Prognostic Significance of Nuclear Factor Kappa B Expression in Locally Advanced Cervical Cancer Patients Treated Definitively With Concurrent Chemoradiation

Abstract

Objectives: Nuclear factor kappa B (NFkB) is a transcription factor shown to confer treatment resistance in tumors. A previous report suggested an association between pretreatment NFkB and poorer outcomes for cervical cancer patients treated with chemoradiation therapy (CRT). We aimed to validate their findings in a larger patient cohort. Materials and Methods: This Institutional Review Board approved study included patients with locally advanced cervical cancer patients treated with CRT. Evaluation of both nuclear and cytoplasmic immunoreactivity for NFkB was scored semiquantitatively by 3 pathologists. Cytoplasmic positivity incorporated both the intensity and percentage of immunoreactivity in invasive carcinoma (H-score), whereas nuclear positivity was assessed by percentage of positive cells. Outcomes were stratified by NFkB overexpression and tumor characteristics. Overall survival (OS), progression-free survival (PFS), distant metastases-free survival (DMFS), and local regional control (LC) were obtained using Kaplan-Meier and differences between groups were evaluated by the log-rank test. Hazard ratios were obtained using Cox regression for both univariate and multivariate analyses. Results: The mean age was 51 years old and most (78.57%) had locally advanced disease. Five-year OS, PFS, LC, and DMFS in the entire cohort were 57.18% (confidence interval [CI], 34.06%-74.82%), 48.07% (CI, 25.50%-67.52%), 72.11% (CI, 49.96%-85.73%), and 62.85% (CI, 36.33%-80.82%), respectively. There was no significant association between NFkB expression (H-index ≥180) and 3-year and 5-year OS (P-value=0.34), PFS (P-value=0.21), LC (P-value=0.86), or DMFS (P-value=0.18). Conclusions: Our study demonstrated that cytoplasmic NFkB-p65 expression (H-index ≥180) was associated with a nonstatistically significant trend toward poor clinical outcomes in locally advanced cervical cancer patients treated definitively with CRT.

Prediction of the Mechanisms by Which Quercetin Enhances Cisplatin Action in Cervical Cancer: A Network Pharmacology Study and Experimental Validation

“…Studies have demonstrated that NF-κB is a key factor to confer drug resistance in human cancer ( 61 ). The cytoplasmic NF-κB expression is correlated with a trend toward poor outcomes in locally advanced cervical cancer patients after chemoradiation therapy ( 62 ). Our results demonstrated that quercetin combined with cisplatin has a synergistic effect on cervical cancer, leading to decreased protein expression of EGFR, MYC, CCND1, and ERBB2.…”

Prevotella as the hub of the cervicovaginal microbiota affects the occurrence of persistent human papillomavirus infection and cervical lesions in women of childbearing age via host NF‐κB/C‐myc

“…16 Subsequent studies have revealed that TLR2/4/ 9 expression shows positive correlations with progression. [17][18][19] Altoos et al 20 demonstrated that the expression level of NF-κBp65 is associated with poor clinical outcomes in patients with locally advanced cervical cancer. Another study revealed that the expression of C-myc and POU5F1B is higher in CIN grade 2 or worse (CIN2+) than in normal patients or CIN1.…”

Sulfasalazine synergistically enhances the inhibitory effects of imatinib against hepatocellular carcinoma (HCC) cells by targeting NFκB, BCR/ABL, and PI3K/AKT signaling pathway‐related proteins

“…Moreover, the c‐MET gene was found to be a potent proto‐oncogene for hepatocyte growth and regeneration. A previous study demonstrated that c‐MET gene expression affects and contributes to the expression of important downstream genes and their pathways, such as NFκB, BCR/ABL and p‐STAT‐3 [28].…”