Disease Markers - Volume 28, issue 3

Authors: Riggins, James N. | Corey, William | Fonteh, Alfred N. | Harrington, Michael G.

Article Type: Research Article

Abstract: Chronic hepatitis increases the risk of hepatocellular carcinoma (HCC). To test whether circulating proteins reflect hepatic carcinogenesis, sera from patients and controls were albumin depleted, enriched for glycoproteins, digested with trypsin, and subjected to reverse phase chromatography and tandem mass spectrometry. Alpha-fetoprotein enhancer binding protein (AFPebp), a tumor suppressor, was repeatedly identified in sera from chronic HBV hepatitis patients. We independently identified and quantified AFPebp with a deuterated, phenylisocyanate-labeled synthetic peptide standard. …Elevated AFPebp levels in sera from chronic HBV hepatitis patients decreased as cancer developed. These data suggest that rising AFPebp levels in chronic HBV hepatitis may be protective, while falling levels may contribute to HCC development. Show more

Keywords: Alpha-fetoprotein, alpha-fetoprotein enhancer binding protein, tumor suppressor, hepatitis B virus, hepatitis C virus, hepatocellular carcinoma, liquid chromatography, tandem mass spectrometry, phenylisocyanate, deuterium

DOI: 10.3233/DMA-2010-0692

Citation: Disease Markers, vol. 28, no. 3, pp. 125-135, 2010

Authors: Liu, Yi-Min | Li, Xu-Dong | Guo, Xiao | Liu, Bin | Lin, Ai-Hua | Ding, Yuan-Lin | Rao, Shao-Qi

Article Type: Research Article

Abstract: Objective: To investigate whether single nucleotide polymorphisms (SNPs) in the Mn-superoxide dismutase gene (SOD2) underlie the susceptibility to noise-induced hearing loss (NIHL). Methods: Audiometric data from 2400 Chinese Han workers who exposed to occupational noise were analyzed. DNA samples were collected from the 10% most susceptible and the 10% most resistant individuals, and five SNPs (SOD2 rs2842980, rs5746136, rs2758331, rs4880 and rs5746092) were genotyped by Taqman SNP Genotyping Kits. The SNP …main effects and interactions between noise exposure and SNP were analyzed using logistic regression. Haplotypes were analyzed by using Haploview software. Results: The CT genotype of rs4880 (SOD2 V16A SNP) was associated with a higher risk of NIHL (covariates-adjusted OR, 2.18; 95% CI, 1.34–3.54, P=0.002). Haplotype analysis revealed that the frequency of AGCCG at the five SNP loci was significantly higher in the susceptible group (P=0.020). With AGCTG as the reference, the OR (95% CI) was 2.63 (1.14, 6.06). The rs4880 polymorphisms imposed larger effects when the carriers were exposed to higher levels of noise, indicating the interaction between SNP and noise exposure. Conclusions: Our results suggest that SOD2 V16A SNP in the mitochondrial targeting sequence is associated with noise induced hearing loss in Chinese workers, and this effect was enhanced by higher levels of noise exposure. Show more

Keywords: Noise induced hearing loss, association study, SNP, Mn superoxide dismutase

DOI: 10.3233/DMA-2010-0693

Citation: Disease Markers, vol. 28, no. 3, pp. 137-147, 2010

Authors: Liang, Seng | Singh, Manjit | Gam, Lay-Harn

Article Type: Research Article

Abstract: Female breast cancer is one of the leading causes of female mortality worldwide. In Malaysia, breast cancer is the most commonly diagnosed cancer in women. Of the women in Malaysia, the Chinese have the highest number of breast cancer cases, followed by the Indian and the Malay. The most common type of breast cancer is infiltrating ductal carcinoma (IDC). A proteomic approach was applied in this study to identify changes in the protein profile of cancerous …tissues compared with normal tissues from 18 patients; 8 Chinese, 6 Malay and 4 Indian were analysed. Twenty-four differentially expressed hydrophilic proteins were identified. We evaluated the potential of these proteins as biomarkers for infiltrating ductal carcinoma based on their ethnic-specific expressions. Three of the upregulated proteins, calreticulin, 14-3-3 protein zeta and 14-3-3 protein eta, were found to be expressed at a significantly higher level in the cancerous breast tissues when compared with the normal tissues in cases of infiltrating ductal carcinoma. The upregulation in expression was particularly dominant in the Malay cohort. Show more

Keywords: Breast cancer, proteomics, biomarkers, ethnicity

DOI: 10.3233/DMA-2010-0694

Citation: Disease Markers, vol. 28, no. 3, pp. 149-165, 2010

Authors: Nicotra, Giuseppina | Manfroi, Federica | Follo, Carlo | Castino, Roberta | Fusco, Nicola | Peracchio, Claudia | Kerim, Simonetta | Valente, Guido | Isidoro, Ciro

Article Type: Research Article

Abstract: The lysosomal protease Cathepsin D (CD) has been implicated in the homeostasis of lymphatic tissues. We investigated whether the level of CD expression influences the progression and the clinical outcome in Non-Hodgkin's Lymphomas (NHLs). The expression of CD was assessed by immunohistochemistry and immunofluorescence in biopsies of Diffuse Large B Cell Lymphomas (DLBCL, 35 cases), Follicular Lymphomas (FL, 9 cases of grade I-II plus 14 cases of grade IIIB), Chronic Lymphocytic Leukaemias (CLL, 17 cases) and …Peripheral T-cell Lymphomas (PTCL, 5 cases). CD staining showed a cytoplasmic punctate pattern compatible with its lysosomal localization. Based on the level of CD expression and the proportion of positive cells, lymphomas were classified as 'low expressing' (< 20% of tumor cells) or 'highly expressing' (⩾ 20% of tumor cells). Lymphomas highly expressing CD were associated with a worse stage (III-IV) at diagnosis (31/34 cases; p=0.002) and with a poor clinical outcome (i.e., partial remission and death; 28/34 cases; p=0.03). In the subgroup of aggressive/high grade of malignancy lymphomas (i.e., DLBCL, FL IIIB and PTCL), the Kaplan-Meier curve revealed a very low cumulative overall survival probability (∼ 20% at 5 year) for patients bearing a NHL with > 40% CD-positive cells compared to that of patients bearing a NHL with < 20% CD-positive cells (∼ 70% at 5 year). This correlation was statistically significant (log-rank test, p=0.01). In Cox multivariate analysis CD failed to be a prognosticator independent of pathologic stage, though the hazard ratio confirmed the association of low expression with a better survival probability. These data indicate that the presence of a high percentage of CD-positive tumor cells negatively reflects on the progression of NHLs. Show more

Keywords: Cathepsin D, tumor marker, prognosis, lymphomas

DOI: 10.3233/DMA-2010-0698

Citation: Disease Markers, vol. 28, no. 3, pp. 167-183, 2010

Authors: Hua, Chung-Ching | Chang, Liang-Che | Tseng, Jo-Chi | Chu, Chien-Ming | Liu, Yu-Chih | Shieh, Wen-Bin

Article Type: Research Article

Abstract: Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protects against oxidative stress which is important in the pathogenesis of chronic obstructive pulmonary disease (COPD). Three single nucleotide polymorphisms and 1 triplet repeat polymorphism are found in the promoter region of the Nrf2 gene. Molecular haplotyping of the Nrf2 promoter region was performed using DNA obtained from the peripheral blood of 69 COPD patients. The luciferase activities of Nrf2 promoter constructs containing all possible …combinations of the 4 polymorphisms were determined and found to differ among the 16 haplotypes.The haplotypes isolated from the subjects were divided into 3 groups (L: low; M: medium; H: high) on the basis of luciferase activities. The proportions of subjects belonging to global initiative for chronic obstructive lung disease stage 3 or 4 decreased from the group with the LL haplotype to that with the HH haplotype. Presence of the LH or MM haplotype (hazard ratio, 3.36; 95% confidence interval, 1.16–9.69), gender (0.13; 0.02–0.67), and post-bronchodilator FEV_{1} value of predicted (0.95; 0.91–0.99) are significant predictors of respiratory failure development.The haplotype of the Nrf2 gene promoter affects its activity, and is associated with the severity and the development of respiratory failure in COPD. Show more

Keywords: Respiratory failure, COPD, haplotype, Nrf2, promoter

DOI: 10.3233/DMA-2010-0700

Citation: Disease Markers, vol. 28, no. 3, pp. 185-193, 2010