Institute of Diagnostics, Department of Clinical Chemistry, PL 5000, FI-90014, University of Oulu, Oulu.
Ann Clin Biochem. 2011 Sep;48(Pt 5):447-51. doi: 10.1258/acb.2011.011040. Epub 2011 Jul 6.
Aminoterminal propeptide of type I procollagen (PINP) reflects bone formation. Two different antigens exist in human serum: intact PINP and a monomeric form. The intact PINP assay measures trimeric form and the total assay measures both forms. The structure and origin of the monomeric form is still unclear.
Automated intact and total PINP assays were compared in breast cancer patients with (n = 60) or without bone metastases (n = 226). In addition, cross-linked carboxyterminal telopeptide of type I collagen (ICTP) was measured from the same patients and compared with the concentration of PINP monomer (difference between intact and total PINP). Monomeric PINP was purified from human ascitic fluid and characterized by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).
The correlations were good (r > 0.948) between intact PINP and total P1NP in all patient groups. The correlation between the monomeric form and ICTP was lower in patients without bone metastases (r = 0.507) than in patients with bone metastases (r = 0.894). This indicates that the monomeric form reflects the degradation of type I collagen because bone metastases are osteolytic in nature. After several steps in the purification of the monomer form there was a single peak. Only the single band was visible in the SDS-PAGE gel. The alpha1-chain of intact PINP consists of 161 amino acids with a molecular weight of 14224.02. The purified monomer peptide in MALDI-TOF MS was smaller, 10576.41, and most likely cleaved after the arginine residue (amino acid number 120) with a trypsin-like protease.
Intact and total PINP assays give similar results in many conditions, but there are differences, for example in breast carcinoma, which should be recognized.
I 型前胶原氨基端前肽（PINP）反映了骨形成。人血清中存在两种不同的抗原：完整的 PINP 和单体形式。完整的 PINP 测定法测定三聚体形式，总测定法测定两种形式。单体形式的结构和来源尚不清楚。
比较了 60 例乳腺癌伴骨转移患者（n=60）和 226 例无骨转移患者（n=226）的全自动完整和总 PINP 测定值。此外，还从同一患者中测量了 I 型胶原交联羧基末端肽（ICTP）并与 PINP 单体浓度（完整和总 PINP 之间的差异）进行比较。从人腹水纯化单体 PINP，并用十二烷基硫酸钠聚丙烯酰胺凝胶电泳（SDS-PAGE）和基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF MS）进行鉴定。
所有患者组中，完整 PINP 与总 PINP 的相关性均良好（r>0.948）。无骨转移患者（r=0.507）单体形式与 ICTP 的相关性低于骨转移患者（r=0.894），表明单体形式反映了 I 型胶原的降解，因为骨转移本质上是溶骨性的。单体形式经过几个纯化步骤后，出现了一个单一的峰。SDS-PAGE 凝胶中仅可见单一条带。完整 PINP 的α1 链由 161 个氨基酸组成，分子量为 14224.02。MALDI-TOF MS 中纯化的单体肽较小，为 10576.41，很可能在胰蛋白酶样蛋白酶作用下，在精氨酸残基（120 号氨基酸）后被切割。
在许多情况下，完整和总 PINP 测定法的结果相似，但也存在差异，例如在乳腺癌中，应加以识别。
