Germline PRDM1 Variant rs2185379 in Long-Term Recurrence-Free Survivors of Advanced Ovarian Cancer

Abstract

Purpose To identify the germline genetic characteristics of long-term recurrence-free survivors that can be applied to establishing a new strategy for curing advanced cancer, we investigated the whole-genome single nucleotide variants of ovarian cancer patients. Patients and Methods DNA specimens were obtained from rare long-term recurrence-free survivors with FIGO stage III–IV ovarian cancer with no recurrence for 8–23 years after primary treatments for a whole-genome analysis of approximately 660,000 single nucleotide variants. We then established a mouse model with a notable gene alteration by CRISPR/Cas9 to confirm the biological role. Results The long-term recurrence-free survivors more frequently had germline heterozygous variant rs2185379 of the PRDM1 gene exon than patients with early recurrence (6.8-fold, P=0.013) and the general population. In the mouse model, primary intraperitoneal disseminated tumors of allograft ID8 were significantly smaller in the germline heterozygous rs2185379 group than in the wild-type group (57.4% decrease, P=0.008). Immunohistochemistry showed that the area of distribution of infiltrating T lymphocytes with positive CD8 staining was significantly increased in the germline heterozygous rs2185379 group in comparison to the wild-type group. Conclusion Germline heterozygous rs2185379 in PRDM1 is correlated with an excellent prognosis and can be used to establish a new strategy for treating advanced ovarian cancer.

Screening and identification of key biomarkers associated with endometriosis using bioinformatics and next generation sequencing data analysis

“…In this investigation, we identified enriched genes in GO terms and signaling pathways that might be utilized as diagnostic and/or therapeutic targets in endometriosis. Signaling pathways include extracellular matrix organization [101], nervous system development [102], signal transduction [103], hemostasis [104], muscle contraction [105], signaling by retinoic acid [106] [189], VCAM1 [190], GRP (gastrin releasing peptide) [191], AQP8 [192], WNT6 [193], FABP4 [194], SOX6 [195], NTRK1 [196], CNTN1 [197], MMP12 [198], LAG3 [199], SOX18 [200], CCR1 [201], FLT1 [202], PRDM1 [203], TRPC3 [204], DKK2 [205], RNF157 [206], DHCR24 [207], BMP4 [208], PRL (prolactin) [209],…”

Early-Onset Ovarian Cancer <30 Years: What Do We Know about Its Genetic Predisposition?

“…Finally, we can also raise the question of whether survival differs in extremely young OC patients compared to histology-matched late-onset patients, as shown in early-onset LGSC OC patients with a less favorable prognosis and decreased 5-year survival [22]. Isolated studies point to some predictive markers associated with better survival in ovarian cancer patients, such as PRDM1 variant rs2185379, which is suggested to be positively associated with the long-term recurrence-free survival of advanced OC [143]. On the other hand, the EXO1 variant rs851797 was negatively associated with progression-free and overall survival in OC patients [144].…”