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<sec>
<title>Objectives</title>
<p>This study was designed to analyze biomarker-related publications and patent trends which biobanks could consider in planning biosample collections for biomarker research.</p></sec>
<sec>
<title>Methods</title>
<p>Publications and patents containing the term “biomarker” in the title published between 1998 to 2017 were retrieved using Scopus database and Google Patents search engine.</p></sec>
<sec>
<title>Results</title>
<p>Over the last 20 years there has been a steady increase in biomarker-related publications and patents; however this has slowed for patents over the last few years. Publications in 2017 that contained blood, serum, and plasma search terms in the abstract accounted for 50%, and serum as a search term in the title and abstract was more numerous than those containing blood, plasma, tissue, or urine. Blood-related patents were the most common patent in the last 10 years, and accounted for 110 patents in 2017. Biomarker-related publications since 2010 containing RNA and protein search terms in the title and abstract, were more numerous than those containing DNA and metabolite search terms. More than 27% of biomarker-related publications in 2017 and 21% of biomarker-related patents were associated with cancer.</p></sec>
<sec>
<title>Conclusion</title>
<p>The results of this study will help biobanks establish a biosample collection strategy for clinical application.</p></sec>
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Objectives
Progastrin-releasing peptide (proGRP) is a promising biomarker for small cell lung cancer. However, not much is known about how sample processing and storage conditions affect the stability of proGRP. Here, we examined the effects of repeated freeze–thaw cycles on the stability of proGRP in plasma and serum. Methods
Concentrations of proGRP were measured in plasma and serum samples exposed to two, three, or four freeze–thaw cycles and these were compared with values of corresponding samples exposed to one cycle (baseline). We also performed the area under the receiver-operating-characteristic curve (AUC) analysis to determine whether the differences of proGRP concentrations between each paired plasma and serum sample (ΔproGRP) can be used for identifying the samples that have been exposed to multiple freeze–thaw cycles. Results
Concentrations of proGRP gradually decreased in both plasma and serum samples with increasing numbers of freeze–thaw cycles. Reduction rates of proGRP concentrations were greater in serum than in plasma samples and serum proGRP levels declined with statistical significance (<i>p</i> < 0.001) up to 10.1% after four freeze–thaw cycles. The ΔproGRP measurement showed fair accuracy (AUC = 0.741) for identifying samples that had been through four freeze–thaw cycles. The sensitivity was 82.8% and specificity was 62.1% at an optimal cut-off point of > 4.9. Conclusion
Our study shows that the stability of circulating proGRP is affected in both plasma and serum samples by repeated freezing and thawing. We also show that ΔproGRP could be used for identifying paired plasma and serum samples subjected to multiple freeze–thaw cycles.
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Objectives
The delayed separation of whole blood can influence the concentrations of circulating blood components, including metabolites and cytokines. The aim of this study was to determine whether clinical-biochemistry analytes can be used to assess the delayed separation of whole blood. Methods
We investigated the plasma and serum concentrations of five clinical-biochemistry analytes and free hemoglobin when the centrifugation of whole blood stored at 4°C or room temperature was delayed for 4 hours, 6 hours, 24 hours, or 48 hours, and compared the values with those of matched samples that had been centrifuged within 2 hours after whole-blood collection. Results
The inorganic phosphorus (IP) levels in the plasma and serum samples were elevated ≥ 1.5-fold when whole-blood centrifugation was delayed at room temperature for 48 hours. Furthermore, the IP levels in the plasma samples showed excellent assessment accuracy [area under the receiver-operating-characteristic curve (AUC) > 0.9] after a 48-hour delay in whole-blood separation, and high sensitivity (100%) and specificity (95%) at an optimal cutoff point. The IP levels in the serum samples also exhibited good assessment accuracy (AUC > 0.8), and high sensitivity (81%) and specificity (100%). The potassium (K<sup>+</sup>) levels were elevated 1.4-fold in the serum samples following a 48-hour delay in whole-blood separation. The K<sup>+</sup> levels showed excellent assessment accuracy (AUC > 0.9) following a 48-hour delay in whole-blood separation, and high sensitivity (95%) and specificity (91%) at an optimal cutoff point. Conclusion
Our study showed that the IP and K<sup>+</sup> levels in the plasma or serum samples could be considered as putative indicators to determine whether whole-blood separation had been delayed for extended periods.
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Objectives
The stability of circulating proteins can be affected by repeated freezing and thawing. The aim of our study was to identify the effect of repeated freezing and thawing on the plasma and serum concentrations of eight proteins [interferon-γ, interleukin (IL)-8, IL-15, IL-17A, matrix metalloproteinase (MMP)-7, tumor necrosis factor-α, vascular endothelial growth factor (VEGF), and VEGF receptor 2 (VEGF-R2)]. Methods
We assessed the concentration changes of these proteins in 30 plasma and serum samples subjected to three, four, or five freeze–thaw cycles, and compared these with the concentration changes in the samples that were subjected to two freeze–thaw cycles before analysis. Results
Repeated freezing and thawing by up to five cycles did not modify the plasma and serum concentrations of interferon-γ, IL-8, and VEGF-R2, while levels of MMP-7, tumor necrosis factor-α, and VEGF were significantly changed in both plasma and serum samples. Moreover, MMP-7 and VEGF concentrations tended to increase with freeze–thaw cycles. They were more elevated in plasma samples (up to about 15%) than in serum samples (up to about 7%), suggesting that serum is the preferred sample type for the analysis of circulating proteins. Conclusion
This is the first report on the effect of repeated freezing and thawing on plasma concentrations of MMP-7 and VEGF-R2. Our findings propose that researchers should consider the number of freeze–thaw cycles to select plasma or serum samples, depending on the type of analyte.
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Objectives
Epstein Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) are a useful biological resource, however, genomic variations can happen during the generation and immortalization processes of LCLs. The purpose of this study was to identify genomic variations in LCL DNA compared with matched blood DNA using short tandem repeats (STRs) analysis. Methods
We analyzed 15 STRs with blood DNA and their matched LCL DNA samples from 6645 unrelated healthy individuals. Results
Mutations (such as repeat variations and triallelic patterns) of 15 STR loci were detected in 612 LCL DNAs (9.2% of total) without mutations in their matched blood DNA. The repeat variations of 15 STRs were detected in 526 LCL DNAs (mutation rate = 0.0792) and triallelic patterns were identified in 123 (mutation rate = 0.0185). Among 15 STRs, the most common repeat variations (<i>n</i> = 214, mutation rate = 0.0322) and triallelic patterns (<i>n</i> = 17, mutation rate = 0.0026) were found at FGA locus. Conclusion
Our study shows that mutations in STRs can occur during generation and immortalization of LCLs.
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Personalized medicine is emerging as a main paradigm for risk prediction, pre-diagnosis, and effective prevention and treatment of disease. A large number of human biospecimens and their clinical data are essential resources for the success of personalized medicine as well as other biomedical research. The National Biobank of Korea (NBK) has collected well-annotated and high quality human biospecimens, and distributes them to the Korean biomedical scientists, through the Korea Biobank Project (KBP). The ultimate goal of NBK activities is to promote biomedical research and public health. As of December- 2011, the NBK has collected various human biospecimens from 525,416 participants including 325,952 Korean populations and 199,464 patients. The purpose of this paper is to introduce the KBP and quality control programs for collection of human biospecimens with high quality of NBK.
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