pian Yu^1,^2,^3,^4,^5,⁶, Shifu Luo⁷, Jiaxin Cai⁷, Jie Li^1,^2,^3,^4,^5,⁶, Cong Peng^1,^2,^3,^4,^5,⁶

¹The Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410000, Hunan, China
²National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Xiangya Hospital, Changsha 410000, Hunan, China
³National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha 410000, Hunan, China
⁴Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Changsha 410000, Hunan, China
⁵Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Changsha 410000, Hunan, China
⁶Xiangya Clinical Research Center for Cancer Immunotherapy, Central South University, Changsha 410000, Hunan, China
⁷Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China

* Equal contribution

Received: July 26, 2022Accepted: September 26, 2022Published: October 8, 2022

https://doi.org/10.18632/aging.204324

Copyright: © 2022 Yu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Objective: Pancreatic cancer is one of the most malignant tumors, with rapid metastasis, high mortality rate, and difficult early screening. Currently, gemcitabine is a first-line drug for pancreatic cancer patients, but its clinical effect is limited due to drug resistance. It is particularly important to further identify biomarkers associated with gemcitabine resistance to improve the sensitivity of gemcitabine treatment.

Methods: Drug sensitivity data and the corresponding transcript data derived from the Genomics of Drug Sensitivity in Cancer (GDSC) database for correlation analysis was adopted to obtain genes related to gemcitabine sensitivity. Moreover, the survival model of pancreatic cancer patients treated with gemcitabine in The Cancer Genome Atlas (TCGA) database was utilized to obtain key genes. Multiple in vitro assays were performed to verify the function of the key biomarker.

Results: Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) was identified as a biomarker promoting gemcitabine resistance, and its high expression resulted in a worse prognosis. Besides, gemcitabine significantly increased the mRNA and protein levels of ERAP2 in pancreatic cancer cells. Additionally, ERAP2 knockdown suppressed tumorigenesis and potentiated gemcitabine-induced growth, migration and invasion inhibition in human pancreatic cancer cells.

Conclusions: ERAP2 may be a novel key biomarker for gemcitabine sensitivity and diagnosis, thus providing an effective therapeutic strategy for pancreatic cancer treatment.