Figure 4 The relationship between the expression level of genes which participate in IFN production (TLR7, MyD88, IRAK1, and IRF7) in the liver of CH patients and IL28B genotype. Table 7 Quality of NR-prediction by DLDA with IFN related gene and IL28B polymorphism A.IFN+IL28B. Table 8 Quality of NR-prediction selleck chem by DLDA with IFN related gene only. Discussion Our comprehensive analysis identified 66 genes with expression levels that consistently differed depending on the drug response of 87 CH patients and 5 normal liver specimens (Figure 1). Comparing the gene expression pattern in NR and NL showed the expression levels of 31 genes were significantly different (Table 3). In addition, most genes with expression levels in NR that were higher or lower than in NL, also differed between NR and SVR.

Therefore, it is possible that innate immunity in the early period of HCV infection strongly influences IFN reaction. HCV infection induces the impairment of cell subset number and the function of plasmacytoid dendritic cells (PDC) and natural killer cells [15]. The amount of PDC, which are the most potent producers of antiviral Type-I and III IFN [16], decreased in patients’ peripheral blood [17], however, PDC was trapped in the HCV infected liver tissue. Therapeutic non-responders had increased PDC migration to inflammatory chemokines before therapy, compared with therapeutic responders [18]. This situation resulted in elevated expressions of IFN-related genes in the CH samples and was associated with their inability to eliminate the virus [19].

Inadequate expression of IFN related genes has been associated with several diseases. High expression of ISG can induce a refractory state in IFN therapy [20] and impaired IFN production leads to high risk of HCV-related hepatocarcinogenesis [21]. Lymphocyte IFN signaling was less responsive in patients with breast cancer, melanoma, and gastrointestinal cancer and these defects may represent a common cancer-associated mechanism of immune dysfunction. Alternately, since immunotherapeutic strategies require functional immune activation, such impaired IFN signaling may hinder therapeutic approaches designed to stimulate anti-tumor immunity [22]. In this way, the dysregulation of the IFN system can influence the progression of diseases and decrease curative effects.

Genes which participate in IFN production (TLR7, MyD88, IRAK1, and IRF7) did not show any significant difference in their expression Cilengitide level prior to CH combination therapy, and their level at the clinical outcome (Figure 4A and 4B). However, the gene expression pattern of down-stream IFN pathway genes (IFI27, IFI44, ISG15, MX1, and OAS1) was significantly different among SVR, R, and NR (Table 2). IFN is usually up-regulated in HCV infected cells; however in some cases, the mechanism that controls IFN becomes abnormal, and the expression levels of IFN and ISG remain high without any curative effect [23].