Abstract
Breast cancer accounted for 15 per cent of total cancer deaths in female patients in 2010. Although significant progress has been made in treating early-stage breast cancer patients, there is still no effective therapy targeting late-stage metastatic breast cancers except for the conventional chemotherapy interventions. Until effective therapy for later-stage cancers emerges, the identification of biomarkers for the early detection of tumour metastasis continues to hold the key to successful management of breast cancer therapy. Our study concentrated on the low molecular weight (LMW) region of the serum protein and the information it contains for identifying biomarkers that could reflect the ongoing physiological state of all tissues. Owing to technical difficulties in harvesting LMW species, studying these proteins/peptides has been challenging until now. In our study, we have recently developed nanoporous chip-based technologies to separate small proteins/peptides from the large proteins in serum. We used nanoporous silica chips, with a highly periodic nanostructure and uniform pore size distribution, to isolate LMW proteins and peptides from the serum of nude mice with MDA-MB-231 human breast cancer lung metastasis. By matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and biostatistical analysis, we were able to identify protein signatures unique to different stages of cancer development. The approach and results reported in this study possess a significant potential for the discovery of proteomic biomarkers that may significantly enhance personalized medicine targeted at metastatic breast cancer.
Highlights
Breast cancer is the most frequently occurring malignancy and the second most frequent cause of cancer death in women in the USA and other Western countries [1]
We have developed nanoporous silica chips to capture low molecular weight (LMW) serum peptides and proteins [21,22,23,24,25,26]
With the specified molar ratio (1 : 0.006) of silicate to F-127 copolymer designed in this study, the final product yielded a three-dimensional honeycomblike nanostructure hexagonally arranged on the substrate, as depicted in its scanning transmission electron microscopy (STEM) plane view at low magnification and its Transmission electron microscopy (TEM) plane view at high magnification
Summary
Breast cancer is the most frequently occurring malignancy and the second most frequent cause of cancer death in women in the USA and other Western countries [1]. We used nanoporous silica chips to isolate LMW proteins and peptides from the serum of MDA-MB-231 lung metastatic cancer mice. To constitute a mouse model of breast cancer lung metastasis (BCLM), 3 × 105 MDA-MB-231/luciferase cells were washed and suspended in phosphate buffer solution (PBS), and subsequently injected into the lateral tail vein in a volume of 100 ml. MO, USA) in deionized water was prepared and vortex-mixed This pretreatment solution was added to the thawed serum samples in a 1 : 9 ratio to obtain final concentrations of ACN and TFA of 5 and 0.01 per cent, respectively. The t-value and corresponding p-value were calculated using MARKERVIEW between BCLM and the control groups
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