Oncogenic ADAM28 induces gemcitabine resistance and predicts a poor prognosis in pancreatic cancer

作者：Wei Li, Jing‐Yun Wen, Jie Chen, Xiaokun Ma, Dong‐Hao Wu, Zhan‐Hong Chen, Jianglong Huang · 发表于：World Journal of Gastroenterology · 年份：2019 · DOI：10.3748/wjg.v25.i37.5590 · 被引用次数：53 · 研究领域：HER2/EGFR in Cancer Research、Radiopharmaceutical Chemistry and Applications、Peptidase Inhibition and Analysis

BACKGROUND: Pancreatic cancer is a major cause of cancer-related death, with a 5-year overall survival rate being below 5%. The main causes of poor prognosis in pancreatic cancer include easy metastasis, high recurrence rate, and robust drug resistance. Gemcitabine is a first-line drug for patients with unresectable pancreatic cancer. However, due to drug resistance, the clinical effect is not satisfactory. ADAM28 is reported as a tumor promoter in some cancers, but its role in pancreatic cancer and gemcitabine chemoresistance in pancreatic cancer has not been elucidated. AIM: To identify if ADAM28 can act as an important target to reverse the gemcitabine drug resistance in pancreatic cancer. METHODS: RNA-sequence analysis was applied to explore the potential targets involved in the gemcitabine of pancreatic cancer. SW1990 pancreatic cancer cells were treated with an increased dose of gemcitabine, and the mRNA levels of ADAM28 were evaluated by RT-PCR. The protein and mRNA levels of ADAM28 were confirmed in the gemcitabine resistant and parallel SW1990 cells. The ADAM28 expression was also assessed in TCGA and GEO databases, and the results were confirmed in the collected tumor and adjacent normal tissues. The overall survival (OS) rate and relapse-free survival (RFS) rate of pancreatic cancer patients with high ADAM28 level and low ADAM28 level in TCGA were evaluated with Kaplan-Meier Plotter. Furthermore, the OS rate was calculated in pancreatic cancer patients with high tu...