Screening for specific biomarkers in the serum of postmenopausal osteoporosis patients using proteomic fingerprint techniques

Abstract

Abstract. The aim of this study was to detect serum protein biomarkers and establish a diagnostic model for postmenopausal osteoporosis (PMOP) adopting matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with weak cationic exchange (WCX) magnetic beads, and to study the clinical significance of the model in the early diagnosis of PMOP. Serum samples from 45 patients with PMOP, 30 patients with osteopenia and 40 healthy controls were prepared using WCX magnetic beads, and were then analyzed using a PBSⅡ-C mass spectrometer reader. The protein spectra of the serum samples were normalized using the Ciphergen Proteinchip software. The peak labeling was performed using the Biomarker Wizard software. The specific protein biomarkers were screened using the Biomarker Pattern software to construct a diagnostic model for PMOP. A total of 138 discriminative mass-to-charge (m/z) ratios were found to be associated with PMOP. Of these, the m/z peaks at 3167.4, 4071.1, 7771.7 and 8140.5 were used to construct a diagnostic model in a training set. In a test set, the sensitivity and specificity of the model were 91.11 and 92.86%, respectively. Potential protein biomarkers for PMOP were detected in patient serum using MALDI-TOF MS combined with WCX magnetic beads. This model of multiple biomarkers provided a powerful and reliable diagnostic method for PMOP diagnosis with high sensitivity and specificity. IntroductionPostmenopausal osteoporosis (PMOP) is a bone disease resulting from low estrogen levels, causing reduced bone mass and bone microstructure degeneration and increased fragility of bones and fractures (1). It is a serious, frequently-occurring disease in older women. As estimated by the epidemiological survey in 2009, the incidence of the disease was 19.9 and 24% in women aged >40 and >60 years, respectively. Therefore, PMOP, which has become a serious public health concern, receives much attention (2).With the advances in proteomics research, proteomics techniques show a notably high sensitivity and specificity in screening for biomarkers of various diseases. Currently, an increasing number of studies employs such techniques to investigate the disease-associated whole and differential proteins, in order to explore the composition and dynamic changes of the disease proteins at the whole level to gain a better understanding of the various physiological and pathological processes in individuals, as well as to search for highly effective diagnostic markers of various diseases. Matrix-assisted laser desorption/ionization time-of-light mass spectrometry (MALDI-TOF MS) is a recently emerged proteomics method, with the potential to detect various clinical samples, such as serum, urine, pleural effusion, ascites and a number of secretions (3,4). Therefore, MS technique is a milestone in clinical detection. The present study employed MALDI-TOF MS combined with weak cationic exchange (WCX) magnetic beads to analyze the normal bone mass in postmenopausal women and the serum protein ...

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