Tumor necrosis factor receptor modulator spermatogenesis‐associated protein 2 is a novel predictor of outcome in ovarian cancer

Abstract

Inflammation plays a crucial role in the pathogenesis of cancer with tumor necrosis factor‐α (TNF‐α) 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 TNF‐α in ovarian cancer (OC) are inconsistent, and SPATA2 is completely uncharacterized in tumorigenesis. We analyzed expression of SPATA2 and TNFA by quantitative real‐time polymerase chain reaction in tissues of 171 patients with low‐grade serous (LGSOC), high‐grade serous (HGSOC), endometrioid and clear cell OC compared with 28 non‐malignant control tissues. We stimulated OC cells (OVCAR3) with pro‐inflammatory (TNF‐α, interleukin [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 with control tissues (P = 0.010 and P = 0.001, respectively) and correlated with each other (P = 0.034, rs = 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 with LGSOC (P = 0.024). Multivariate survival analyses revealed that OC 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 TNF‐α and IL‐1β and is found to independently affect clinical outcome in OC patients. These data implicate a role of SPATA2 in tumorigenesis which warrants further investigation in gynecological malignancies.

Deiminated proteins in extracellular vesicles and serum of llama (Lama glama)—Novel insights into camelid immunity

“…SPATA2 has been identified as a bridging factor that regulates TNF-alphA-Induced necroptosis and is instrumental for TNF-induced cell death (Elliott et al, 2016;Kupka et al, 2016;Schlicher et al, 2016;Wagner et al, 2016;Schlicher et al, 2017). SPATA2 ensures normal secretory function of Sertoli cells (Zhao et al, 2017) and has recently been identified as a novel predictor in ovarian cancer outcome (Wieser et al, 2019). While SPATA2 has been linked to ubiquination (Schlicher et al, 2016), post-translational deimination has not been invesigated.…”

SPATA2 suppresses epithelial‐mesenchymal transition to inhibit metastasis and radiotherapy sensitivity in non–small cell lung cancer via impairing DVL1/β‐catenin signaling

“…29,30 Our results in company with previous findings highly suggested that SPATA2 is tumor suppressing. However, SPATA2 was recently reported to be upregulated and its upregulation was associated with poor prognosis in ovarian cancer 31 and endometrial cancer. 32 The differences might be possibly because of the different types of cancer investigated of these studies and this also indicated that the role of SPATA2 in cancer might be context-dependent.…”

A Novel Necroptosis-Associated IncRNAs Signature for Prognosis of Head and Neck Squamous Cell Carcinoma

“…TNF-α pathway modulates immune responses ( Swann et al, 2008 ). TNF-α and IL-1β induced SPATA2 expression in ovarian cancer cells and that increased SPATA2 expression was associated with poor prognosis of ovarian cancer patients ( Wieser et al, 2019 ). Our study suggested SPATA2 expression is also associated with poor prognosis of HNSCC patients.…”