• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1339-1344
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• 2014

Aims: Alterations in mitochondrial DNA (mtDNA) have been implicated in carcinogenesis and tumor progression. We here evaluated the diagnostic and prognostic potential of mtDNA as a biomarker for breast cancer. Methods: Using multiplex real-time polymerase chain reaction, nuclear DNA (nDNA) and mtDNA levels in serum, buffy coat, tumor, and tumor-adjacent tissue samples from 50 breast cancer patients were determined and assessed for associations with clinicopathological features. To evaluate mtDNA as a biomarker for distinguishing between the four sample types, we created receiver operating characteristic (ROC) curves. Results: The mtDNA levels in buffy coat were significantly lower than in other sample types. Relative to tumor-adjacent tissue, reduced levels of mtDNA were identified in buffy coat and tumor tissue but not in serum. According to ROC curve analysis, mtDNA levels could be used to distinguish between buffy coat and tumor-adjacent tissue samples with good sensitivity (77%) and specificity (83%). Moreover, mtDNA levels in serum and tumor tissue were positively associated with cancer TMN stage. Conclusions: The mtDNA levels in blood samples may represent a promising, non-invasive biomarker in breast cancer patients. Additional, large-scale validation studies are required to establish the potential use of mtDNA levels in the early diagnosis and monitoring of breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8075-8081
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• 2014

Background: The classical inflammatory biomarker, C-reactive protein (CRP), has been identified to be related to progression of esophageal cancer. Some research showed that elevated pretreatment serum CRP indicated a poor prognosis, but results have been inconsistent. Materials and Methods: We searched the Medline, Embase and the Cochrane Central Search Library for suitable studies and a meta-analysis of eleven (1,886 patients) was conducted to examine the relationship between elevated serum CRP level and overall survival (OS) in esophageal cancer cases. Moreover, correlation analyses were conducted to assess links between pretreatment serum CRP level and tumor node metastasis (TNM) stage as well as T, N, M grade, respectively. Results: The pooled analysis showed that elevated pretreatment serum CRP level was significantly associated with poorer overall survival (HR 2.09, 95%CI 1.52-2.87, p<0.01). Subgroup analyses were conducted by "country", "cut-off value", "treatment" and "number of patients", and no single factor could alter the result. Elevated pretreatment serum CRP was significantly correlated with more advanced TNM stage and T, N, M grade respectively. Conclusions: Elevated pretreatment serum CRP levels are associated with poorer prognosis in esophageal cancer patients, and could serve as a useful biomarker for outcome prediction.

• Asian Pacific Journal of Cancer Prevention
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• 제14권7호
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• pp.4215-4221
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• 2013

Purposes: Lung cancer is prevalent worldwide and improvements in timely and effective diagnosis are need. Pentraxin-3 as a novel serum marker for lung cancer (LC) has not been validated in large cohort studies. The aim of the study was to assess its clinical value in diagnosis and prognosis. Methods: We analyzed serum PTX-3 levels in a total of 1,605 patients with LC, benign lung diseases and healthy controls, as well as 493 non-lung cancer patients including 12 different types of cancers. Preoperative and postoperative data were further assessed in patients undergoing LC resection. The diagnostic performance of PTX-3 for LC and early-stage LC was assessed using receiver operating characteristics (ROC) by comparing with serum carcinoembryonic antigen (CEA), cytokeratin 19 fragments (CYFRA 21-1). Results: Levels of PTX-3 in serum were significantly higher in patients with LC than all controls. ROC curves showed the optimum diagnostic cutoff was 8.03ng/mL (AUC 0.823, [95%CI 0.789-0.856], sensitivity 72.8%, and specificity 77.3% in the test cohort; 0.802, [95%CI 0.762-0.843], sensitivity 69.7%, and specificity 76.4% in the validate cohort). Similar diagnostic performance of PTX-3 was observed for early-stage LC. PTX-3 decreased following surgical resection of LC and increased with tumor recurrence. Significantly elevated PTX-3 levels were also seen in patients with non-lung cancers. Conclusions: The present data revealed that PTX-3 was significantly increased in both tissue and serum samples in LC patients. PTX-3 is a valuable biomarker for LC and improved identification of patients with LC and early-stage LC from those with non-malignant lung diseases.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.1057-1060
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• 2013

Recent investigations have confirmed up-regulation of serum miR-21 and its diagnostic and prognostic value in several human malignancies. In this study, we examined serum miR-21 levels in epithelial ovarian cancer (EOC) patients, and explored its association with clinicopathological factors and prognosis. The results showed significantly higher serum miR-21 levels in EOC patients than in healthy controls. In addition, increased serum miR-21 expression was correlated with advanced FIGO stage, high tumor grade, and shortened overall survival. These findings indicate that serum miR-21 may serve as a novel diagnostic and prognostic marker, and be used as a therapeutic target for the treatment of EOC.

• KSBB Journal
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• 제26권4호
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• pp.352-356
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• 2011

The detection of biomarkers is an important issue for disease diagnosis. However, many systems are not suitable to detect the biomarker itself directly. For direct detection of biomarker proteins in human serum, a new affinity-capture method using aptamers combined with the mass spectrometry was suggested. Since signals from protein samples cannot be amplified, modified chromatin immunoprecipitation (ChIP) and subsequent cross-linking with formaldehyde between aptamers and target proteins were used not to lose the captured target proteins, which allowed us to perform a harsh washing step to remove the non-specifically bound proteins. As a model system, a thrombin aptamer was used as a bait and thrombin as a target protein. Using our modified ChIP and affinity-capture method, non-specific binding proteins on the beads decreased significantly, suggesting that our new method is efficient and can be applied to developing diagnosis systems for various biomarkers.

• 대한의용생체공학회:의공학회지
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• 제30권2호
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• pp.122-128
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• 2009

Cancer serum biomarkers have advanced our ability to more accurately predict tumor classification, prognostic/metastatic potential, and response potential to novel chemotherapies. Serum amyloid A (SAA) and Vascular endothelial growth factor (VEGF) have potential utility as a serum biomarker for lung cancer. Quantum dots, nanometer-sized crystals, have a high quantum yield, sensitivity, and pronounced photostability. The properties of quantum dots can be efficiently applied to the detection of serum biomarkers in immunoassays as fluorescent probe. We used quantum dots as fluorescent probes in immunoassays and attempted to detect serum amyloid A and vascular endothelial growth factor as serum biomarkers of lung cancer. This fluorescence immunoassay based on the properties of quantum dots is applicable to the detection of serum biomarkers for lung cancer. The fluorescence immunoassay with quantum dots should allow the efficient and specific detection of serum amyloid A (SAA) for the possible diagnosis of lung cancer.

• The Korean Journal of Physiology and Pharmacology
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• 제10권4호
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• pp.187-191
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• 2006

Serum ferritin levels are increased in subjects at-risk for or with acute lung injury (ALI), and there are observations to suggest that increases in serum ferritin levels may help predict the development of ALI in at-risk individuals. To deepen our understanding of increases of serum ferritin and their relationship to the development of ALI, we measured serum ferritin levels before and after intestinal ischemia/reperfusion (I/R) injury in rats, and found that serum ferritin levels increased significantly following I/R. Increases in serum and lavage ferritin levels paralleled increases in lung inflammation (lavage leukocyte numbers and tissue myeloperoxidase activities) and lung leak (lavage protein levels). In contrast, pre-treatment of rats with mepacrine (60 mg/kg, i.p.), a phospholipase $A_2$ inhibitor, attenuated not only I/R-induced serum and lavage ferritin increases, but also the development of ALI. These findings indicate that, besides of human subjects with ALI, serum ferritin levels increase early on also in an animal model of ALI. Therefore, serum and lavage ferritin can be a candidate for early biomarker of ALI.

• Clinical and Experimental Reproductive Medicine
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• 제45권2호
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• pp.94-99
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• 2018

Objective: Prompt diagnosis and management are essential for saving the adnexal organs from infarction in cases of ovarian torsion (OT). This study aimed to determine the diagnostic significance of signal peptide, complement C1r/C1s, Uegf, and Bmp1 (CUB), and epidermal growth factor-like domain-containing protein-1 (SCUBE-1) levels in cases of OT, an emergent ischemic condition, and the relationship of SCUBE-1 with oxidative stress parameters. Methods: This prospective study was conducted among 15 OT patients and 20 age- and gravidity-matched healthy women. SCUBE-1 serum concentrations were determined by using enzyme-linked immunosorbent assays. In addition, oxidative stress was evaluated by measuring the serum levels of advanced oxidation protein products (AOPP), ferric reducing ability of plasma (FRAP), and glutathione (GSH). Results: The SCUBE-1 titers were significantly higher in the patients with OT than in the controls (p=0.008). In addition, serum FRAP and GSH levels were significantly lower in the OT patients than in the controls (p<0.001 for both). Serum AOPP levels were higher in the OT patients, but this trend was not statistically significant (p>0.05). Furthermore, there were no correlations between SCUBE-1 levels and age, gravidity, parity, cyst size, and AOPP, FRAP, or GSH levels (p>0.05). Conclusion: We believe that SCUBE-1 may be a promising biomarker for the early diagnosis of OT.

• Asian Pacific Journal of Cancer Prevention
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• 제17권1호
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• pp.109-115
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• 2016

Background: P53 has been reported to be involved with tumorigenesis and has also been implicated as a significant biomarker in oral squamous cell carcinoma(OSCC). However, the diagnostic value of p53 antibodies remains controversial; hence, we comprehensively and quantitatively assessed the potential in the present systematic review. Materials and Methods: A comprehensive search was performed using PubMed and Embase, up to October 31, 2014, without language restriction. Studies were assessed for quality using QUADAS (quality assessment of studies of diagnostic accuracy). The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were pooled separately and compared with overall accuracy measures using diagnostic odds ratios (DORs) and symmetric summary receiver operating characteristic (SROC) curves. Results: Of 150 studies initially identified, 7 eligible regarding serum p53 antibodies met the inclusion criteria. Some 85.7% (6/7) were of relatively high quality (QUADAS $score{\geq}7$). The summary estimates for quantitative analysis of serum p53 antibody in the diagnosis of squamous cell carcinoma were: PLR 2.06 [95% confidence interval (CI) : 1.35-3.15], NLR 0.85 (95%CI: 0.80-0.90) and DOR 2.47 (95%CI: 1.49-4.12). Conclusions: This meta-analysis suggests that the use of s-p53-antibodies has potential diagnostic value with relatively high sensitivity and specificity for OSCC particularly with serum specimens for discrimination of OSCCs from healthy controls. However, its discrimination power is not perfect because of low sensitivity.