Frederiksen C B, Lomholt A F, Lottenburger T, Davis G J, Dowell B L, Blankenstein M A, Christensen I J, Brunner N, Nielsen H J
Department of Surgical Gastroenterology, Hvidovre University Hospital, Hvidovre - Denmark.
Int J Biol Markers. 2008 Jan-Mar;23(1):42-7. doi: 10.1177/172460080802300107.
Tissue inhibitor of metalloproteinases-1 (TIMP-1) measurements in plasma may be useful for the early detection and prognosis of colorectal cancer (CRC). Data on analytical performance and normal intra- and interindividual biological variation are required in order to interpret the utility of TIMP-1 in CRC. The aim of this study was to establish the biological and analytical variation of plasma TIMP-1 in volunteers.
Three separate studies were undertaken. 1: Plasma was collected from 23 volunteers 6 times within a 3-week period, first in September 2004 (round [R] 1), then repeated in May 2005 (R2) and May 2006 (R3) in the same group of individuals. TIMP-1 levels were determined by the MAC15 ELISA assay and with the Abbott ARCHITECT i2000 Immunoanalyzer. 2: Circadian variation was evaluated in plasma collected 7 times within a 24-hour period (n=16). 3: Effects of physical exercise were evaluated in plasma collected before and after bicycling (n=14). In studies 2 and 3 TIMP-1 levels were determined with the MAC15 ELISA assay only.
A significant correlation between TIMP-1 MAC15 and ARCHITECT i2000 was shown (rs=0.78, p<0.002), with consistently higher levels being detected by the ARCHITECT i2000. Median levels of TIMP-1 (ARCHITECT) at 8 a.m. in each round were 74.9 ng/mL (range 65.7-89.9) (R1), 87.3 ng/mL (range 72.7-127.9) (R2), and 81.9 ng/mL (range 66.8-113.6) (R3). The within-subject variation was 10.7%, the variation between rounds was 7.4%, and the intraclass correlation was 46.2%. Comparison between the 3 rounds and time of collection showed that TIMP-1 values decreased by 11% after storage for more than 16 months (p=0.0002). A systematic circadian variation in plasma TIMP-1 levels was not observed (p=0.17). No significant variation of plasma TIMP-1 was found in relation to physical exercise (p=0.92 [global test]).
Levels of plasma TIMP-1 in volunteers show limited circadian, day-to-day, week-to-week and season-to-season variation. In addition, physical exercise has no impact on plasma TIMP-1 levels. Possible storage-dependent decreases in plasma TIMP-1 levels warrant further investigation.
血浆中金属蛋白酶组织抑制剂-1（TIMP-1）的检测可能有助于结直肠癌（CRC）的早期诊断和预后评估。为了解TIMP-1在CRC中的应用价值，需要有关分析性能以及个体内和个体间正常生物学变异的数据。本研究的目的是确定志愿者血浆中TIMP-1的生物学和分析变异。
进行了三项独立研究。1：在3周内从23名志愿者身上采集6次血浆，首次采集于2004年9月（第1轮[R]），然后于2005年5月（R2）和2006年5月（R3）在同一组个体中重复采集。TIMP-1水平通过MAC15 ELISA检测法和雅培ARCHITECT i2000免疫分析仪测定。2：在24小时内采集7次血浆（n = 16），评估昼夜变化。3：在骑自行车前后采集血浆（n = 14），评估体育锻炼的影响。在研究2和3中，仅通过MAC15 ELISA检测法测定TIMP-1水平。
TIMP-1 MAC15与ARCHITECT i2000之间显示出显著相关性（rs = 0.78，p < 0.002），ARCHITECT i2000检测到的水平始终较高。每一轮上午8点时TIMP-1（ARCHITECT）的中位数水平分别为74.9 ng/mL（范围65.7 - 89.9）（R1）、87.3 ng/mL（范围72.7 - 127.9）（R2）和81.9 ng/mL（范围66.8 - 113.6）（R3）。受试者内变异为10.7%，轮次间变异为7.4%，组内相关系数为46.2%。三轮检测结果与采集时间的比较表明，储存超过16个月后TIMP-1值下降了11%（p = 0.0002）。未观察到血浆TIMP-1水平有系统性的昼夜变化（p = 0.17）。未发现血浆TIMP-1水平与体育锻炼有显著相关性（p = 0.92[整体检验]）。
志愿者血浆中TIMP-1水平在昼夜、每日、每周和季节之间的变化有限。此外，体育锻炼对血浆TIMP-1水平没有影响。血浆TIMP-1水平可能存在的储存依赖性下降值得进一步研究。
