Disease Markers - Volume 30, issue 4

Authors: Vasiljević, Nataöa | Wu, Keqiang | Brentnall, Adam R. | Kim, Dae Cheol | Thorat, Mangesh A. | Kudahetti, Sakunthala C. | Mao, Xueying | Xue, Liyan | Yu, Yongwei | Shaw, Greg L. | Beltran, Luis | Lu, Yong-Jie | Berney, Daniel M. | Cuzick, Jack | . Lorincz, Attila T

Article Type: Research Article

Abstract: Aberrant DNA methylation plays a pivotal role in carcinogenesis and its mapping is likely to provide biomarkers for improved diagnostic and risk assessment in prostate cancer (PCa). We quantified and compared absolute methylation levels among 28 candidate genes in 48 PCa and 29 benign prostate hyperplasia (BPH) samples using the pyrosequencing (PSQ) method to identify genes with diagnostic and prognostic potential. RARB, HIN1, BCL2, GSTP1, CCND2, EGFR5, APC, RASSF1A, MDR1, NKX2-5, CDH13, DPYS, PTGS2, …EDNRB, MAL, PDLIM4, HLAa, ESR1 and TIG1 were highly methylated in PCa compared to BPH (p < 0.001), while SERPINB5, CDH1, TWIST1, DAPK1, THRB, MCAM, SLIT2, CDKN2a and SFN were not. RARB methylation above 21% completely distinguished PCa Separation based on methylation level of SFN, SLIT2 and SERPINB5 distinguished low and high Gleason score cancers, e.g. SFN and SERPINB5 together correctly classified 81% and 77% of high and low Gleason score cancers respectively. Several genes including CDH1 previously reported as methylation markers in PCa were not confirmed in our study. Increasing age was positively associated with gene methylation (p < 0.0001). Accurate quantitative measurement of gene methylation in PCa appears promising and further validation of genes like RARB, HIN1, BCL2, APC and GSTP1 is warranted for diagnostic potential and SFN, SLIT2 and SERPINB5 for prognostic potential. Show more

Keywords: Prostate cancer, BPH, DNA Methylation, pyrosequencing, biomarker

DOI: 10.3233/DMA-2011-0790

Citation: Disease Markers, vol. 30, no. 4, pp. 151-161, 2011

Authors: Kumar, Vivek | Yadav, Chandra Shekhar | Datta, Sudip Kumar | Singh, Satyender | Ahmed, Rafat S | Goel, Sanjay | Gupta, Sanjay | Mustafa, Md. | Grover, Rajesh Kumar | Basu Dev Banerjee,

Article Type: Research Article

Abstract: Association of glutathione S-transferase (GST) M1 and T1 deletions with benign prostate hyperplasia (BPH) and prostate cancer is well reported. These enzymes metabolize numerous toxins thus protecting from oxidative injury. Oxidative stress has been associated with development of BPH and prostate cancer. The present study was designed to analyze role of GST deletions in development of oxidative stress in these subjects. GSTs are responsible for metabolism of toxins present in tobacco therefore …effect of tobacco usage in study groups was also studied. Three groups of subjects: BPH (57 patients), prostate cancer (53 patients) and controls (46 subjects) were recruited. Genotyping was done using a multiplex polymerase chain reaction (PCR) method. Malondialdehyde (MDA) levels as marker of oxidative stress were estimated by measuring thiobarbituric acid reactive substance (TBARS) in plasma. Based on genotyping, subjects were categorized into: GSTM1+/GSTT1+, GSTM1-/GSTT1+, GSTM1+/GSTT1- and GSTM1-/GSTT1-. Significantly higher plasma MDA levels were noticed in GSTM1-/GSTT1- as compared to GSTM1+/GSTT1+ in all study groups. Double deletion (GSTM1-/GSTT1-) is associated with higher oxidative stress which might play a role in the pathogenesis of BPH and prostate cancer. However, other markers of oxidative stress should be analyzed before any firm conclusion. Show more

Keywords: Glutathione S-transferase, malondialdehyde, genotypes, deletion

DOI: 10.3233/DMA-2011-0774

Citation: Disease Markers, vol. 30, no. 4, pp. 163-169, 2011

Authors: Wang, Gang | Kwan, Bonnie Ching-Ha | Lai, Fernand Mac-Moune | Chow, Kai-Ming | Li, Philip Kam-Tao | Szeto, Cheuk-Chun

Article Type: Research Article

Abstract: Background: Previous studies suggested miR-146a and miR-155 play important roles in innate and adaptive immune responses. We studied intra-renal and urinary levels of miR-146a and miR-155 in patients with immunoglobulin A nephropathy (IgAN). Methods: Intra-renal and urinary levels of miR-146a and miR-155 are quantified in 43 patients with IgAN; the result was compared to 20 nephrectomy specimens and urine sediment of 13 healthy volunteers. Results: The levels of intra-renal and urinary levels of miR-146a and miR-155 …of IgAN are significantly higher than controls. Estimated glomerular filtration rate inversely correlates with intra-renal level of miR-146a and miR-155; proteinuria positively correlates with intra-renal level of miR-146a and miR-155, as well as urinary level of miR-146a and miR-155. Intra-renal level of miR-155 significantly correlates with tubulointerstitial scarring. Urinary level of miR-146a inversely correlates with urinary expression of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α and positively correlates with urinary expression of regulated upon activation, normal T-cell expressed, and secreted (RANTES). Urinary level of miR-155 inversely correlates with urinary expression of IL-1β and TNF-α and positively correlates with urinary expression of forkhead box P3 (FOXP3) and RANTES. Conclusion: We conclude that intra-renal and urinary levels of miR-146a and miR-155 were significantly elevated in IgAN, and the degree of upregulation correlates with clinical and histological severity of the disease. Our results suggested miR-146a and miR-155 might play an important role in the pathophysiology of IgAN. Show more

Keywords: microRNA, proteinuria, chronic renal failure

DOI: 10.3233/DMA-2011-0766

Citation: Disease Markers, vol. 30, no. 4, pp. 171-179, 2011

Authors: Du, Wei-Dong | Chen, Gang | Cao, Hui-Min | Jin, Qing-Hui | Liao, Rong-Feng | He, Xiang-Cheng | Chen, Da-Ben | Huang, Shu-Ren | Zhao, Hui | Lv, Yong-Mei | Tang, Hua-Yang | Tang, Xian-Fa | Wang, Yong-Qing | Sun, Song | Zhao, Jian-Long | Zhang, Xue-Jun

Article Type: Research Article

Abstract: Leber's hereditary optic neuropathy (LHON) is a maternally transmitted disease. Clinically, no efficient assay protocols have been available. In this study, we aimed to develop an oligonucleotide biochip specialized for detection of known base substitution mutations in mitochondrial DNA causing LHON and to investigate frequencies of LHON relevant variants in Anhui region of China. Thirty-two pairs of oligonucleotide probes matched with the mutations potentially linked to LHON were covalently immobilized. Cy5-lablled targets …were amplified from blood DNA samples by a multiplex PCR method. Two kinds of primary mutations 11778 G > A and 14484 T > C from six confirmed LHON patients were interrogated to validate this biochip format. Further, fourteen Chinese LHON pedigrees and twenty-five unrelated healthy individuals were investigated by the LHON biochip, direct sequencing and pyrosequencing, respectively. The biochip was found to be able efficiently to discriminate homoplasmic and heteroplasmic mtDNA mutations in LHON. Biochip analysis revealed that twelve of eighteen LHON symptomatic cases from the 14 Chinese pedigree harbored the mutations either 11778G > A, 14484T > C or 3460G > A, respectively, accounting for 66.7%. The mutation 11778G > A in these patients was homoplasmic and prevalent (55.5%, 10 of 18 cases). The mutations 3460G > A and 3394T > C were found to co-exist in one LHON case. The mutation 13708G > A appeared in one LHON pedigree. Smaller amount of sampling and reaction volume, easier target preparation, fast and high-throughput were the main advantages of the biochip over direct DNA sequencing and pyrosequencing. Our findings suggested that primary mutations of 11778G > A, 14484T > C or 3460G > A are main variants of mtDNA gene leading to LHON in China. The biochip would easily be implemented in clinical diagnosis. Show more

Keywords: Oligonucleotide biochip, mitochondrial DNA, point mutation, Leber's hereditary optical neuropathy

DOI: 10.3233/DMA-2011-0767

Citation: Disease Markers, vol. 30, no. 4, pp. 181-190, 2011

Authors: Bodova, Kristina Biskupska | Biringer, Kamil | Dokus, Karol | Ivankova, Jela | Stasko, Jan | Danko, Jan

Article Type: Research Article

Abstract: Objective: The purpose of this study was to examine plasma levels of fibronectin and plasminogen inhibitor type 1 (PAI-1), and alterations in uterine artery (UtA) waveforms throughout normotensive and preeclamptic pregnancies and to analyze its predictive value for the detection of preeclampsia within the second trimester of pregnancy. Material and methods: Blood samples were collected from 102 healthy, nulliparous women between the 24th and 26th gestational week. Preeclampsia developed in 13 patients; 89 normotensive …control subjects were matched from the same cohort. Plasma samples were assayed for fibronectin and PAI-1 by enzyme-linked immunosorbent assay. Color pulsed Doppler examinations of UtA were performed after blood sampling. Trends were compared between two groups. Results: Maternal plasma fibronectin and PAI-1 levels and average PI, RI and S/D ratios of patients with preeclampsia were significantly higher (p< 0.05). The best cut-off values for predicting preeclampsia of fibronectin, PAI-1, PI, RI, S/D ratio based on ROC curve analysis were 290 mg/ml, 77.3 ng/ml, 1,0615, 0.605 and 2,59 respectively. The areas under the curve equal to 0.705, 0.753, 0.689, 0.695 and 0.699 for fibronectin, PAI-1 and uterine artery Doppler PI, RI, S/D ratio were determined for the prediction of preeclampsia. Conclusions: Fibronectin, PAI-1 and UtA Doppler are potentially useful predictors of preeclampsia. Maternal plasma PAI-1 combinated with fibronectin had the highest predictive values in our study. Show more

Keywords: Preeclampsia, gestational hypertension, fibronectin, PAI-1, uterine artery Doppler

DOI: 10.3233/DMA-2011-0772

Citation: Disease Markers, vol. 30, no. 4, pp. 191-196, 2011

Authors: Al Khaldi, Rasha Mazen | Al Mulla, Fahd | Al Awadhi, Shafika | Kapila, Kusum | Mojiminiyi, Olusegun A

Article Type: Research Article

Abstract: Objectives: The aims of this study are to (1) study the influence of polymorphisms in adiponectin gene on adiponectin levels and potential associations with breast, prostate and colon cancer; (2) investigate the associations of adiponectin levels with other adipokines and breast, prostate and colon cancers. Subjects: We measured fasting adiponectin, leptin, insulin, Sex steroids in 132 (66 females, 66 males) cancer patients and 68 age and sex matched apparently healthy subjects. Body Mass Index …(BMI) and waist circumference were used as indices of obesity. Insulin Resistance was assessed using Homeostasis Model Assessment (HOMA). Three single nucleotide polymorphisms (SNP rs182052 (G-10066-A), SNP rs1501299 (276G > T), SNP rs224176 (45T > G) in adiponectin gene were studied using Real Time Polymerase Chain Reaction. Results: GG genotype of SNP rs1501299 was significantly associated with higher levels of adiponectin (OR=1.2, 95%CI(1.03–1.3), p = 0.02); breast (OR=8.6, 95%CI(1.03–71), p = 0.04), colon cancers (OR= 12, 95%CI(1.2–115), p =0.03). GT genotype was also associated significantly with colon cancer (OR=2.6, 95%CI (1.1–6), p =0.03). However SNP rs224176 was associated with only breast cancer. Conclusion: Our results demonstrate that adiponectin gene SNP rs1501299 and SNP rs224176 may be the predisposing factors in some cancers but our results differ from what has been reported in other populations suggesting a complex relationship between genetic variations and phenotypic adiponectin levels. Show more

Keywords: Adiponectin gene, SNPs, cancer, insulin resistance, adipokines

DOI: 10.3233/DMA-2011-0775

Citation: Disease Markers, vol. 30, no. 4, pp. 197-212, 2011