• 대한임상검사과학회지
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• 제53권3호
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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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• 제53권12호
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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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• 제41권4호
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• pp.299-308
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• 2007

본 연구의 목적은 의사결정트리를 생성하는 생물정보학 프로그램을 개발하고, 이를 갑상선유두암 혈청의 질량분석자료로 시험해 보는 것이다. 대상 및 방법: C4.5를 커스터마이징하여 의사결정트리 분석을 수행할 수 있는 'Protein analysis'라는 프로그램을 개발하였다 61개의 혈청시료(갑상선유두암 27, 자가면역성 갑상선염 17, 대조군 17)를 일정 기간 동안 순차적으로 냉동한 후 실온에서 일시에 해동하여 분석에 사용하였다. 모든 시료는 탈지질화 과정을 거쳐 준비한 후, 2종류의 단백질칩(CM10, IMAC3)에 각각 60개, 50개 시료를 적용하였다. 갑상선유두암의 특징적인 단백질 패턴을 찾기 위해 질량분석기를 이용하여 단백질칩을 분석했다. 'Protein analysis' 프로그램을 이용하여 단백질분포 자료로부터 의사결정트리를 작성하고, 생체표지자 후보물질을 검출하였다. CM10칩에서 발견된 생체표지자 후보물질을 무작위 표본추출 방법을 이용하여 검증하였다. 결과: 단백질분포 자료의 훈련과 검증이 가능한 의사결정트리 프로그램이 개발되었으며, 이 프로그램은 트리 구조와 노드 정보, 트리 구성 과정을 표시하는 3개의 창으로 구성되었다. CM10칩을 이용한 분석에서 총 113개의 단백질 피크 중 23개가 3그룹 간에 유의한 차이가 있었으며, IMAC3는 41개의 단백질 피크 중 8개가 3그룹 간에 유의한 차이가 있었다. 3그룹 분석에서 의사결정트리는 CM10칩과 IMAE3의 단백질분포 자료로부터 각각 60개와 50개의 시료를 높은 정확도로 분류하였으며(오차율 = 각각 3.3%, 2.0%), 각각 4개와 7개의 생체표지자 후보물질을 검출하였다. 암시료와 비암시료를 구분하는 2그룹 분석 에서, 의사결정트리는 모든 암시료를 정확히 구분하였으며(모두 오차율 = 0%), CM10칩을 이용한 분석에서는 단일 노드를 사용하고, IMAC3칩을 이용한 분석에서는 여러 개의 노드를 사용하였다. CM10칩의 단백질 분포자료를 5번의 무작위 추출에 의해 시행한 검증에서 암시료와 비암시료를 구분하는데 높은 정확도를 보였으나(정확도 = 98%, 54/55), 3그룹을 구분할 때는 중등도의 정확도를 보였다(정확도 = 65%, 36/55). 결론: 우리가 개발한 프로그램은 질량분석 자료로부터 성공적으로 의사결정트리를 생성하고, 생체표지자 후보물질을 검출할 수 있었다. 따라서 이 프로그램은 혈청 시료를 이용한 생체표지자 발굴 및 갑상선유두암의 추적관찰에 유용하게 사용될 수 있을 것이다.

• Biomolecules & Therapeutics
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• 제21권3호
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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.

• 공업화학
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• 제32권4호
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• pp.461-466
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• 2021

본 논문에서는 이동성이 좋고 경제적이며, 간편하게 일회용 진단칩으로 제작 가능한 스크린 프린팅 한 탄소칩 전극[screen printed carbon electrode (SPCE)] 기반의 전압전류법 나노물질 융합형 바이오센서를 제작하여 폐암 조기진단에 활용 가능한 단백질 표지 인자 중에 하나인 heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) 단백질의 농도를 정량 분석하고자 하였다. 먼저 SPCE 표면에 금 나노입자를 전기적으로 증착한 후 크로스링커를 이용하여 hnRNP A1에 특이적으로 결합할 수 있는 바이오리셉터인 DNA 압타머를 고정하였다. Ethanolamine을 블로킹 시약으로 사용하여 압타머와 함께 센서 표면에 고정하여 그 표면을 처리함으로써 비특이적인 생물질의 흡착에 의한 방해 신호를 최소화하고자 하였다. DNA칩과 hnRNP A1 용액을 접촉하여 DNA와 hnRNP A1을 결합시킨 후 alkaline phosphatase (ALP) 효소로 접합한 hnRNP A1 항체(anti-hnRNP A1)을 센서칩 표면으로 주입하여 샌드위치 복합체를 형성하고, 이를 기질인 4-aminophenyl phosphate (APP)와 효소-기질 특이적 산화 반응에 의한 전류 변화를 순환 전압전류법과 시차 펄스전압전류법으로 측정하여 단백질의 농도를 정량적으로 분석하였다. 상기 산화 반응에 의한 피크 전류 변화는 순환전압전류법과 시차 펄스 전압전류법을 사용할 때 -0.05와 -0.17 V (vs. Ag/AgCl) 전위 값에서 각각 일어났다. 개발한 나노바이오센서를 실제 정상인 혈청 시료 분석에 적용 가능함을 보여줌으로써 혈청 한 방울로 폐암의 조기진단 가능성을 제시하고자 하였다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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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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• 제13권12호
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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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• 제41권9호
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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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• 제21권3호
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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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• 제54권12호
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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.