AUTHOR=Xing Linan , Tian Songyu , Mi Wanqi , Zhang Yongjian , Zhang Yunyan , Zhang Yuxi , Xu Fengye , Zhang Chunlong , Lou Ge 

TITLE=PRSS1 Upregulation Predicts Platinum Resistance in Ovarian Cancer Patients

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 8 - 2020

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.618341

DOI=10.3389/fcell.2020.618341

ISSN=2296-634X

ABSTRACT=Ovarian cancer is the most common cause of death from gynecological cancer. A large number of patients who have completed platinum-based chemotherapy will relapse and develop resistance within two years. In the present study, patients with complete platinum (cisplatin and carboplatin) medication information from TCGA were divided into two categories: resistance and sensitivity, and the difference analysis was performed. Then we annotated differentially genes into the PPI network as seed nodes for random walk analysis, and PRSS1 ranking second was selected. The expression pattern of PRSS1 was continuously studied in Oncomine and Cibioportal, revealing the key roles of PRSS1 in ovarian cancer formation. Hereafter, we conducted in-depth explorations on  PRSS1's platinum response to ovarian cancer, through tissue and cytological experiments. The RT-qPCR and western blot assays’ results indicated that PRSS1 expression levels in patients with platinum resistance were significantly higher than sensitive patients. And the consistent results were observed in the cytology test, in detail, PRSS1 was overexpression in resistant ovarian cancer cells (Skov3DDP/A2780DDP) compared with the sensitive ones (Skov3/A2780). By knocking down and over-expressing PRSS1, we observed that an increase in the ratio of Bax/Bcl-2 by knocking down PRSS1 which promoted the apoptosis ability of ovarian cancer cells. And knocking down of PRSS1 reduced the resistance of ovarian cancer cells to cisplatin, whereas overexpression of PRSS1 increased the resistance to cisplatin. In conclusion, we identified a novel risk gene PRSS1 related to ovarian cancer platinum response and confirmed the key roles of PRSS1 using multiple levels of low-throughtput experiments, which reveal a new treatment strategy based on a novel target factor for overcoming cisplatin resistance in ovarian cancer.