• Korean Journal of Clinical Laboratory Science
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• v.53 no.3
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• pp.201-207
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• 2021

The 2019 coronavirus outbreak poses a threat to scientific, societal, financial, and health resources. The complex pathogenesis of severe acute respiratory syndrome coronavirus centers on the unpredictable clinical progression of the disease, which may evolve abruptly and result in critical and life-threatening clinical complications. Effective clinical laboratory biomarkers that can classify patients according to risk are essential for ensuring timely treatment, and an analysis of recently published studies found cytokine storm and coagulation disorders were leading factors of severe COVID-19 complications. The following inflammatory, biochemical, and hematology biomarkers markers have been identified in COVID-19 patients; neutrophil to lymphocyte ratio, c-reactive protein, procalcitonin, urea, liver enzymes, lactate dehydrogenase, serum amyloid A, cytokines, d-dimer, fibrinogen, ferritin, troponin, creatinine kinase, and lymphocyte, leukocyte, and platelet counts. These factors are predictors of disease severity and some are involved in the pathogenesis of COVID-19. CRP is an acute-phase, non-specific serological biomarker of inflammation and infection and is related to disease severities and outcomes. In the present study, CRP levels were found to rise dramatically among COVID-19 patients, and our findings suggest CRP could be utilized clinically to predict COVID-19 prognosis and severity even before disease progression and the manifestation of clinical symptoms.

• BMB Reports
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• v.53 no.12
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• pp.664-669
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• 2020

Breast cancer is one of the most frequently diagnosed cancers. Although biomarkers are continuously being discovered, few specific markers, rather than classification markers, representing the aggressiveness and invasiveness of breast cancer are known. In this study, we used samples from canine mammary tumors in a comparative approach. We subjected 36 fractions of both canine normal and mammary tumor plasmas to high-performance quantitative proteomics analysis. Among the identified proteins, LCAT was selectively expressed in mixed tumor samples. With further MRM and Western blot validation, we discovered that the LCAT protein is an indicator of aggressive mammary tumors, an advanced stage of cancer, possibly highly metastatic. Interestingly, we also found that LCAT is overexpressed in high-grade and lymph-node-positive breast cancer in silico data. We also demonstrated that LCAT is highly expressed in the sera of advanced-stage human breast cancers within the same classification. In conclusion, we identified a possible common plasma protein biomarker, LCAT, that is highly expressed in aggressive human breast cancer and canine mammary tumor.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.4
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• pp.299-308
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• 2007

Purpose: The aim of this study was to develop a bioinformatics software and to test it in serum samples of papillary thyroid cancer using mass spectrometry (SELDI-TOF-MS). Materials and Methods: Development of 'Protein analysis' software performing decision tree analysis was done by customizing C4.5. Sixty-one serum samples from 27 papillary thyroid cancer, 17 autoimmune thyroiditis, 17 controls were applied to 2 types of protein chips, CM10 (weak cation exchange) and IMAC3 (metal binding - Cu). Mass spectrometry was performed to reveal the protein expression profiles. Decision trees were generated using 'Protein analysis' software, and automatically detected biomarker candidates. Validation analysis was performed for CM10 chip by random sampling. Results: Decision tree software, which can perform training and validation from profiling data, was developed. For CM10 and IMAC3 chips, 23 of 113 and 8 of 41 protein peaks were significantly different among 3 groups (p<0.05), respectively. Decision tree correctly classified 3 groups with an error rate of 3.3% for CM10 and 2.0% for IMAC3, and 4 and 7 biomarker candidates were detected respectively. In 2 group comparisons, all cancer samples were correctly discriminated from non-cancer samples (error rate = 0%) for CM10 by single node and for IMAC3 by multiple nodes. Validation results from 5 test sets revealed SELDI-TOF-MS and decision tree correctly differentiated cancers from non-cancers (54/55, 98%), while predictability was moderate in 3 group classification (36/55, 65%). Conclusion: Our in-house software was able to successfully build decision trees and detect biomarker candidates, therefore it could be useful for biomarker discovery and clinical follow up of papillary thyroid cancer.

• Biomolecules & Therapeutics
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• v.21 no.3
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• pp.190-195
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• 2013

Cisplatin is a member of platinum-containing anti-cancer drugs that causes cross-linking of DNA and ultimately cancer cell apoptosis. The therapeutic function of cisplatin on various types of cancers has been widely reported but the side effects have been discovered together and nephrotoxicity has been regarded as major side effect of cisplatin. To select candidates for new sensitive nephrotoxicity biomarker, we performed proteomic analysis using 2-DE/MALDI-TOF-MS followed by cisplatin treatment in human kidney cell line, HK-2 cells, and compared the results to the gene profile from microarray composed of genes changed in expression by cisplatin from formerly reported article. Annexin A5 has been selected to be the most potential candidate and it has been identified using Western blot, RT-PCR and cell viability assay whether annexin A5 is available to be a sensitive nephrotoxic biomarker. Treatment with cisplatin on HK-2 cells caused the increase of annexin A5 expression in protein and mRNA levels. Over-expression of annexin A5 blocked HK-2 cell proliferation, indicating correlation between annexin A5 and renal cell toxicity. Taken together, these results suggest the possibility of annexin A5 as a new biomarker for cisplatin-mediated nephrotoxicity.

• Applied Chemistry for Engineering
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• v.32 no.4
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• pp.461-466
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• 2021

In this article, a portable and cost-effective voltammetric biosensor with nanoparticles was developed for the measurements of heterogeneous nuclear ribonucleoprotein A1 protein (hnRNP A1) biomarker which can potentially be used for lung cancer diagnosis. Gold nanoparticles were first electrodeposited onto screen printed carbon electrode (SPCE) followed by immobilizing a single stranded DNA aptamer specific to hnRNP A1 onto the electrode surface. Ethanolamine was also used when immobilizing DNA aptamer on the surface to prevent signals from non-specific adsorption events. Sequential injection of hnRNP A1 biomarker and anti-hnRNP A1 conjugated with alkaline phosphatase (ALP) onto the aptamer chip surface allows to form the sandwich complex of DNA aptamer/hnRNP A1/ALP-anti-hnRNP A1 on the electrode surface which further reacted with 4-aminophenyl phosphate (APP). The electrocatalytic reaction of the enzyme, ALP, and the substrate, APP, resulting in the oxidative current response changes at -0.05 and -0.17 V (vs. Ag/AgCl) against the hnRNP A1 concentration was measured using cyclic and differential pulse voltammetry, respectively. The Au nanoparticles-integrated voltammetric biosensor was applied to analyze human normal serum solutions possibly suggesting potential applicability for lung cancer diagnosis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.101-105
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• 2014

Background and Purpose: Human epididymis protein 4 (HE4) has been suggested to be a novel biomarker of epithelial ovarian cancer (EOC). The present study aimed to evaluate and compare HE4 with the commonly used marker, carbohydrate antigen 125 (CA125), in prediction and therapy-monitoring of EOC. Patients and Methods: Serum HE4 concentrations from 123 ovarian cancer patients and 174 controls were measured by Roche electrochemiluminescent immunoassay (ECLIA). Risk of ovarian malignancy algorithm (ROMA) values were calculated and assessed. In addition, the prospects of HE4 detection for therapy-monitoring were evaluated in EOC patients. Results: The ROMA score could classify patients into high- and low-risk groups with malignancy. Indeed, lower serum HE4 was significantly associated with successful surgical therapy. Specifically, 38 patients with EOC exhibited a greater decline of HE4 compared with CA125. In contrast, elevation of HE4 better predicted recurrence (of 46, 11 patients developed recurrence, and with it increased HE4 serum concentrations) and a poor prognosis than CA125. Conclusions: This study suggests that serum HE4 levels are closely associated with outcome of surgical therapy and disease prognosis in Chinese EOC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6063-6066
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• 2012

Although alteration in the haptoglobin phenotype has been reported in patients with bladder cancer, serum haptoglobin levels have not been evaluated. We hypothesized that serum haptoglobin can be used as a biomarker. The aim of this study was to evaluate the expression of haptoglobin in bladder cancer and to determine the relationship with clinicopathological features. A total of 68 serum specimens obtained before surgery were used to investigate haptoglobin expression using the sandwich ELISA technique. Serum haptoglobin levels were higher in the patients with bladder cancer compared to healthy controls (p<0.0001). Additionally, the levels of haptoglobin protein increased with increasing tumor grades (p<0.001) and were significantly higher in patients with metastatic disease and the presence of lymphovascular involvement, lymph node metastases and increasing tumor burden (p<0.0001). This study suggests that elevated haptoglobin levels are associated with a higher stage, grade, and extent of distant metastasis and larger tumor size. Haptoglobin may therefore provide a useful diagnostic and treatment biomarker for patients with bladder cancer.

• BMB Reports
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• v.41 no.9
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• pp.615-625
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• 2008

Over a last decade, intense interest has been focused on biomarker discovery and their clinical uses. This interest is accelerated by the completion of human genome project and the progress of techniques in proteomics. Especially, cancer biomarker discovery is eminent in this field due to its anticipated critical role in early diagnosis, therapy guidance, and prognosis monitoring of cancers. Among cancers, lung cancer, one of the top three major cancers, is the one showing the highest mortality because of failure in early diagnosis. Numerous potential DNA biomarkers such as hypermethylations of the promoters and mutations in K-ras, p53, and protein biomarkers; carcinoembryonic antigen (CEA), CYFRA21-1, plasma kallikrein B1 (KLKB1), Neuron-specific enolase, etc. have been discovered as lung cancer biomarkers. Despite extensive studies thus far, few are turned out to be useful in clinic. Even those used in clinic do not show enough sensitivity, specificity and reproducibility for general use. This review describes what the cancer biomarkers are for, various types of lung cancer biomarkers discovered at present and predicted future advance in lung cancer biomarker discovery with proteomics technology.

• The Korean Journal of Ecology
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• v.21 no.3
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• pp.225-231
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• 1998

The studies on the potentiality of biomonitoring heavy metal pollution in coastal region of industrial complex were performed to investigate the heavy metal accumulation and induction of metal-binding protein (MBP) as detoxification process using Rumex maritimus. Bioconcentration in organs and MBP in root of R. maritimus was investigated for the research of the tolerance of heavy metals. The bioconcentration of cadmium and zinc in organs showed 3.6-8.0 times in root higher than in shoot, so it was found that heavy metal accumulated selectively in root. MBP increased absorbance in 254 nm and decreased in 280 nm, because it was composed of high cystein content and low aromatic acids, so absorbance had large difference between 254 nm and 280 nm. The existence of MBP in the 10-20 fraction was ascertained with anion exchange chromatography and it was identified that concentration of heavy metal increased according as an exposure concentration of medium increased in QAE Sephadex A-25 elution profile. These results suggested that MBP could play a role in biomarker determining the bioconcentration of plant. This study demonstrated a possibility that removal ability of heavy metal of R. maritimus resulted from detoxification process and MBP could be utilized as a biomarker of heavy metal pollution.

• BMB Reports
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• v.54 no.12
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• pp.601-607
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• 2021

Odorant receptors (ORs) account for about 60% of all human G protein-coupled receptors (GPCRs). OR expression outside of the nose has functions distinct from odor perception, and may contribute to the pathogenesis of disorders including brain diseases and cancers. Glioma is the most common adult malignant brain tumor and requires novel therapeutic strategies to improve clinical outcomes. Here, we outlined the expression of brain ORs and investigated OR expression levels in glioma. Although most ORs were not ubiquitously expressed in gliomas, a subset of ORs displayed glioma subtype-specific expression. Moreover, through systematic survival analysis on OR genes, OR51E1 (mouse Olfr558) was identified as a potential biomarker of unfavorable overall survival, and OR2C1 (mouse Olfr15) was identified as a potential biomarker of favorable overall survival in isocitrate dehydrogenase (IDH) wild-type glioma. In addition to transcriptomic analysis, mutational profiles revealed that somatic mutations in OR genes were detected in > 60% of glioma samples. OR5D18 (mouse Olfr1155) was the most frequently mutated OR gene, and OR5AR1 (mouse Olfr1019) showed IDH wild-type-specific mutation. Based on this systematic analysis and review of the genomic and transcriptomic profiles of ORs in glioma, we suggest that ORs are potential biomarkers and therapeutic targets for glioma.