The isolation and identification of apolipoprotein C-I in hormone-refractory prostate cancer using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry

Abstract

Androgens play a central role in prostate cancer pathogenesis, and hence most of the patients respond to androgen deprivation therapies. However, patients tend to relapse with aggressive prostate cancer, which has been termed as hormone refractory. To identify the proteins that mediate progression to the hormone-refractory state, we used protein-chip technology for mass profiling of patients' sera. This study included 16 patients with metastatic hormone-refractory prostate cancer who were initially treated with androgen deprivation therapy. Serum samples were collected from each patient at five time points: point A, pre-treatment; point B, at the nadir of the prostatespecific antigen (PSA) level; point C, PSA failure; point D, the early hormone-refractory phase; and point E, the late hormone-refractory phase. Using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, we performed protein mass profiling of the patients' sera and identified a 6 640-Da peak that increased with disease progression. Target proteins were partially purified, and by amino acid sequencing the peak was identified as a fragment of apolipoprotein C-I (ApoC-I). Serum ApoC-I protein levels increased with disease progression. On immunohistochemical analysis, the ApoC-I protein was found localized to the cytoplasm of the hormone-refractory cancer cells. In this study, we showed an increase in serum ApoC-I protein levels in prostate cancer patients during their progression to the hormone-refractory state, which suggests that ApoC-I protein is related to progression of prostate cancer. However, as the exact role of ApoC-I in prostate cancer pathogenesis is unclear, further research is required.

The use of matrix coating assisted by an electric field (MCAEF) to enhance mass spectrometric imaging of human prostate cancer biomarkers

“…, in our study, high levels of both apolipoprotein A‐I and apolipoprotein A‐II were found in the cancerous cell region in prostate cancer, in contrast with the previous study . Apolipoprotein C‐I has also been shown to be a potential biomarker for prostate cancer with high expression levels in serum based on surface‐enhanced LDI‐TOF MS and immunohistochemical analysis, which is consistent with our MALDI‐MSI study (Fig. B), where the peptide at m / z 6633.1 (apolipoprotein C‐I) was mainly distributed in the cancerous region of the tissue.…”

Identification of Apolipoprotein C-I as a Potential Wilms’ Tumor Marker after Excluding Inflammatory Factors

“…It is secreted by the liver and is mainly distributed on the surface of very low density lipoprotein (VLDL), chylomicrons (CM) and high density lipoprotein (HDL) [ 14 ]. At present, APO C-I is a potential serum marker for colorectal cancer [ 15 ], prostate cancer [ 16 ], breast cancer [ 17 ], lung cancer [ 18 ], papillary thyroid carcinoma [ 19 ], malignant pleural mesothelioma [ 20 ], and liver fibrosis [ 21 ]. It has also been suggested as a potential serum marker for gastric cancer [ 22 ], which may be related to the regulation of its gene expression [ 23 ].…”

Multiplexed MRM-based quantitation of candidate cancer biomarker proteins in undepleted and non-enriched human plasma

“…1). According to Polanski's compilation [17] and other recent references [21][22][23][24][25][26][27][28][29][30][31][32][33], there are 14 proteins in the panel that have been linked to multiple types of cancer. For instance, serum paraoxonase/arylesterase 1 has been observed to be downregulated in patients with gastric [34] and pancreatic [35] cancers.…”