Proteomic-based analysis for identification of potential serum biomarkers in gallbladder cancer

Abstract

Abstract. Gallbladder cancer is the most common malignant tumor of the biliary tract. Early diagnosis of gallbladder cancer is difficult because of the latent onset and lack of good biomarkers. To identify new biomarkers that improve the early diagnosis and/or serve as possible therapeutic targets in gallbladder cancer is essential. In the present study, serum proteins were separated by two-dimensional gel electrophoresis (2-DE) in 3 patients with gallbladder cancer and 3 healthy volunteers. The differentially expressed spots were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Western blotting and immunohistochemistry were performed to verify the expression of certain candidate proteins. Protein expression and clinical correlation was evaluated. We found that 64 protein spots were significantly changed in gallbladder cancer. Twenty-four proteins including S100A10, haptoglobin, cystatin-B, profilin-1 and superoxide dismutase were successfully identified. Among these proteins, S100A10 and haptoglobin were validated using Western blotting. Immunohistochemically, the expression of S100A10 and haptoglobin proteins was found to be higher in gallbladder cancer tissues compared to that in gallbladder adenoma, liver cholangiocarcinoma and cholecystitis tissue. Patients with high expression of S100A10 and haptoglobin were linked to late stage disease and poor clinical prognosis. Our data suggest that combined comparative proteomic analysis by 2-DE and MALDI-TOF-MS is an effective method for identifying differentially expressed proteins in serum samples. These proteomic approaches could be used for identifying new serum biomarkers in gallbladder cancer. S100A10, haptoglobin and other identified proteins may be potential molecular targets for early gallbladder cancer diagnostics and therapeutic applications.

S100A10 protein expression is associated with oxaliplatin sensitivity in human colorectal cancer cells

“…We have also demonstrated the presence of S100A10 in cell culture supernatant (Figure 6), suggesting that S100A10 undergoes extracellular secretion. In addition, recently, S100A10 was detected in human serum and the list of plasma protein [49,50], thereby allowing blood level monitoring of S100A10 for further clinical validation as a biomarker for the L-OHP sensitivity.…”

S100A10 and Cancer Hallmarks: Structure, Functions, and its Emerging Role in Ovarian Cancer

“…However, increased levels of S100A10 are present in all anaplastic thyroid carcinomas, which is the most aggressive form of thyroid malignancy, suggesting that S100A10 plays a role in the progression of thyroid carcinomas [76]. Tan et al reported that high cytoplasmic S100A10 expression in advanced stage gallbladder carcinoma is associated with poor prognosis [77]. Overexpression of S100A10 is also associated with poor prognosis in lung carcinoma [78,79] and pancreatic cancer [80].…”

Identification of prosaposin and transgelin as potential biomarkers for gallbladder cancer using quantitative proteomics

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