Our previous genome-wide association studies on SLE have identified several susceptibility genes involved in NF-κB signaling pathway, including TNFSF4, TNFAIP3, TNIP1, BLK, SLC15A4 and UBE2L3. The aim of this study is to investigate the association model (additive, dominant, recessive) of these genes and search for possible gene-gene interactions between them. In this study, we explored the association model of these six genes and search for possible gene-gene interactions based on identified single-nucleotide polymorphisms (SNPs) among them by using logistic regression analysis in the combined sample of 4,199 cases and 8,255 controls. The most significant association evidence was observed under recessive model for all of these SNPs. Besides, significant interactions between these SNPs were observed in this study: the TNFSF4 and TNIP1 SNPs (P adjusted = 1.68E-10), the TNFSF4 and SLC15A4 SNPs (P adjusted = 3.55E-08), the TNFSF4 and UBE2L3 SNPs (P adjusted = 8.74E-13), the TNIP1 and BLK SNPs (P adjusted = 9.45E-10), the TNIP1 and UBE2L3 SNPs (P adjusted = 8.25E-11), the TNFAIP3 and UBE2L3 SNPs (P adjusted = 3.06E-14) and the BLK and SLC15A4 SNPs (P adjusted = 4.51E-12). These results may contribute to our understanding of SLE genetic interactions and account for the additional risk of certain patients to develop SLE.

Ikaros family zinc finger 1, encoded by IKZF1, are lymphoid-restricted zinc finger transcription factors that share common N-terminal Kruppel-like zinc finger DNA-binding domain. IKZF1 play multiple important roles on regulators of lymphocyte differentiation and hematological tumor suppressor. Our genome-wide association (GWA) studies in systemic lupus erythematosus (SLE) independently identified genetic variants in IKZF1 associated with SLE, which are supported by other studies. Previous studies found that lower expression of IKZF1 may play critical roles in activating some signal pathways involved in SLE, such as signal transducers and activators of transcription (STAT)4 and interferon pathways. In addition, IKZF1 has been implicated in roles involved in some hematologic traits or abnormalities, such as erythrocyte measures, myelofibrosis, and acute lymphoblastic leukemia (ALL), which may be common clinical manifestations or co-occurrence hematological diseases of patients with SLE. All these findings suggest that IKZF1 may play a critical role in the pathogenesis of SLE. In this article, we discuss the existing understanding of the role of IKZF1 on the physiological and pathological functions associated with SLE, providing insights that may assist in the development of new therapeutic strategies based on IKZF1 for patients with SLE.

Background Anxiety and depression are more frequent in cancer patients than general population and may be correlated with cancer prognosis; however, their value in prostate cancer patients is largely unknown. We aimed to evaluate prevalence of anxiety and depression in prostate cancer survivors post the surgeries, and their correlations with patients’ disease-free survival (DFS) and overall survival (OS). Methods A hundred and ninety-four patients with prostate cancer who underwent radical prostatectomy were enrolled. After discharged from hospital, patients were assessed for post-surgery anxiety and depression every 3 months using Zung Self-rating Anxiety/Depression Scale (SAS/SDS) for a total of 36 months. In addition, disease conditions, DFS, and OS were also documented. Results SAS score (P < 0.001), anxiety rate (P = 0.004), SDS score (P < 0.001), and depression rate (P < 0.001) gradually elevated from baseline to month 36 in prostate cancer patients. Anxiety at baseline (P = 0.009) and anxiety at 3 years (P = 0.017) were correlated with worse DFS, and anxiety at baseline (P = 0.009) was also correlated with shorter OS in prostate cancer patients. Furthermore, depression at baseline (P = 0.005) and depression at 2 years (P = 0.008) were associated with unfavorable DFS, and depression at baseline (P = 0.001), 1 year (P = 0.025), and 2 years (P = 0.008) were associated with worse OS in prostate cancer patients. Moreover, multivariate Cox’s proportional hazards regression analysis elucidated that depression at baseline (P = 0.027) was an independent predictive factor for shorter DFS in prostate cancer patients. Conclusion Anxiety and depression both gradually deteriorate, and they correlate with unfavorable survival profile in prostate cancer patients after radical prostatectomy.