PRSS1 Upregulation Predicts Platinum Resistance in Ovarian Cancer Patients

Abstract

Ovarian cancer is the most frequent cause of death among gynecologic malignancies. A total of 80% of patients who have completed platinum-based chemotherapy suffer from relapse and develop resistance within 2 years. In the present study, we obtained patients' complete platinum (cisplatin and carboplatin) medication information from The Cancer Genome Atlas database and then divided them into two categories: resistance and sensitivity. Difference analysis was performed to screen differentially expressed genes (DEgenes) related to platinum response. Subsequently, we annotated DEgenes into the protein–protein interaction network as seed nodes and analyzed them by random walk. Finally, second-ranking protease serine 1 gene (PRSS1) was selected as a candidate gene for verification analysis. PRSS1's expression pattern was continuously studied in Oncomine and cBio Cancer Genomic Portal databases, 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. Quantitative real-time polymerase chain reaction and Western blot assay results indicated that PRSS1 expression levels in platinum-resistant samples (tissue/cell) were significantly higher than in samples sensitive to platinum. By cell transfection assay, we observed that knockdown of PRSS1 reduced the resistance of ovarian cancer cells to cisplatin. Meanwhile, 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 its key roles using multiple levels of low-throughput experiments, revealing a new treatment strategy based on a novel target factor for overcoming cisplatin resistance in ovarian cancer.

The Role of the Extracellular Matrix and Tumor-Infiltrating Immune Cells in the Prognostication of High-Grade Serous Ovarian Cancer

“…In recent work, using immunostaining and fluorescent imaging, the authors revealed that the gene PRSS1 was overexpressed in the endoplasmic reticulum of a high-grade serous ovarian cancer cell line [ 55 ]. Moreover, overexpression of this gene predicts platinum resistance in OC patients [ 56 ]. Downregulation of HMCN2 was recently associated with the inhibition of cell invasion [ 57 ].…”

Physical cell-cell interactions regulate transcriptional programmes that control the responses of high grade serous ovarian cancer patients to therapy

“…The topmost ranked genes uncovered for the PD doublets include CDCA3, PLK1, NEK2 and FAM64A (table 1) which are involved in ovarian cancer cell proliferation and drug resistance [30][31][32][33]. Furthermore, the topmost ranked genes in CR doublets included PRSS1, ECE1 and UBE2C, which promote ovarian cancer chemoresistance and progression [34][35][36]. Interestingly, MT1G, a tumour suppressor metalloprotein [37,38] was also upregulated in the CR doublets (table 1).…”