Disease Markers - Volume 32, issue 4

Authors: Nachmany, Henny | Wald, Shane | Abekasis, Michal | Bulvik, Shlomo | Weil, Miguel

Article Type: Research Article

Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative disorder caused by degeneration of motor neurons. The cause for most cases of ALS is multi-factorial,this enhances the need to characterize and isolate specific biomarkers found in biological samples from ALS patients. To this end we use human mesenchymal stem cells (hMSC) derived from the bone marrow of six ALS patients (ALS hMSC) and identified two genes, Cytoplasmic FMR Interacting Protein 2 (CyFIP2) and Retinoblastoma (Rb) Binding Protein …9 (RbBP9) with a significant decrease in post transcriptional A to I RNA editing compared to hMSC of healthy individuals. At the transcriptional level we show abnormal expression of these two genes in ALS hMSC by quantitative real time-PCR (qRT-PCR) and Western blot suggesting a problem in the regulation of these genes in ALS. To strengthen this view we tested by qRT-PCR the expression of these genes in peripheral blood leukocytes (PBL) isolated from blood samples of 17 ALS patients and found that CyFIP2 and RbBP9 levels of expression were significantly different compared to the levels of expression of these two genes in 19 normal PBL samples. Altogether we found two novel ALS potential biomarkers in non-neural tissues from ALS patients that may have direct diagnostic and therapeutic implications to the disease. Show more

Keywords: ALS biomarkers, CyFIP2, RbBP9, human mesenchymal stem cells, leukocytes

DOI: 10.3233/DMA-2011-0885

Citation: Disease Markers, vol. 32, no. 4, pp. 211-220, 2012

Authors: Molina-Pinelo, Sonia | Suárez, Rocío | Pastor, María Dolores | Nogal, Ana | Márquez-Martín, Eduardo | Martín-Juan, José | Carnero, Amancio | Paz-Ares, Luis

Article Type: Research Article

Abstract: The identification of new less invasive biomarkers is necessary to improve the detection and prognostic outcome of respiratory pathological processes. The measurement of miRNA expression through less invasive techniques such as plasma and serum have been suggested to analysis of several lung malignancies including lung cancer. These studies are assuming a common deregulated miRNA expression both in blood and lung tissue. The present study aimed to obtain miRNA representative signatures both in plasma and …bronchoalveolar cell fraction that could serve as biomarker in respiratory diseases. Ten patients were evaluated to assess the expression levels of 381 miRNAs. We found that around 50% miRNAs were no detected in both plasma and bronchoalveolar cell fraction and only 20% of miRNAs showed similar expression in both samples. These results show a lack of association of miRNA signatures between plasma and bronchoalveolar cytology in the same patient. The profiles are not comparable; however, there is a similarity in the relative expression in a very small subset of miRNAs (miR-17, miR-19b, miR-195 and miR-20b) between both biological samples in all patients. This finding supports that the miRNAs profiles obtained from different biological samples have to be carefully validated to link with respiratory diseases. Show more

Keywords: miRNA profile, RT-qPCR, plasma and bronchoalveolar fluid cytology, respiratory disease

DOI: 10.3233/DMA-2011-0882

Citation: Disease Markers, vol. 32, no. 4, pp. 221-230, 2012

Authors: Esparragón, Francisco Rodríguez | Companioni, Osmel | Bello, Miguel García | Ríos, Nisa Buset | Pérez, José Carlos Rodríguez

Article Type: Research Article

Abstract: Recent genome-wide single nucleotide polymorphism (SNP) association studies (GWAS) have identified a number of SNPs that were significantly associated with coronary artery disease (CAD) and myocardial infarction (MI). We tested for replication of the previously described association with CAD in our case-control datasets of SNPs variants located at 1p13.1, 2q33.1, 10q11.1, 9p21, and 21q22. We observed a small significant risk associated of the SNP rs10757274 with CAD in the PROCAGENE study. Besides, the multilocus combination …rs10757274 and rs1333048 gave a near significant result. We confirmed that the SNP rs10757274 showed association with CAD in the PROCAGENE study, although after applying the Bonferroni correction was not longer significant. Independent replication studies in other populations are needed to unequivocally confirm the association. Show more

Keywords: Genome-wide association studies, polymorphisms, coronary artery disease, myocardial infarction

DOI: 10.3233/DMA-2011-0879

Citation: Disease Markers, vol. 32, no. 4, pp. 231-239, 2012

Authors: Tabaripour, Reza | Niaki, Haleh Akhavan | Douki, Mohammad Reza Esmaeeli | Bazzaz, Javad Tavakkoly | Larijani, Bagher | Yaghmaei, Parichehr

Article Type: Research Article

Abstract: Background: Cystic fibrosis is a monogenic recessive disorder found predominantly in Caucasian population. This disease arises from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In this study we consider poly T polymorphism c.1210-12T[5], c.1210-12T[7], c.1210-12T[9] (T_{5} , T_{7} , T_{9} ) in the intron 8 of CFTR gene in normal individuals and cystic fibrosis patients in the north of Iran. Material and methods: 40 CF patients and 40 normal individuals were screened …for poly T polymorphism in intron 8 of CFTR gene using Reverse Dot Blot method which was also used to detect p.Phe508del among CF patients. Results: T_{7} allele is the most prevalent in both normal and CF patients. Its abundance is approximately 75%. T_{9} and T_{5} represent approximately 20% and 5% of alleles respectively. T_{7} / T_{7} genotype is the most present in both normal and CF patients with 72.5% and 60% prevalence respectively. p.Phe508del was present in 13 CFTR alleles belonging to 7 patients with either homozygote T_{9} / T_{9} , T_{7} / T_{7} or compound heterozygote T_{7} / T_{9} genotypes. Conclusion: Contrary to the Caucasians, T_{7} allele is more frequent in Northern Iranian CF patients. The presence of p.Phe508del and T_{7} allele in the same framework is reported for the first time in this part of the world. Further investigations of other populations will help to understand whether p.Phe508del arose by selection pressure in this part of the world or was imported from European countries. The abundance of T_{5} , T_{7} , T_{9} alleles indicates that this polymorphism can be used as one of the informative markers for detection of normal and mutant alleles in prenatal diagnosis or carrier assessment in families with previous history of the disease in regions with high degree of CFTR mutation heterogeneity. Show more

Keywords: Cystic fibrosis, IVS8 polyT, polymorphism, p.Phe508del, Iran

DOI: 10.3233/DMA-2011-0880

Citation: Disease Markers, vol. 32, no. 4, pp. 241-246, 2012

Authors: Chiabai, Marcela A. | Lins, Tulio C.L. | Pogue, Robert | Pereira, Rinaldo W.

Article Type: Research Article

Abstract: This study aimed to evaluate in the Brazilian population, the genotypes and population frequencies of pharmacogenetic polymorphisms involved in the response to drugs used in treatment of acute lymphoblastic leukemia (ALL), and to compare the data with data from the HapMap populations. There was significant differentiation between most population pairs, but few associations between genetic ancestry and SNPs in the Brazilian population were observed. AMOVA analysis comparing the Brazilian population to all other populations …retrieved from HapMap pointed to a genetic proximity with the European population. These associations point to preclusion of the use of genetic ancestry as a proxy for predicting drug response. In this way, any study aiming to correlate genotype with drug response in the Brazilian population should be based on pharmacogenetic SNP genotypes. Show more

Keywords: SNPs, Brazilian population, pharmacogenetic polymorphisms, HapMap

DOI: 10.3233/DMA-2011-0884

Citation: Disease Markers, vol. 32, no. 4, pp. 247-253, 2012

Authors: El-Tayeh, Sarmad F. | Hussein, Tarek D. | El-Houseini, Motawa E. | Amer, Mahmoud A. | El-Sherbini, Mamdooh | Elshemey, Wael M.

Article Type: Research Article

Abstract: Hepatocellular carcinoma (HCC) is one of the most aggressive cancers worldwide. In Egypt, the disease is usually detected in an advanced stage at which no treatment may be effective including surgery. Early detection of the disease is thus an important goal allowing the patient to be treated before the enlargement of the tumor or its metastasis to distant organs. Tumor markers are serological agents which serum level may be useful in predicting the presence of the …tumor at early stages. Alpha fetoprotein (AFP) which is the golden marker for HCC is of low sensitivity, therefore, additional markers such as alpha-L-fucosidase (AFU), transforming growth factors alpha and beta (TGF-α and TGF-β) and interleukin-8 (IL-8) are suggested to be simultaneously evaluated in order to enhance the detection of HCC. A total of 96 patients with different liver diseases such as HCC, hepatitis C virus (HCV), hepatitis B virus (HBV) and cirrhotic patients are included in this study. Sixteen healthy volunteers are used as a control group. In patients with HCC each of AFP, AFU, TGF-α and TGF-β recorded significantly higher levels than the other patient groups and controls. HCC patients recorded significantly lower level of IL-8 compared to the other patient groups but significantly higher than the control. For AFP, AFU, TGF-α, TGF-β and IL-8, at the optimal cut-off values (obtained from the receiver operating characteristic (ROC) curves), the calculated sensitivities are 46%, 72.97%, 67.56%, 54.05% and 83.8%, respectively. The simultaneous evaluation using all of the suggested markers resulted in increasing the sensitivity up to 100%. It thus recommended that, if patients with cirrhosis, as high risk patients, are subjected to regular examination using these markers in addition to AFP, HCC may be detected by 100% sensitivity in an early stage and as a consequence an effective treatment can be achieved. Show more

Keywords: AFP, AFU, TGF-α, TGF-β, IL-8, HCC, HCV, biomarkers

DOI: 10.3233/DMA-2011-0883

Citation: Disease Markers, vol. 32, no. 4, pp. 255-263, 2012

Authors: Zhang, Guoxin | Ha, Seon-Ah | Kim, Hyun K. | Yoo, Jinah | Kim, Sanghee | Lee, Youn S. | Hur, Soo Y. | Kim, Yong W. | Kim, Tae E. | Park, Yong G. | Wang, Jing | Yang, Yang | Xu, Zekuan | Song, Eun Y. | Huang, Zuhu | Jirun, Peng | Zhongtian, Jin | Shishi, Qiao | Zhuqingqing, Cui | Lei, Gong | Kim, Jin W.

Article Type: Research Article

Abstract: Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors in the world. The only serological marker widely used for the diagnosis of HCC is alpha-fetoprotein (AFP). Despite that AFP is widely used for the diagnosis of HCC, it has a limit as a serological marker due to its low sensitivity and specificity. The human cervical cancer proto-oncogene 1 (HCCR-1) was previously reported as a new biomarker for HCC. To further evaluate the HCCR-1 as …a biomarker for HCC, we conducted the prospective cohort study. We evaluated the significance of simultaneous measurement of 2 tumor markers in the diagnosis of HCC in China, Japan and Korea. Two markers for HCC, AFP and HCCR-1, were measured in the sera obtained from 1,338 patients at the time of initial diagnosis of HCC. Of the 1338 HCC patients, 616 (46%) and 686 (51.3%) were sero-positive for AFP and HCCR-1, respectively. The positive rate for HCC was increased up to 74.1% in combined use of AFP and HCCR-1. Many cases (54%) for AFP-negative HCC were positive for HCCR-1 and vice versa. More importantly, the diagnostic rate for small HCC (< 2 cm) was significantly improved in the combined analysis of AFP and HCCR-1 to 56.9% although it was only 40.1% and 23.4% in the single analysis of HCCR-1 and AFP, respectively. Our result suggests that the HCCR-1 could be an useful biomarker for HCC while the diagnostic rate could be significantly improved in the combined use of HCCR-1 and AFP. Show more

Keywords: Hepatocellular carcinoma, biomarker, AFP, HCCR-1

DOI: 10.3233/DMA-2011-0878

Citation: Disease Markers, vol. 32, no. 4, pp. 265-271, 2012

Authors: Baba, Rafia A. | Bhat, Hina F. | Wani, Lateef A. | Bashir, Muneesa | Wani, Mudasir M. | Qadri, Sumyra K. | Khanday, Firdous A.

Article Type: Research Article

Abstract: The expression of E3B1/ABI-1 protein and its role in cancer progression and prognosis are largely unknown in the majority of solid tumors. In this study, we examined the expression pattern of E3B1/ABI-1 protein in histologically confirmed cases of esophageal (squamous cell carcinoma and adenocarcinoma), gastro-esophageal junction, colorectal cancers and corresponding normal tissues freshly resected from a cohort of 135 patients, by Western Blotting and Immunofluorescence Staining. The protein is present in its …phosphorylated form in cells and tissues. Depending on the extent of phosphorylation it is either present in hyper-phosphorylated (M. Wt. 72 kDa) form or in hypo-phosphorylated form (M. Wt. 68 kDa and 65 kDa). A thorough analysis revealed that expression of E3B1/ABI-1 protein is significantly decreased in esophageal, gastro-esophageal junction and colorectal carcinomas irrespective of age, gender, dietary and smoking habits of the patients. The decrease in expression of E3B1/ABI-1 was consistently observed for all the three isoforms. However, the decrease in the expression of isoforms varied with different forms of cancers. Down-regulation of E3B1/ABI-1 expression in human carcinomas may play a critical role in tumor progression and in determining disease prognosis. Show more

Keywords: Eps8 binding protein, abelson interactor protein, signal transduction, esophageal squamous cell carcinoma, adenocarcinoma, colorectal cancers

DOI: 10.3233/DMA-2011-0881

Citation: Disease Markers, vol. 32, no. 4, pp. 273-279, 2012