The TNF receptor modulator SPATA2 is a novel predictor of outcome in ovarian cancer

Summary

Inflammation plays a crucial role in the pathogenesis of cancer with tumor necrosis factor alpha (TNFα) as a key mediator. Recently, spermatogenesis‐associated protein 2 (SPATA2) was identified as a TNF receptor modulator which is required for TNF‐induced inflammation and apoptosis. The available data on TNFα in ovarian cancer (OC) are inconsistent and SPATA2 is completely uncharacterized in tumorigenesis. We analyzed expression of SPATA2 and TNFA by quantitative real‐time PCR in tissues of 171 patients with low grade serous (LGSOC), high grade serous (HGSOC), endometrioid and clear cell OC compared to 28 non‐malignant control tissues. We stimulated OC cells (OVCAR3) with pro‐inflammatory (TNFα, interleukin‐1 beta (IL‐1β)) and mitogenic stimuli (IL‐6, lysophosphatidic acid) to establish a direct effect between inflammatory signaling and SPATA2. Pro‐inflammatory, but not mitogenic stimuli potently induced SPATA2 expression in OC cells. Expression of TNFA and SPATA2 was higher in OC compared to control tissues (p=0.010 and p=0.001, respectively) and correlated with each other (p=0.034, r _s=0.198). When compared with grade 1 cancers SPATA2 was expressed higher in grade 2 and 3 tumors (p=0.011) as well as in HGSOC compared to LGSOC (p=0.024). Multivariate survival analyses revealed that OCs with high SPATA2 expression were associated with reduced progression free survival (p=0.048) and overall survival (p<0.001). In conclusion, SPATA2 expression is regulated by TNFα and IL‐1β and is found to independently affect clinical outcome in OC patients. These data implicates a role of SPATA2 in tumorigenesis which warrants further investigation in gynecological malignancies.

This article is protected by copyright. All rights reserved.

http://bit.ly/2MGmK6j