Abstract
BackgroundTumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2) is a novel target and molecule in the negative regulation of immune homeostasis. The present study aimed to investigate the dynamic expression of TIPE2 mRNA during the progression of chronic hepatitis B virus (HBV) infection.MethodsA total of 193 patients with chronic HBV infection were retrospectively recruited into this cross-sectional study, including 97 patients with chronic hepatitis B (CHB), 55 with liver cirrhosis and 41 with HBV-related hepatocellular carcinoma (HCC). TIPE2 mRNA was determined using real-time quantitative polymerase chain reaction.ResultsThe expression of TIPE2 levels in patients with HCC was significantly decreased compared with expression in patients with liver cirrhosis, CHB and healthy controls (P < 0.05); meanwhile, the TIPE2 mRNA levels in patients with CHB and liver cirrhosis were significantly increased compared with levels in healthy controls (P < 0.01). In liver cirrhosis, the TIPE2 mRNA level in the decompensated state was significantly higher than that in the compensated state (P < 0.05). In HCC patients, TIPE2 mRNA was significantly associated with venous invasion, tumor size and tumor node metastasis stage. Furthermore, the optimal cutoff of 0.78 for the level of TIPE2 mRNA has a sensitivity of 97.56% and a specificity of 88.16% for discriminating HCC from patients with CHB and liver cirrhosis.ConclusionsTIPE2 mRNA was associated with various stages of chronic HBV infection, ranging from CHB to liver cirrhosis and HCC. Furthermore, TIPE2 mRNA with an optional cutoff value of 0.78 might serve as a promising biomarker to discriminate HBV-associated HCC from CHB and LC patients.
Highlights
Tumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2) is a novel target and molecule in the negative regulation of immune homeostasis
Expression profile of TIPE2 mRNA from peripheral blood mononuclear cells (PBMCs) of HBVinfected patients The levels of TIPE2 mRNA were significantly upregulated in patients with chronic hepatitis B (CHB) and Liver cirrhosis (LC) compared with the levels in healthy controls (CHB: 2.1[1.24, 2.91] vs. 1.00[0.94, 1.33], P < 0.01; LC: 1.74[1.34, 3.05] vs. 1.00[0.94, 1.33], P < 0.01), whereas there were no significant differences between CHB patients and LC patients
TIPE2 mRNA was significantly downregulated in hepatocellular carcinoma (HCC) patients compared with the levels in LC (0.45[0.30–0.61] vs. 1.74[1.34, 3.05], P < 0.05), CHB (0.45[0.30–0.61] vs. 2.1[1.24, 2.91], P < 0.05), and healthy controls (0.45[0.30–0.61] vs. 1.00[0.94, 1.33], P < 0.05) (Fig. 2a)
Summary
Tumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2) is a novel target and molecule in the negative regulation of immune homeostasis. TIPE2, tumor necrosis factor-alpha-induced protein 8 (TNFAIP8)-like 2 (TNFAIP8L2), is a newly identified negative regulator of innate immunity and cellular immunity [7]. Similar to other TNFAIP8 proteins, TIPE2 interacts with caspase-8 through their respective DED domains and promotes factor-associated suicide (Fas)induced apoptosis [7]. It has been shown that TIPE2 binds to the rat sarcoma (Ras)-interacting domain to inhibit Ras-induced tumorigenesis [11]. These results suggest that TIPE2 may be involved in inflammation and in cancer development
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