Breast cancer is the most common malignancy in women worldwide. But to date, there is no good serum protein marker for breast cancer diagnosis and prognosis. We conducted this study to screen and identify specific protein markers of breast cancer.
Mass spectrometry was applied to screen and identify differential serum protein profiles between 63 breast cancer patients and 40 healthy controls. Immunohistochemistry (IHC) and western blot analysis were used as verification experiments. Biological functions of candidate protein marker were studied in vitro.
Two amino acid fragments with sizes of 3.9kDa and 5.6kDa, respectively, were detected as candidate markers. A combined diagnostic model composed of these two fragments was built, with a sensitivity of 82.3% and a specificity of 95.3%. The 5.6kDa fragment, which was up regulated in breast cancer, was an important segment of lamina-associated polypeptide 2 alpha (LAP2α). IHC and western blot experiments confirmed over expression of LAP2α in breast cancer tissues. An inhibition plasmid vector of LAP2α-small hairpin RNA (shRNA) was constructed and transfected into MCF-7 cells. CCK-8 experiments on transfected cells showed that inhibition of LAP2αcould not influent cell proliferation. Transwell and matrigel-transwell assays indicated that inhibition of LAP2α could significantly reduce cell migration and invasion abilities.
We built a diagnostic model for early detection of breast cancer with a satisfactory accuracy. LAP2αwas identified as a candidate serum protein marker, which was overexpressed in breast cancer. Inhibition of LAP2αcould suppress MCF-7 cell aggressiveness. Our study indicated that LAP2αcould be a potential serum biomarker and therapeutic target of breast cancer.
Clinical trial indentification
Legal entity responsible for the study
The Second Affiliated Hospital, Zhejiang University School of Medicine, China
Zhejiang Provincial Natural Science Foundation of China
All authors have declared no conflicts of interest.