Abstract
BackgroundPancreatic cancer is a malignancy with a very poor prognosis. The emergence of liquid biopsy is expected to achieve accurate early diagnosis through detection of tumor-derived secreted proteins in the blood. Early diagnosis and treatment of pancreatic cancer could help to improve prognosis.MethodsThe pretreatment approach of samples can have a major effect on downstream analysis. In this study, we used a pair of homologous pancreatic cancer cell supernatants with different capacities for invasion and metastasis to examine secreted proteins in the conditioned media without the removal of fetal bovine serum, namely through size exclusion chromatography combined with high-abundance protein affinity chromatography to enrich low-concentration protein, followed by mass spectrometry using triple dimethyl labeling. Identification of proteins was performed using an online public database and western blot.ResultsMass spectrometry data revealed 77 proteins with quantitative properties, of which 12 proteins had over a 1.5-fold difference (in the supernatant of the highly invasive pancreatic cancer cell line PC-1.0, the expression of 8 proteins were increased and the expression of 4 proteins were decreased). Bioinformatics analysis results showed that CCT8, CTSL, SAA1, IGF2 are secreted via the exosome pathway. According to the literature, with the exception of CCT8, the other three proteins can be detected in blood samples of pancreatic cancer patients, and they can be used as prognostic markers. Western blot results were used to validate consistency with MS results.ConclusionThis study found that CCT8 can be used as a liquid biopsy marker to assess the prognosis of pancreatic cancer patients.
Highlights
Pancreatic cancer is a malignancy with a very poor prognosis
The results showed that the approximate distribution of proteins in the supernatant of pancreatic cancer cells: high molecular weight proteins were abundant, and there were fewer low molecular weight proteins
Using functional annotation clustering analysis in the software, we found that the primary cluster was exosome signaling, which included four proteins (CTSL, chaperonin-containing T-complex protein 8 (CCT8), insulin like growth factor 2 (IGF2) and serum amyloid A1 (SAA1))
Summary
Pancreatic cancer is a malignancy with a very poor prognosis. Diagnosis and treatment of pancreatic cancer could help to improve prognosis. Pancreatic cancer ranks fourth in cancer mortality in the United States. In 2019, 56,770 new cases of pancreatic cancer are expected in the United States. Surgical treatment is an option in only 15–20% of pancreatic cancer patients, and the overall 5-year survival rate is less than 5% [1, 2]. Diagnosis and appropriate treatment can significantly improve the prognosis of pancreatic cancer. With the advancement of experimental techniques, the number of molecular and chemical detection methods for pancreatic cancer has increased, and these methods have played an important role in the early diagnosis of pancreatic cancer [3]
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