Identification of PD-1 as a unique marker for failing immune reconstitution in HIV-1-infected patients on treatment

PD-1 expression on T cells correlates with T-cell exhaustion and disease progression in HIV-infected patients. Previous studies have shown that combinational antiretroviral therapy induced viral suppression results in immune restoration and reduced PD-1 expression. However, a significant number of patients fail to restore CD4 T cells despite suppression of HIV replication below limit of quantification. In this study, we have analyzed PD-1 expression on CD4 and CD8 T cells in patients with poor immune reconstitution despite successful highly active antiretroviral therapy. We found that T cells of such patients express significantly higher levels of PD-1 than patients who had normal recovery of CD4 cells after treatment. In contrast, failing immune reconstitution was not associated with the expression of activation markers, indicating that PD-1 is a unique marker for failing immune reconstitution despite viral suppression. Furthermore, we show that T cells from patients with poor immune recovery differ from T cells of elderly in respect of their marker profile. PD-1 expression negatively correlated with individual CD4 cell counts, and PD-1 expressing T cells were more prone to programmed death ligand-mediated inhibition of T-cell proliferation, indicating that PD-1-mediated T-cell suppression may have a role in impaired immune reconstitution in HIV patients.     

Effects of intracerebral hemorrhage and subsequent minimally invasive hematoma aspiration on expression of apoptosisrelated genes in rats

This study was to investigate the effects of intracerebral hemorrhage (ICH) and subsequent minimally invasive hematoma aspiration on the expression of apoptosis-related genes in rats. IV-collagenase was injected to the caudate nucleus of the rats to make ICH models. In the control group, 30 Sprague-Dawley (SD) rats were mock treated with saline instead of collagenase. Thirty SD rats with successful modeling were designated as the ICH group. Twenty-five SD rats with successful modeling and subsequent minimally invasive hematoma aspiration were designated as the therapy group. Expression of heat shock protein 70 (Hsp70), B-cell leukemia/lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) in the brain tissues was detected by immunohistochemical assays. The expression of Hsp70, Bcl-2 and Bax in the control group was very low, and significantly increased in the ICH group and the therapy group. At each indicated time point, Hsp70 expression in the therapy group was significantly lower than that of the ICH group, Bax expression in the therapy group was significantly lower than that of the ICH group and Bcl-2 expression in the therapy group was significantly higher than that of the ICH group. These results suggest that ICH led to increased expression of apoptosis-related genes in the brain tissues. Hematoma aspiration up-regulated ICH induced Bcl-2 expression while down-regulated ICH induced Hsp70 and Bax expression.     

Prognostic significance of drug-regulated genes in high-grade osteosarcoma.

About 25-45% of patients with high-grade osteosarcoma poorly respond to chemotherapy with an increased risk of relapse and the development of metastasis. Therefore, the aim of this study was the evaluation of the prognostic value of eight previously identified drug-regulated candidate genes on osteosarcoma therapy outcome. Gene expression of 8 candidate genes was analyzed in 35 formalin-fixed, paraffin-embedded, laser-microdissected osteosarcoma biopsies. The prognostic value of these genes was evaluated by the correlation of gene expression with therapy outcome, overall survival and event-free survival in univariate and multivariate analysis. Upon univariate analysis, the expression of MALAT-1, IMPDH2, FTL and RHOA significantly correlated with response to chemotherapy. Expression of all four genes was increased in the poor responder group. Upon multivariate analysis, IMPDH2 maintained its independent prognostic value (P=0.025). Concerning the overall survival of the patients, we observed a significant association with the expression of FTL, PHB, ATAD2, ACTN1 and RRM2 as well as lactate dehydrogenase serum levels. In the subgroups of patients with high expression of these genes and those with elevated lactate dehydrogenase levels, the mean overall survival was decreased 1.7-, 1.9-, 2.2-, 2.4-, 1.5- and 4.5-fold, respectively. Except RRM2, all genes and lactate dehydrogenase serum levels remained significant in the multivariate analysis. In addition, the event-free survival was significantly decreased in the subgroups of patients with high FTL, ATAD2 and IMPDH2 expression (1.8-, 6.3- and 2.4-fold, respectively). These data demonstrate that among the identified genes are valuable markers for the prediction of osteosarcoma therapy outcome. Especially IMPDH2 and FTL are promising candidates for the stratification of osteosarcoma patients into low- and high-risk groups. Owing to their involvement in drug action these genes may further be potential targets for the modulation of drug sensitivity.     

Differentially expressed genes in human peripheral blood as potential markers for statin response

There is a considerable inter-individual variation in response to statin therapy and one third of patients do not meet their treatment goals. We aimed to identify differentially expressed genes that might be involved in the effects of statin treatment and to suggest potential markers to guide statin therapy. Forty-six healthy Korean subjects received atorvastatin; their whole-genome expression profiles in peripheral blood were analyzed before and after atorvastatin administration in relation with changes in lipid profiles. The expression patterns of the differentially expressed genes were also compared with the data of familial hypercholesterolemia (FH) patients and controls. Pairwise comparison analyses revealed differentially expressed genes involved in diverse biological processes and molecular functions related with immune responses. Atorvastain mainly affected antigen binding, immune or inflammatory response including interleukin pathways. Similar expression patterns of the genes were observed in patients with FH and controls. The Charcol-Leyden crystal (CLC), CCR2, CX3CR1, LRRN3, FOS, LDLR, HLA-DRB1, ERMN, and TCN1 genes were significantly associated with cholesterol levels or statin response. Interestingly, the CLC gene, which was significantly altered by atorvastatin administration and differentially expressed between FH patients and controls, showed much bigger change in high-responsive group than in low-responsive group. We identified differentially expressed genes that might be involved in mechanisms underlying the known pleiotropic effects of atorvastatin, baseline cholesterol levels, and drug response. Our findings suggest CLC as a new candidate marker for statin response, and further validation is needed.     

Conversion therapy combined with individualized surgical treatment strategy improves survival in patients with colorectal cancer liver metastases

Objective: To explore surgical treatment strategies for patients with liver metastases from colorectal cancer (CRLM), and analyze the prognosis and influencing factors. Methods: The clinical data of 156 inpatients with CRLM admitted to our hospital from January 2009 to June 2019 were retrospectively analyzed. Patients were divided into initially resectable group (80 cases) and initially unresectable group (76 cases). For patients with initially unresectable CRLM, conversion therapy (chemotherapy plus targeted therapy) combined with individualized surgical treatment strategy was used. The individualized surgical treatment strategy mainly included hepatectomy combined with ablation. Portal vein ligation and staged resection were adopted according to the patients’ specific conditions. All patients were followed up until death. The Kaplan-Meier method and Log-rank test were used for survival analysis. Results: Median overall survival (OS) time of patients in the initially resectable group and initially unresectable group were 36 months and 17 months, respectively (P = 0.001). Median OS time of 24 patients who underwent surgical resection after successful conversion therapy was significantly longer than that of 52 patients with unsuccessful conversion therapy (20 months versus 15 months, respectively, P = 0.034). Univariate analysis showed that a maximum diameter of liver metastases < 6 cm and a number of metastases ≤ 4 were independent factors associated with successful conversion therapy. According to patients’ specific conditions, 6 cases accepted hepatectomy combined with ablation, and 1 case accepted portal vein ligation and staged resection. Conclusion: Treatment of patients with CRLM should follow the principles of standardization and individualization. For patients with initially unresectable CRLM, successful conversion therapy should be pursued whenever possible. The maximum size and number of liver metastases were significantly associated with successful conversion therapy. Surgical resection-based comprehensive treatment is key.     

Expression of cytokine- and chemokine-related genes in peripheral blood mononuclear cells from lupus patients by cDNA array

Systemic lupus erythematosus (SLE) is characterized by diverse and complex immune abnormalities. In an effort to begin to characterize the full complexity of immune abnormalities, the expression pattern of 375 potentially relevant genes was analyzed using peripheral blood mononuclear cells (PBMC) from 21 SLE patients and 12 controls by cDNA arrays. When mean gene expression for patients was compared to controls, 50 genes were identified that exhibited more than 2.5-fold difference in expression level. By the Mann-Whitney U test, 20 genes were significantly different (P < 0.05) between patients and controls. Most of these genes have not been previously associated with SLE and belong to a variety of families such as TNF/death receptor, IL-1 cytokine family, and IL-8 and its receptors. Hierarchical clustering of samples and differentially expressed genes revealed that with few exceptions, patients clustered separately from controls. These results highlight the potential use of the microarray data in identifying genes associated with SLE, which could become candidate molecular markers or future therapeutic targets.     

Expression of a human SOCS protein, HSOCP-1, in peripheral blood eosinophils from patients with atopic dermatitis

To identify new genes related to atopic dermatitis (AD), we screened for differentially expressed genes in peripheral blood eosinophils derived from AD patients and healthy volunteers. RNA was prepared from peripheral blood eosinophils obtained from both AD patients and healthy volunteers, and the expression of various genes was monitored using fluorescent differential display and real-time RT-PCR. One of the expressed sequence tags (ESTs) was expressed at a significantly higher level in AD patients than in healthy volunteers. A full-length cDNA was identified that encoded a human suppressor of cytokine signaling (SOCS) protein, HSOCP-1, also named hASB-8. The expression of HSOCP-1 was increased in cultured peripheral blood eosinophils after IL-4 stimulation, and overexpression of HSOCP-1 caused cell death in an eosinophil cell line, AML14.3D10. p34(SEI-1) was identified as a HSOCP-1-interacting protein by a yeast two-hybrid system. It is a protein that also interacts with the cyclin-dependent kinase inhibitor p16(INK4), suggesting that HSOCP-1 is involved in cell cycle control and apoptosis.     

Circadian gene expression predicts patient response to neoadjuvant chemoradiation therapy for rectal cancer

Preoperative neoadjuvant chemoradiation therapy may be useful in patients with operable rectal cancer, but treatment responses are variable. We examined whether expression levels of circadian clock genes could be used as biomarkers to predict treatment response. We retrospectively analyzed clinical data from 250 patients with rectal cancer, treated with neoadjuvant chemoradiation therapy in a single institute between 2011 and 2013. Gene expression analysis (RT-PCR) was performed in tissue samples from 20 patients showing pathological complete regression (pCR) and 20 showing non-pCR. The genes analyzed included six core clock genes (Clock, Per1, Per2, Cry1, Cry2 and Bmal1) and three downstream target genes (Wee1, Chk2 and c-Myc). Patient responses were analyzed through contrast-enhanced pelvic MRI and endorectal ultrasound, and verified by histological assessment. pCR was defined histologically as an absence of tumor cells. Among the 250 included patients, 70.8% showed regression of tumor size, and 18% showed pCR. Clock, Cry2 and Per2 expressions were significantly higher in the pCR group than in the non-pCR group (P<0.05), whereas Per1, Cry1 and Bmal1 expressions did not differ significantly between groups. Among the downstream genes involved in cell cycle regulation, c-Myc showed significantly higher expression in the pCR group (P<0.05), whereas Wee1 and Chk2 expression did not differ significantly between groups. Circadian genes are potential biomarkers for predicting whether a patient with rectal cancer would benefit from neoadjuvant chemoradiation therapy.     

Genomics and response to long-term oxygen therapy in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide, and long-term oxygen therapy has been shown to reduce mortality in COPD patients with severe hypoxemia. However, the Long-term Oxygen Treatment Trial (LOTT), a large randomized trial, found no benefit of oxygen therapy in COPD patients with moderate hypoxemia. We hypothesized that there may be differences in response to oxygen which depend on genotype or gene expression. In a genome-wide time-to-event analysis of the primary outcome of death or hospitalization in 331 subjects, 97 single nucleotide polymorphisms (SNPs) showed evidence of interaction with oxygen therapy at P?<?1e?5, including 7 SNPs near arylsulfatase B (ARSB; P?=?6e?6). In microarray expression profiling on 51 whole blood samples from 37 individuals, at screening and/or at 12-month follow-up, ARSB expression was associated with the primary outcome depending on oxygen treatment. The significant SNPs were conditional expression quantitative trait loci for ARSB expression. In a network analysis of genes affected by long-term oxygen, two observed clusters including 26 co-expressed genes were enriched in mitochondrial function. Using data from the observational COPDGene Study, we validated the expression of 25 of these 26 genes, plus ARSB. The effect of long-term oxygen therapy in COPD varied based on ARSB expression and genotype. ARSB has previously been shown to be associated with hypoxemia in human bronchial and colonic epithelial cells and in a mouse model. In peripheral blood, long-term oxygen treatment affected expression of mitochondrial-related genes, a biologically relevant pathway in COPD. SNPs and expression of ARSB are associated with response to long-term oxygen in COPD. The ARSB SNPs were expression quantitative trait loci depending on oxygen therapy. Genes differentially expressed by long-term oxygen were enriched in mitochondrial functions. This suggests a potential biomarker to personalize use of long-term oxygen in COPD.     

Identification ACTA2 and KDR as key proteins for prognosis of PD‐1/PD‐L1 blockade therapy in melanoma

Programmed cell death protein 1 (PD‐1) /programmed cell death ligand 1 (PD‐L1) blockade is an important therapeutic strategy for melanoma, despite its low clinical response. It is important to identify genes and pathways that may reflect the clinical outcomes of this therapy in patients. We analyzed clinical dataset {"type":"entrez-geo","attrs":{"text":"GSE96619","term_id":"96619"}}GSE96619, which contains clinical information from five melanoma patients before and after anti‐PD‐1 therapy (five pairs of data). We identified 704 DEGs using these five pairs of data, and then the number of DEGs was narrowed down to 286 in patients who responded to treatment. Next, we performed KEGG pathway enrichment and constructed a DEG‐associated protein‐protein interaction network. Smooth muscle actin 2 (ACTA2) and tyrosine kinase growth factor receptor (KDR) were identified as the hub genes, which were significantly downregulated in the tumor tissue of the two patients who responded to treatment. To confirm our analysis, we demonstrated similar expression tendency to the clinical data for the two hub genes in a B16F10 subcutaneous xenograft model. This study demonstrates that ACTA2 and KDR are valuable responsive markers for PD‐1/PD‐L1 blockade therapy.     

急性心肌梗死猝死者心肌细胞hsf1和HSP70改变的意义

目的探讨急性心肌梗死猝死者梗死区心肌细胞内热休克转录因子1（hsfl）和热休克蛋白70（HSP70）改变的临床意义。方法分别用RT-PCR和免疫组化法检测（IHC）18例急性心肌梗死猝死者（研究组）和15例心脏正常因车祸快速死亡者（对照组）心肌细胞中hsfl和HSP70基因的mRNA和蛋白表达量。结果急性心肌梗死猝死者心肌细胞hsfl和HSP70的mRNA表达量都显著高于正常对照组（P〈0.01），且hsfl和HSP70mRNA的表达量之间呈显著的正相关关系（P〈0．001）。急性心肌梗死猝死者心肌细胞hsfl和HSP70蛋白在细胞浆和细胞核表达较对照组显著增强（P〈0.001），其中hsfl蛋白主要在心肌细胞核内表达，HSP70蛋白主要在心肌细胞浆内表达。结论急性心肌梗死猝死者心肌细胞内hsfl和HSPT0可能共同参与了急性心肌梗死的病理生理过程．这一过程可能是热休克反应的另一调节途径。     

Developing adenoviral vectors encoding therapeutic genes toxic to host cells: Comparing binary and single-inducible vectors expressing truncated E2F-1

Adenoviral vectors are highly efficient at transferring genes into cells and are broadly used in cancer gene therapy. However, many therapeutic genes are toxic to vector host cells and thus inhibit vector production. The truncated form of E2F-1 (E2Ftr), which lacks the transactivation domain, can significantly induce cancer cell apoptosis, but is also toxic to HEK-293 cells and inhibits adenovirus replication. To overcome this, we have developed binary- and single-vector systems with a modified tetracycline-off inducible promoter to control E2Ftr expression. We compared several vectors and found that the structure of expression cassettes in vectors significantly affects E2Ftr expression. One construct expresses high levels of inducible E2Ftr and efficiently causes apoptotic cancer cell death by activation of caspase-3. The approach developed in this study may be applied in other viral vectors for encoding therapeutic genes that are toxic to their host cells and/or inhibit vector propagation.     

Analysis of long-term gene expression in neurons of the hippocampal subfields following traumatic brain injury in rats

After experimental traumatic brain injury (TBI), widespread neuronal loss is progressive and continues in selectively vulnerable brain regions, such as the hippocampus, for months to years after the initial insult. To clarify the molecular mechanisms underlying secondary or delayed cell death in hippocampal neurons after TBI, we compared long-term changes in gene expression in the CA1, CA3 and dentate gyrus (DG) subfields of the rat hippocampus at 24 h and 3, 6, and 12 months after TBI with changes in gene expression in sham-operated rats. We used laser capture microdissection to collect several hundred hippocampal neurons from the CA1, CA3, and DG subfields and linearly amplified the nanogram samples of neuronal RNA with T7 RNA polymerase. Subsequent quantitative analysis of gene expression using ribonuclease protection assay revealed that mRNA expression of the anti-apoptotic gene, Bcl-2, and the chaperone heat shock protein 70 was significantly downregulated at 3, 6 (Bcl-2 only), and 12 months after TBI. Interestingly, the expression of the pro-apoptotic genes caspase-3 and caspase-9 was also significantly decreased at 3, 6 (caspase-9 only), and 12 months after TBI, suggesting that long-term neuronal loss after TBI is not mediated by increased expression of pro-apoptotic genes. The expression of two aging-related genes, p21 and integrin beta3 (ITbeta3), transiently increased 24 h after TBI, returned to baseline levels at 3 months and significantly decreased below sham levels at 12 months (ITbeta3 only). Expression of the gene for the antioxidant glutathione peroxidase-1 also significantly increased 6 months after TBI. These results suggest that decreased levels of neuroprotective genes may contribute to long-term neurodegeneration in animals and human patients after TBI. Conversely, long-term increases in antioxidant gene expression after TBI may be an endogenous neuroprotective response that compensates for the decrease in expression of other neuroprotective genes.     

Expression of genes related to multiple drug resistance and apoptosis in acute leukemia: response to induction chemotherapy

Resistance to chemotherapy is a major impediment to the successful treatment of acute leukemia (AL). Expression of genes involved in drug resistance and apoptosis may be responsible for this. This study aimed to investigate the expression of drug resistance (MDR1, MRP1, LRP, BCRP, GSTP1, DHFR) and apoptotic genes (p53, BCL-2, Survivin) in adult acute leukemias and compare them with clinical and hematological findings and response to induction chemotherapy. Eighty-five patients with AL [45 with acute myeloid leukemia (AML) and 40 with acute lymphoblastic leukemia (ALL)] were used as a study group. Real-time PCR results showed that expression level of MDR1 was significantly higher in AML whereas expression of DHFR, BCRP and Survivin was significantly higher in ALL patients. In AML, significant correlation was observed between LRP and MRP1 (r(s)=0.44, p=0.016), LRP and DHFR (r(s)=0.41, p=0.02), MDR1 and BCL-2 (r(s)=0.38, p=0.03). Expression of GSTP1 and LRP correlated with high white blood count (p=0.03 and p=0.03) and BCL-2 with high peripheral blast count (p=0.009). MDR1 expression was significantly associated with the expression of immature stem cell marker CD34 (p=0.002). In ALL, significant association was found between LRP gene and female sex (p<0.0001), LRP and B-ALL patients (p=0.04) and LRP and BCR/ABL positive patients (p=0.004). High expression of MDR1 and BCL-2 in AML and MRP1 gene in ALL was associated with response to induction chemotherapy (p=0.001, p=0.02 and p=0.007 respectively). These results showed the potential clinical relevance of MDR1, MRP1 and BCL-2 in adult patients with acute leukemia in the context of induction chemotherapy.     

尿毒症免疫高敏患者外周血单个核细胞基因差异表达研究

目的:从基因水平探索外周血单个核细胞(PBMCs)在尿毒症患者免疫高敏发生中的作用机制。方法:选择群体抗体反应 (PRA) >85%的尿毒症患者30例为免疫高敏组;PRA(-)尿毒症患者为对照组,均采新鲜血液。用Ficoll技术分离单个核细胞,并采用一步法提取总RNA,同组RNA样品等量混合,荧光染料标记后,逆转录合成cDNA探针。采用高通量基因表达谱芯片(16,920点基因)进行芯片杂交,扫描后得到Cy3/Cy5图像文件,筛选出基因差异表达的结果。结果: 差异性表达基因877条,上调基因88条,下调基因789条。通过资料分析,对某些基因与免疫高敏发生机制的关系进行初步探讨。 结论:外周血单个核细胞在免疫高敏发生中的作用可能与自身抗原识别、B淋巴细胞分化增强、抗凋亡作用增强和免疫抑制药物的耐药机制有关。     

Prognostic and Predictive Markers in Medullary Thyroid Carcinoma

Unlike papillary thyroid carcinoma, medullary thyroid carcinoma is insensitive to adjuvant treatment with radioactive iodine. The clinical management of patients with advanced or metastatic disease remains challenging since no effective systemic adjuvant therapy is available. We aimed to identify markers of aggressive disease and novel drugable protein targets that would provide systemic adjuvant treatment for patients with advanced medullary thyroid carcinoma. We therefore examined morphologic features of aggressive behavior and the expression of 41 proteins involved in apoptosis, cell cycle, angiogenesis, inflammation, cell adhesion, tumor-specific markers, and WNT, SHH, and AKT pathways using tissue microarray from 23 patients with medullary thyroid carcinoma. Protein expression was determined using computerized image analysis software. Statistical analysis was carried out to correlate clinical data with the average score for each marker. Angioinvasion proved to be the most reliable predictor of disease recurrence and death. The rate of angioinvasion was 43?%. All angioinvasive medullary thyroid carcinomas had locoregional and/or distant metastasis; 60?% of angioinvasive medullary thyroid carcinomas developed distant metastasis. We identified expression of several potentially important protein targets such as COX-1/2, Bcl-2a, Gst-??, Gli-1, Gli-2, Gli-3, and Bmi-1 that may be therapeutically targeted in medullary thyroid carcinoma. More importantly, the immunohistochemical profile of SSTRs in medullary thyroid carcinoma may also have clinical relevance for the administration of peptide receptor radionuclide treatment. Successful outcome of clinical trials directed against these novel targets would provide much needed systemic adjuvant treatment for patients with advanced medullary thyroid carcinoma, and our data suggest the possibility of stratifying patients who are likely to require adjuvant therapy before their burden of disease precludes successful therapeutic effect.     

Gene expression patterns in livers of Hispanic patients infected with hepatitis C virus

We report a gene expression study aimed at the identification of genes differentially expressed in the livers of Hispanic patients infected with hepatitis C virus (HCV). Six uninfected controls were compared with 14 HCV(+) patients in which the liver biopsies were obtained at the time of diagnosis. Among the latter, five patients were also analyzed 4 weeks after the onset of standard anti-HCV therapy (pegylated interferon-α +?ribavirin). We identified many genes up- or down-regulated by the infection with HCV in the human livers. When these genes were subjected to pathway analysis, several prominent pathways were revealed including many interferon (IFN)-inducible pathways as well as immune cell trafficking, inflammation, anti-microbial responses, and even cancer. We detected expression of many genes that have previously been associated with HCV infection, as well as several novel genes including CD47. The genes induced by HCV infection showed large expression changes, whereas the genes induced by the IFN-α combination therapy were relatively few (including MX2, ORMDL3, GPAM, KOPX18, TMEM56, and HBP1) and they reflected relatively small expression changes. This is the first study to identify changes in gene expression in livers of HCV(+) Hispanic patients and the first to identify genes induced by anti-HCV combination therapy in the human liver.     

Expression of interferon receptor genes in the liver as a predictor of interferon response in patients with chronic hepatitis C.

Interferon (IFN) receptor mRNA expression patterns in the liver have been shown to correlate with the effectiveness of IFN therapy in patients with hepatitis C virus (HCV) infection. However, it is not clear to what extent this factor contributes to the short (primary)- and long (sustained)-term results of IFN treatment with respect to biochemical and virological remission. Eighty-two patients who subsequently received lymphoblastoid IFN-alpha therapy underwent liver biopsies before IFN therapy. Possible factors that might correlate with IFN response were chosen and analyzed. The primary biochemical and virological responses at the end to treatment (24 weeks) were 63% and 43% vs. 46% and 32% for sustained biochemical and virological remission at the end of follow-up (48 weeks), respectively. In univariate analysis, the absence of HCV genotype 1b, a low titer of HCV RNA, and the expression of IFN receptor mRNA were significantly correlated with sustained biochemical and virological responses to IFN therapy. Multiple logistic regression analysis showed that IFN receptor mRNA expression and the absence of genotype 1b were significant predictors of the sustained biochemical and virological effectiveness of IFN therapy. IFN receptor mRNA expression predicted a sustained virological response to IFN therapy with a positive predictive value of 100% with genotype non-1b and had a negative predictive value of 97% with genotype 1b. It is concluded that expression of IFN receptor genes in the liver is a useful index for predicting the short- and long-term efficacy of IFN therapy in patients with chronic HCV infection.