OBJECTIVETo screen serum biomarker candidates in prostate cancer with bone metastasis by two-dimensional gel electrophoresis (2-DGE) and mass spectrometry.

METHODSSerum samples were obtained from 5 prostate cancer patients with bone metastasis, and another 5 without it. After depletion of the most abundant protein albumin from the serum, the samples were separated by 2-DGE and analyzed with the ImageMaster 2D Platinum software. The differentially expressed protein spots in the serum of those with bone metastases were identified by peptide-fingerprinting with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS).

RESULTSCompared with the serum samples from those without bone metastasis, 10 protein spot-features were found to be significantly increased and 5 significantly decreased, and the 3 identified proteins, Zn-alpha2-glycoprotein (ZAG), haptoglobin and apolipoprotein C-III, were all increased in the bone-metastasis group.

CONCLUSIONThe combination of 2-DGE and mass spectrometry is an ideal platform and an effective means for the differential proteomic analysis of human sera. The identified proteins involved in the formation and progression of prostate cancer bone metastasis might be applied as biomarkers for bone metastasis from prostate cancer.

Aged ; Aged, 80 and over ; Bone Neoplasms ; blood ; secondary ; Case-Control Studies ; Electrophoresis, Gel, Two-Dimensional ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Prostatic Neoplasms ; blood ; pathology ; Proteome ; analysis ; Proteomics

Breast cancer is the second leading cause of cancer death in women today. Once breast cancer metastasizes to bone, mortality increases. Thus, there is an urgent need to identify patients with high risk of bone metastasis, and to find predictive factors for the occurrence of bone metastasis at an earlier stage of breast cancer. Three hundred and sixty patients with pathologically proved breast cancer visiting the Department of Nuclear Medicine for whole body bone scan from January 2006 and January 2009 were investigated in this study. Clinicopathological information was obtained, which consisted of age, menopausal status, clinical staging, lymph node stage, histological grade, the expression of estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2). Correlation between bone metastasis and the associated factors was tested by using the Chi-square test. A Cox multivariate analysis was used to assess the factors which independently contributed to survival after bone metastasis in breast cancer patients. Survival curves were drawn for metastasis-free interval and the independent factors which contributed to survival, using the Kaplan-Meier method. Twenty-four patients were excluded from subsequent analysis. Three hundred and thirty-six enrolled patients ranged in age from 22 to 77 years (mean, 47.8 years). ER/PR status [ER(+) vs. ER(-), χ (2)=4.328, P=0.037; ER(+)PR(+) vs. ER(+)PR(-), χ (2)=4.425, P=0.035] and histological grade (χ (2)=7.131, P=0.028) were significantly associated with bone metastasis. ER status (x (2)=8.315, P=0.004) and metastasis-free interval (χ (2)=6.863, P=0.009) were independent prognostic factors for survival in breast cancer patients with bone metastasis. Our study suggested that ER/PR status and histological grade are risk factors for the development of bone metastasis in breast cancer patients. However, ER status and metastasis-free interval are independent prognostic factors for survival in breast cancer patients with bone metastasis. Breast cancer bone metastasis has its unique characteristics, which is helpful to choose the appropriate treatment for breast cancer patients with bone metastasis.
Adult ; Aged ; Biomarkers, Tumor ; metabolism ; Bone Neoplasms ; metabolism ; mortality ; secondary ; Breast Neoplasms ; metabolism ; mortality ; China ; epidemiology ; Female ; Humans ; Middle Aged ; Molecular Diagnostic Techniques ; statistics & numerical data ; Prevalence ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Risk Factors ; Survival Rate ; Young Adult