Tumor necrosis factor alpha-induced protein 8 (TNFAIP8) is a suppressor of TNF-α mediated apoptosis, and its expression is induced by NF-κB activation. TNFAIP8 expression is significantly increased in various cancer cell lines. A correlation between TNFAIP8 overexpression, cancer progression, and poor prognosis has been described in many reports of human solid cancers.
To clarify the functional and clinical significance of the cancer progression-related gene, TNFAIP8, in esophageal squamous cell carcinoma (ESCC), we used immunohistochemistry to demonstrate TNFAIP8 expression in ESCC. Next, TNFAIP8 expression was depleted by using siRNA to examine the function of TNFAIP8 in the proliferation and apoptosis induction of ESCC cell lines.
We detected correlations between TNFAIP8 expression and TNM stage (P < 0.001), tumor depth (P = 0.002), lymph node metastasis (P = 0.013), distant metastasis (P = 0.001), lymphatic invasion (P < 0.001), and venous invasion (P < 0.001) among the clinicopathological characteristics of ESCC patients, and high TNFAIP8 expression was found in poor survival. TNFAIP8 depletion was significantly associated with apoptosis induction after cisplatin administration and reduced proliferation.
Our results suggest that TNFAIP8 might be an effective therapeutic target for ESCC in the future.
[Show abstract][Hide abstract] ABSTRACT: Non-Hodgkin's lymphoma (NHL) has been reported to be associated with autoimmune and pro-inflammatory response, and genetic polymorphisms of candidate genes involved in autoimmune and pro-inflammatory response may influence the susceptibility to NHL. To evaluate the role of such genetic variations in risk of NHL, we conducted a case-control study of 514 NHL patients and 557 cancer-free controls in a Chinese population.
We used the Taqman assay to genotype six potentially functional single nucleotide polymorphisms (SNPs) in six previously reported inflammation and immune-related genes (TNF rs1799964T>C, LTA rs1800683G>A, IL-10 rs1800872T>G, LEP rs2167270G>A, LEPR rs1327118C>G, TNFAIP8 rs1045241C>T). Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI).
We observed a significantly increased risk of NHL associated with the TNFAIP8 rs1045241C>T polymorphism (adjusted OR = 3.03; 95% CI = 1.68-5.45 for TT vs. CC and adjusted OR = 2.03; 95% CI = 1.53-2.69 for CT/TT vs. CC). The risk associated with the T allele was more evident in subgroups of 40-60 year-old, non-smokers or light-smokers (less than 25 pack-years), and subjects with normal weight or overweight. Risk for both B and T cell non-Hodgkin's lymphoma was elevated for CT/TT genotypes (adjusted OR = 1.95, 95% CI = 1.41-2.70 for B cell NHL and adjusted OR = 2.22, 95% CI = 1.49-3.30 for T cell NHL), particularly for DLBCL (adjusted OR = 2.01, 95%CI = 1.41-2.85) and FL (adjusted OR = 2.53, 95% CI = 1.17-5.45). These risks were not observed for variant genotypes of other five SNPs compared with their common homozygous genotypes.
The polymorphism of TNFAIP8 rs1045241C>T may contribute to NHL susceptibility in a Chinese population. Further large-scale and well-designed studies are needed to confirm these results.
PLoS ONE 05/2012; 7(5):e37846. DOI:10.1371/journal.pone.0037846 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: TNFAIP8 is an anti-apoptotic and pro-oncogenic signaling molecule involved in the process of immunity, carcinogenesis and tumor progression. Single nucleotide polymorphisms (SNPs) at microRNA binding sites may change mRNA target gene function, thus leading to cancer susceptibility and tumor progression. In this study of 1,584 cervical cancer cases and 1,394 cancer-free female controls, we investigated associations between three potentially functional SNPs in TNFAIP8 family genes and cervical cancer risk as well as platinum resistance and clinical outcomes in Eastern Chinese women. We found that the TNFAIP8-rs11064 variant GG genotype was associated with an increased risk of cervical cancer compared with AA/AG genotypes (adjusted OR=2.16, 95% CI=1.16-4.03, P=0.015). Further in vitro and ex vivo functional experiments demonstrated that the TNFAIP8-rs11064 variant G allele weakened the binding affinity of miR-22 to TNFAIP8 3'-UTR in four cancer cell lines, resulting in increased production of the TNFAIP8 protein in the patients' cervical tissues. In the survival subset, the high TNFAIP8 protein expression was significantly associated with both resistances to cisplatin and nedaplatin and recurrence and death from cervical cancer. Taken together, although lacked information on human papillomavirus (HPV) infection, the TNFAIP8-rs11064 SNP may function by affecting the affinity of miR-22 binding to the 3'-UTR of TNFAIP8 and regulating TNFAIP8 expression, thus contributing to cervical cancer risk. Additionally, the increased TNFAIP8 protein expression may predict platinum resistance and clinical outcomes in cervical cancer patients. Larger, prospective studies with detailed HPV infection data are warranted to validate our findings.
[Show abstract][Hide abstract] ABSTRACT: Background:
Tumour necrosis factor-α-induced protein 8 (TNFAIP8) has been recently documented in various malignancies, but its role in epithelial ovarian cancer (EOC) remains unknown.
Tumour necrosis factor-α-induced protein 8 expression was determined by real-time reverse transcription PCR and western blot analysis. Tumour tissues, consisting of serous, mucinous, endometrioid and clear cell histotypes, from 202 EOC patients (International Federation of Gynecologists and Obstetricians I–IV) who underwent primary cytoreduction were collected. Then, we examined the immunohistochemical expression of TNFAIP8 and evaluated its clinical significances.
Tumour necrosis factor-α-induced protein 8 overexpression was significantly associated with high histologic grade (P=0.005), large residual tumour size (P=0.014), recurrence (P=0.024) and response to chemotherapy (P<0.001). Multivariate analysis showed that TNFAIP8 overexpression was independently correlated with the presence of lymph node (odds ratio (OR): 4.129; 95% confidence interval (CI): 1.491–11.435; P=0.006) and intraperitoneal metastasis (OR: 2.209; 95% CI: 1.174–4.156; P=0.014). Moreover, results revealed that the status of TNFAIP8 expression was an independently prognostic factor for both cancer-specific survival (hazard ratio (HR): 1.852; 95% CI: 1.322–2.594; P<0.001) and disease-free survival (HR: 1.724; 95% CI: 1.235–2.407; P=0.001) in patients with EOC.
The present data provide evidence that TNFAIP8 predicts EOC metastasis and poor survival, highlighting its potential function as a therapeutic target for EOCs.
British Journal of Cancer 08/2013; 109(6). DOI:10.1038/bjc.2013.501 · 4.84 Impact Factor
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