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Zeitschrift für molekulare Biomarker und Diagnose

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Volumen 3, Ausgabe 4 (2012)

Forschungsartikel

Differential Differentiation- and Survival and Invasion-related T-/Hcadherin (CDH13) Computational Downstream Network from No-Tumor Hepatitis/Cirrhosis (HBV or HCV infection) to Human Hepatocellular Carcinoma (HCC) Malignant Transformation

Lin Wang, Haijing Wu, Minghu Jiang, Juxiang Huang, Hong Lin and Haizhen Diao

We constructed and analyzed the low-and high-expression (fold change ≥2) different-activated and -inhibited T-/H-cadherin (CDH13) downstream network from no-tumor hepatitis/cirrhosis (HBV or HCV infection) to HCC malignant transformation in GEO data set by integration of gene regulatory network inference method based on linear programming and decomposition procedure with GO database. Our results show that the low-expression CDH13 downstream network has the multi-activated and -inhibited molecular pattern in no-tumor hepatitis/cirrhosis, whereas high-expression CDH13 downstream mainly somewhat inhibited molecular connections but significant reduced network (fold ≥2) in HCC. We suppose that the low-expression CDH13 downstream network mainly activates cell differentiation cell adhesion, but inhibits nuclear chromosome, mitosis in no-tumor hepatitis/cirrhosis, whereas the high-expression CDH13 downstream network activates Rab-protein geranylgeranyltransferase activity, protein modification, but inhibits modification-dependent protein catabolism and nucleotide binding in HCC. We put forward hypothesis that low-expression CDH13 activates cadherin binding, homophilic cell adhesion, negative regulation of cell adhesion, positive regulation of calcium-mediated signaling, calcium-dependent cell-cell adhesion, positive regulation of cell-matrix adhesion, low density lipoprotein mediated signaling and inhibits regulation of endothelial cell proliferation, positive regulation of smooth muscle cell proliferation, keratinocyte proliferation, as a result of inducing differentiation in no-tumor hepatitis/cirrhosis, whereas high-expression CDH13 activates positive regulation of survival gene product activity, protein homodimerization activity, Rho protein signal transduction, Rac protein signal transduction, positive regulation of cell migration, sprouting angiogenesis, positive regulation of positive chemotaxis, epidermal growth factor receptor signaling pathway, endothelial cell migration, lamellipodium biogenesis, and inhibits regulation of endocytosis, caveola, as a result of inducing survival and invasion in HCC. Our inferences are consistent with different-activated and -inhibited CDH13 downstream network, GO database and literatures, respectively.

Rezensionsartikel

Expression of YKL-40, an Inflammatory Glycoprotein and its Prognostic Implications in Cancer

Hurmale Anil Kumar, Jatawa Suresh Kumar, Yadav Mahavir and Tiwari Archana

A cancer prognosticator refers to a substance or process that is a sign of the existence of cancer in the body and foretelling the course of cancer. It might be either a molecule oozed by a tumor or it can be a specific response of the body to the occurrence of cancer. YKL-40 is an inflammatory glycoprotein and a member of mammalian chitanaselike proteins (CHI3L1), is expressed and secreted by several types of solid tumor cells, inflammatory cells and stem cells. The precise physiological role of YKL-40 in cancer is not still clear and suggested that it has a role in cancer cell proliferation, differentiation, metastatic potential, cell attachment and migration, reorganization and tissue remodeling. Several clinical studies of patients with diverse types of cancer indicated that elevated serum level of YKL-40 may be a prognostic marker of cancer. The higher level of YKL-40 in serum also seems to correlate with short survival and poorer prognosis of several cancers including breast, ovary, colorectal, and glioblastoma melanoma. Serum YKL-40 level is often elevated compared to healthy subjects, in patients with disease characterized by inflammation, and increased extracellular remodeling or ongoing fibrosis such as infections. This review depict the present facts regarding YKL-40 and talk about its relation in cancer prediction

Rezensionsartikel

Overcoming the Deficiency of Singular Detection by Antibody Arrays in Cancer Biomarker Discovery

Weidong Jiang and Ruo-Pan Huang

Since cancer is a heterogeneous disease, it is unlikely that a single biomarker will detect all cancers of a particular organ with high specificity and sensitivity. Thus, detection of expression of multiple proteins is essential to unraveling the mechanisms and effects of carcinogenesis. Antibody arrays have been developed to meet this growing demand. The ability to simultaneously measure the expression profiling of multi-protein markers will provide a powerful platform for identification of new cancer biomarkers. In this review, we will discuss the planar format of antibody array technology, its suitability and challenges for cancer biomarker discovery, and examples of its applications for biomarker discovery and validation in a wide variety of human cancers

Forschungsartikel

Serum and Saliva Levels of High-Sensitivity C-reactive Protein in Acute Myocardial Infarction

Iraj Mirzaii-Dizgah, Esmail Riahi and Reza Miri

Objective: The aim of this study was to evaluate the serum and saliva levels of high-sensitivity C-reactive protein (hs-CRP) in the patients with acute myocardial infarction (MI). Materials and Methods: In a cross sectional study, 28 patients with acute MI and 28 healthy subjects were recruited to the study, and hs-CRP levels which were measured in the serum, resting saliva, and stimulated saliva at the morning of first and second days of acute MI using ELISA method. Statistical analysis of the Student’s t test and Pearson correlation coefficient were used. Results: The mean stimulated saliva hs-CRP concentration (ng/ml) was significantly higher in the patients with acute MI at both the first and the second day of MI (2.08 ± 0.55 and 2.78 ± 0.75 respectively) than in the control group (0.26 ± 0.11). It was also higher in unstimulated saliva in the patients at the both days (3.75 ± 0.92 and 2.78 ± 0.75) than controls (0.68 ± 0.21). Serum hs-CRP level (μg/ml) was higher in the patients at the second day of MI (7.03 ± 0.36) compared to healthy individuals (3.84 ± 0.60). Furthermore, stimulated and unstimulated saliva hs-CRP levels correlated significantly with serum hs-CRP level (r = 0.249, P = 0.044; r = 0.289, P = 0.038 respectively). Conclusion: It can be concluded that saliva level of hs-CRP shows a massive rise after occurrence of acute MI, and salivary hs-CRP may serve as a point-of-care testing for detection of acute MI.

Schnelle Kommunikation

Analysis of Total Urine Proteins: Towards a Non-Invasive Approach for Diagnosis of Visceral Leishmaniasis

Om Prakash Singh and Shyam Sundar

Diagnosis of Visceral Leishmaniasis (VL) is a major obstacle in the control of this disease, as demonstration of parasite by splenic or bone-marrow aspiration is almost impossible in the peripheral rural areas because of lack of facilities. In order to identify a non-invasive biomarker for VL, we employed two-dimensional electrophoresis (2D-PAGE) coupled with mass spectrometry through a comparison of urinary proteome. Though, we did not find the biomarker protein for VL, our findings provide some basic insights for future development of non invasive diagnostic tool.

Forschungsartikel

MITF Expression in Cutaneous Malignant Melanoma

Margrét Agnarsdóttir, Fredrik Ponten, Hans Garmo, Gunnar Wagenius, Lorelei Mucci, Kristina Magnusson, Lars Holmberg and Sonja Eaker-Fält

The MITF protein has a central role in the differentiation and survival of melanocytes. The aim of the study was to investigate whether MITF can be employed as a prognostic marker in patients operated on for cutaneous malignant melanoma. A cohort study design, based on information collected from population-based registries, was employed. For included patients (n=264) tissue microarrays were stained with immunohistochemistry to study the protein expression of MITF in primary malignant melanoma tumors by estimating the fraction of positive tumor cells and the staining intensity. Most of the tumors (84%) expressed MITF in >25% of the tumor cells and for 87% of the tumors the staining intensity was strong. Tumors with cell fraction >75% had a better prognosis compared with those with <75% (HR 0.44, 95% CI: 0.20-1.0, P=0.05). Tumors with a strong staining intensity tended to have a better prognosis compared with the weaker staining ones (HR 0.59, 95% CI: 0.26 -1.36, P=0.22). When cell fraction and intensity were combined, a high-risk group dying of malignant melanoma was identified as those patients with 25- 75% of tumor cells staining with weak intensity (HR 2.9, 95% CI: 0.94-8.7, P=0.06) and those with <25% of tumor cells staining with strong intensity (HR 2.5, 95% CI: 1.1- 6.1, P=0.04). However, the majority of deaths occurred in the lower risk groups. In conclusion, a high-risk group for death in malignant melanoma was identified but MITF is not suitable as a prognostic marker due to the distribution of that particular expression in the population.

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