Variation in NF-κB Signaling Pathways and Survival in Invasive Epithelial Ovarian Cancer

Abstract

Survival in epithelial ovarian cancer (EOC) is influenced by the host immune response, yet the key genetic determinants of inflammation and immunity that impact prognosis are not known. The nuclear factor-kappa B (NF-κB) transcription factor family plays an important role in many immune and inflammatory responses, including the response to cancer. We studied common inherited variation in 210 genes in the NF-κB family in 10,084 patients with invasive EOC (5,248 high grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous) from the Ovarian Cancer Association Consortium. Associations between genotype and overall survival were assessed using Cox regression for all patients and by major histology, adjusting for known prognostic factors and correcting for multiple testing (threshold for statistical significance—p < 2.5×10−5). Results were statistically significant when assessed for patients of a single histology. Key associations were with CARD11 (caspase recruitment domain family, member 11) rs41324349 in patients with mucinous EOC (HR 1.82, 95% CI 1.41-2.35, p=4.13×10−6) and TNFRSF13B (tumor necrosis factor receptor superfamily, member 13B) rs7501462 in patients with endometrioid EOC (HR 0.68, 95% CI 0.56-0.82, p=2.33×10−5). Other associations of note included TRAF2 (TNF receptor-associated factor 2) rs17250239 in patients with high-grade serous EOC (HR 0.84, 95% CI 0.77-0.92, p=6.49×10−5) and PLCG1 (phospholipase C, gamma 1) rs11696662 in patients with clear cell EOC (HR 0.43, 95% CI 0.26-0.73, p=4.56×10−4). These associations highlight the potential importance of genes associated with host inflammation and immunity in modulating clinical outcomes in distinct EOC histologies.

Long Non-Coding RNA LINC01260 Inhibits the Proliferation, Migration and Invasion of Spinal Cord Glioma Cells by Targeting CARD11 Via the NF-κB Signaling Pathway

“…CARD11 might interact with the pro-apoptotic protein Bcl-10, and CARD11 overexpression may enhance NF-κB activation [46]. In addition, oncogenic mutations in CARD11 are reportedly related to several types of lymphoma progression [31], and CARD11 expression in leukocytes suggests that it might influence immune/inflammatory responses to epithelial ovarian cancer [44]. Thus, we conclude that suppression of CARD11 suppresses proliferation and invasion and facilitates apoptosis of glioma cells via the NF-κB pathway.…”

“…Furthermore, NF-κB is involved in prostatic disease progression (neoplasic and inflammatory) [42], and it has been shown that the oncogenic risk of constitutive NF-κB activation due to germline CARD11 gain-of-function (GOF) mutations might elevate B-cell malignancy resulting from a larger number of naïve B cells [43]. The NF-κB transcription factor family has great effects on many inflammatory and immune responses, including the response to cancer [44]. Although the specific mechanism of lncRNAs is well understood, most lncRNAs exert their biological function via interaction with other molecules [45], such as microRNAs, other lncRNAs, genomic DNA, and, in particular, proteins involved in vital pathways such as NF-κB signaling [45].…”

High throughput proteomics identifies 484 high-accuracy plasma protein biomarker signatures for ovarian cancer

“…TRAF2 (TNF receptor-associated factor 2) regulates activation of NF-kappa-B and JNK and is involved in apoptosis. Genetic polymorphisms in this gene have been associated with high-grade serous ovarian cancer and patients with clear cell ovarian carcinoma 18 . NID2 (Nidogen-2) has been proposed as blood biomarker for ovarian cancer and is strongly correlated to CA125 levels 19 .…”

Ampelopsin reduces the migration and invasion of ovarian cancer cells via inhibition of epithelial-to-mesenchymal transition

“…NF-κB, a pleiotropic transcription factor, plays important roles in pathological processes associated with cancer development, such as proliferation, migration, invasion, angiogenesis, drug resistance and inflammation (21)(22)(23). It was also found in previous studies that the induction of EMT was closely associated with the activation of NF-κB.…”