• Korean Journal of Clinical Laboratory Science
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• v.51 no.1
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• pp.26-33
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• 2019

Recently, the rapid growth of the companion animal market has led to the development of animal disease diagnosis kits. Therefore, the utility of the introduction of biomarkers for the development of animal molecular diagnostics is being reevaluated. A good biomarker should be precise and reliable, distinguish between normal and diseased states, and differentiate between different diseases. Recently reported genetic markers, tumor markers (cell free DNA, circulating tumor cells, granzyme, and skin tumors), and others (brucellosis, programmed death recovery-1, symmetric dimethylarginine, periostin, and cysteinyl leukotrien) have been developed. The biomarkers are used for risk prediction or for the screening, diagnosis, and monitoring of disease progression. The most important criteria for related biomarkers are disease specificity. Many potential biomarkers have emerged from laboratory and test studies, but they have not been validated in independent or large-scale clinical studies. Candidate biomarkers evaluate disease associations, verify the effectiveness of biomarkers for early detection and disease progression, and incorporate them into humans and animals. In the future, it will be necessary to reevaluate the utility of well-structured biomarker-based research and study the development of kits that can be used in on-site tests in accordance with the trends introduced in the diagnosis of animal diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4541-4544
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• 2012

Background: Breast cancer is the most common malignancy with the highest incidence rates among women worldwide. Triple-negative breast cancer (TNBC) disease is diagnosed more frequently in younger women, and is associated with a poor prognosis. Elevated levels of serum haptoglobin protein (Hp) are observed in many malignant diseases including breast cancer. We evaluated the expression and prognostic value of Hp among patients with TNBC. Materials and Methods: Serum Hp levels were determined by Elisa in 41 patients with TNBC and 10 normal individuals. Hp status was correlated with other clinico-pathological parameters including patient survival. Results: Of the 41 patients with TNBC, Hp over expression was detected in 24 (59%) by Elisa. Hp up-regulation was confirmed by Elisa based quantification in the serum of 41 TNBC patients against lower grades and 10 normal individuals. Survival analysis revealed that Hp ($p=2.016{\times}10^{-5}$), stage ($p=2.166{\times}10^{-5}$), distant metastasis ($p=2.217{\times}10^{-5}$), tumor size ($p=1.053{\times}10^{-5}$), and tumor grade (p=0.001), correlated with patient survival on univariate analysis. Multivariate analysis revealed that Hp (p=0.001), and grade of the disease (p=0.008) were independent predictors of survival. Conclusion: Our results indicate that serum levels of Hp may play a role as a potential serum biomarker and prognostic indicator among TNBC patients. Thus, Hp may present a new promising prognostic biomarker in TNBC patients, but independent validations are now necessary for confirmation.

• Tuberculosis and Respiratory Diseases
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• v.75 no.3
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• pp.104-110
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• 2013

Background: Osteopontin (OPN) and carbonic anhydrase IX (CAIX), which are expressed on the surface of tumor cells, are associated with hypoxia during tumor development and progression. However, the roles of these proteins in the plasma of patients with non-small cell lung cancer (NSCLC) are poorly understood. Herein, we hypothesized that plasma OPN and CAIX levels could be used as diagnostic and prognostic tumor markers in patients with NSCLC. Methods: Fifty-three patients with NSCLC and 50 healthy control subjects were enrolled. We selected controls without malignancy and matched them with NSCLC patient cases according to age and gender. Blood samples were collected at the time of diagnosis; the plasma levels of OPN and CAIX were measured by enzyme-linked immunosorbent assays. Results: The plasma levels of OPN in the patients with NSCLC were significantly elevated as compared to those in the controls (p=0.016). However, there was no difference in the plasma level of CAIX between the NSCLC patients and controls. NSCLC patients with a distant metastasis had a remarkable increase in plasma OPN compared with patients without metastasis (p=0.026), but no such correlation was found for CAIX. There was no difference in overall survival rates according to the plasma level of OPN between the two groups (by Kaplan-Meier survival analysis). Conclusion: Plasma OPN levels were elevated in patients with NSCLC as compared with the controls, with greater elevation of OPN levels in the advanced stages of disease. Therefore, plasma OPN may have utility as a diagnostic, but not prognostic, biomarker of advanced NSCLC.

• Parasites, Hosts and Diseases
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• v.48 no.2
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• pp.127-132
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• 2010

Biomphalaria alexandrina snails play an indispensable role in transmission of schistosomiasis. Infection rates in field populations of snails are routinely determined by cercarial shedding neglecting prepatent snail infections, because of lack of a suitable method for diagnosis. The present study aimed at separation and quantification of oxalic, malic, acetic, pyruvic, and fumaric acids using ion-suppression reversed-phase high performance liquid chromatography (HPLC) to test the potentiality of these acids to be used as diagnostic and therapeutic biomarkers. The assay was done in both hemolymph and digestive gland-gonad complex (DGG) samples in a total of 300 B. alexandrina snails. All of the studied acids in both the hemolymph and tissue samples except for the fumaric acid in hemolymph appeared to be good diagnostic biomarkers as they provide not only a good discrimination between the infected snails from the control but also between the studied stages of infection from each other. The most sensitive discriminating acid was malic acid in hemolymph samples as it showed the highest F-ratio. Using the Z-score, malic acid was found to be a good potential therapeutic biomarker in the prepatency stage, oxalic acid and acetic acid in the stage of patency, and malic acid and acetic acid at 2 weeks after patency. Quantification of carboxylic acids, using HPLC strategy, was fast, easy, and accurate in prediction of infected and uninfected snails and possibly to detect the stage of infection. It seems also useful for detection of the most suitable acids to be used as drug targets.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10433-10438
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• 2015

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children and represents approximately 25% of cancer diagnoses among those younger than 15 years of age. Aim and Objectives: This study investigated substitutions in the ATP synthase subunit 6 gene of mitochondrial DNA (mtDNA) as a potential diagnostic biomarker for early detection and diagnosis of acute lymphoblastic leukemia. Based on mtDNA from 23 subjects diagnosed with acute lymphoblastic leukemia, approximately 465 bp of the ATP synthase subunit 6 gene were amplified and sequenced. Results: The sequencing revealed thirty-one mutations at 14 locations in ATP synthase subunit 6 of mtDNA in the ALL subjects. All were identified as single nucleotide polymorphisms (SNPs) with a homoplasmic pattern. The mutations were distributed between males and females. Novel haplotypes were identified in this investigation: haplotype (G) was recorded in 34% in diagnosed subjects; the second haplotype was (C) with frequency of 13% in ALL subjects. Neither of these were observed in control samples. Conclusions: These haplotypes were identified for the first time in acute lymphoblastic leukemia patients. Five mutations able to change amino acid synthesis for the ATP synthase subunit 6 were associated with acute lymphoblastic leukemia. This investigation could be used to provide an overview of incidence frequency of acute lyphoblastic leukemia (ALL) in Saudi patients based on molecular events.

• Korean Journal of Biological Psychiatry
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• v.19 no.1
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• pp.29-37
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• 2012

The loudness dependence of the auditory evoked potential (LDAEP) has been proposed as a valid biomarker of central serotoninergic activity in humans. The specificity and sensitivity of the LDAEP to changes in serotonergic neurotransmission have recently been explored in many studies about pharmacology and genetics. The majority of evidence for an association between the LDAEP and serotonin activity has come from animal studies. Genetic association studies with the LDAEP have provided conflicting reports with additional evidence outlining sensitivity to other neurotransmitter systems including the dopamine and glutamatergic systems. The LDAEP has been revealed to reflect the pathophysiology of various psychiatric illnesses. There is supporting evidence that major psychiatric disorders have differential LDAEP activities. Overall, the LDAEP shows strong evidence as a potential predictor of antidepressant treatment response. It need to be explored whether the LDAEP could be a biological marker of various psychiatric diseases and treatment prediction of antidepressants and serotonin related drugs.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6527-6531
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• 2012

Purpose: Complement receptor 1 (CR1) is induced by Epstein-Barr virus (EBV) and may be a potential biomarker of nasopharyngeal carcinoma (NPC). We conducted the present study to evaluate the association of CR1 expression with clinicopathological features and prognosis of NPC. Methods: We enrolled 145 NPC patients and 110 controls. Expression levels of CR1 in peripheral blood mononuclear cells (PBMCs) were detected using quantitative real-time PCR and associations with clinicopathological features and prognosis were examined. Results: CR1 levels in the NPC group [3.54 (3.34, 3.79)] were slightly higher than those in the controls [3.33 (3.20, 3.47)] (P<0.001). Increased CR1 expression was associated with histology classification (type III vs. type II, P=0.002), advanced clinical stage (P=0.003), high T stage (P=0.017), and poor overall survival (HR, 4.89; 95% CI, 1.23-19.42; P=0.024). However, there were no statistically significant differences in CR1 expression among N or M stages. Conclusion: These findings indicate that CR1 expression in PBMCs may be a new biomarker for prognosis of NPC and a potential therapeutic target.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.201-205
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• 2016

Cholangiocarcinoma (CCA) is generally a rare primary liver tumor of the bile duct with extremely poor clinical outcomes due to late diagnosis. Osteopontin (OPN) is the most abundant expressed gene in intrahepatic CCA and its involvement in tumor aggressiveness suggests it could be a useful prognostic biomarker. However, the prognostic significance of OPN expression in CCA is still controversial. We therefore immunohistochemically studied OPN expression in 354 resected CCAs and correlated the results with patient clinicopathological parameters. OPN expression was separately scored according to the percentage of cancer cells or degree of stromal tissue staining and classified as low (score 0-1) and high (score 2-3). OPN expression in CCA cells was found in 177 out of 354 patients (56.5%), whereas stroma was positive in 185 out of 354 patients (52.3%). Univariate analysis with several of the aforementioned parameters revealed that stromal but not cancer cell OPN expression was significantly associated with tumor size, tumor direct invasion into normal liver parenchyma, regional lymph node metastasis and higher staging. The combination of cancer cell and stromal OPN expression demonstrated a positive trend for linkage with lymph node metastasis. Multivariate analysis identified gender, the presence of lymphatic permeation and lymph node metastasis, but not OPN expression, as independent prognostic factors. This study confirms the presence of stromal OPN expression in tumor aggressiveness but not survival in CCA patients.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4833-4837
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• 2015

Biomarkers for preclinical diagnosis of cancer are valuable tools for detection of malignant tumors at early stages in groups at risk and screening healthy people, as well as monitoring disease recurrence after treatment of cancer. However the complexity of the body's response to the pathological processes makes it virtually impossible to evaluate this response to the development of the disease using a single biomarker that is present in the serum at low concentrations. An alternative approach to standard biomarker analysis is called immunosignature. Instead of going after biomarkers themselves this approach rely on the analysis of the humoral immune response to molecular changes associated with the development of pathological processes. It is known that antibodies are produced in response to proteins expressed during cancer development. Accordingly, the changes in antibody repertoire associated with tumor growth can serve as biomarkers of cancer. Immunosignature is a highly sensitive method for antibody repertoire analysis utilizing high density peptide microarrays. In the present review we discuss modern methods for antibody detection, as well as describe the principles and applications of immunosignature in research and clinical practice.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5779-5785
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• 2015

The present study was designed to investigate cholangiocarcinoma (CCA) antibodies in hamster serum. Hamster CCA cell lines were processed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. A candidate biomarker was confirmed by immunoprecipitation and western blot, and was further analyzed using ELISA and sera from normal control hamsters, hamsters with opisthorchiasis and hamsters with various stages of CCA, as well as from CCA patients and healthy individuals. One candidate marker was identified as $HSP90{\alpha}$, as indicated by a high level of anti-$HSP90{\alpha}$ in hamster CCA sera. It was found that the levels of anti-$HSP90{\alpha}$ were specifically elevated in the sera of hamsters with CCA compared with other groups and progressively increased with the clinical stage. At the cut-off point of 0.4850 on the receiver operating characteristic curve, anti-$HSP90{\alpha}$ could discriminate CCA from healthy control groups with a sensitivity of 76.2%, specificity of 71.4% and total accuracy 75.5%. In the present study, we have shown that anti-$HSP90{\alpha}$ may be a potential useful serum biomarker to discriminate CCA cases from healthy persons.