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ERAP2 作为预测胰腺癌患者吉西他滨反应的潜在生物标志物。

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

机构信息

The Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410000, Hunan, China.

National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Xiangya Hospital, Changsha 410000, Hunan, China.

出版信息

Aging (Albany NY). 2022 Oct 8;14(19):7941-7958. doi: 10.18632/aging.204324.

DOI:10.18632/aging.204324
PMID:36214762
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9596206/
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 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.

摘要

目的

胰腺癌是最恶性的肿瘤之一，具有转移迅速、死亡率高、早期筛查困难等特点。目前，吉西他滨是胰腺癌患者的一线药物，但由于耐药性，其临床效果有限。因此，进一步确定与吉西他滨耐药相关的生物标志物，以提高吉西他滨治疗的敏感性尤为重要。

方法

采用基因药物敏感性癌症基因组学（GDSC）数据库中的药物敏感性数据与相应的转录组数据进行相关性分析，获得与吉西他滨敏感性相关的基因。此外，还利用癌症基因组图谱（TCGA）数据库中接受吉西他滨治疗的胰腺癌患者的生存模型，获得关键基因。通过多种实验验证关键生物标志物的功能。

结果

内质网氨肽酶 2（ERAP2）被鉴定为促进吉西他滨耐药的生物标志物，其高表达导致预后更差。此外，吉西他滨显著增加了胰腺癌细胞中 ERAP2 的 mRNA 和蛋白水平。此外，ERAP2 敲低抑制了人胰腺癌细胞的肿瘤发生，并增强了吉西他滨诱导的生长、迁移和侵袭抑制作用。

结论

ERAP2 可能是吉西他滨敏感性和诊断的新关键生物标志物，为胰腺癌的治疗提供了一种有效的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247b/9596206/2b5b4ae858f1/aging-14-204324-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247b/9596206/25430e60965e/aging-14-204324-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247b/9596206/fa1e7fe5538e/aging-14-204324-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247b/9596206/1741444aa618/aging-14-204324-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247b/9596206/659d51ed8595/aging-14-204324-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247b/9596206/da5be4e9bc6c/aging-14-204324-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247b/9596206/60c65cc04eee/aging-14-204324-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247b/9596206/2b5b4ae858f1/aging-14-204324-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247b/9596206/25430e60965e/aging-14-204324-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247b/9596206/fa1e7fe5538e/aging-14-204324-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247b/9596206/1741444aa618/aging-14-204324-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247b/9596206/659d51ed8595/aging-14-204324-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247b/9596206/da5be4e9bc6c/aging-14-204324-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247b/9596206/60c65cc04eee/aging-14-204324-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247b/9596206/2b5b4ae858f1/aging-14-204324-g007.jpg

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