Proteome Analysis Distinguishes Gallbladder Cancer from Gallstone Disease in Patients of African Ancestry

Abstract

Introduction: Gallbladder cancer (GBC) has a poor 5-year survival rate prognosis suggesting the need for more effective treatment strategies. Gallstone disease has been identified as a precursor for GBC. Gallbladder tissue proteome analysis may prove beneficial in identifying key players of GBC progression. This study aimed to identify dysregulated proteins implicated in GBC progression from gallstone disease. Methods: Tissue samples were obtained from 29 GBC and 15 gallstones patients (M190555). Protein extraction was performed on tissues. Thereafter, liquid chromatography-mass spectrometry was performed using a Dionex 3000 RSLC system coupled to an AB Sciex 6600 TripleTOF mass spectrometer. A spectral library was built in Spectronaut v14 (Biognosys Schlieren, Switzerland) using the Pulsar search algorithm. Across the complete study sample set, 50,201 peptides were matched to 5,139 protein groups. Results: We observed 247 dysregulated proteins (131 upregulated and 116 downregulated) in the GBC patient group. A q-value <0.01 and fold change (FC) of >3.2 was applied, as per power analysis (0.9 power value selected) performed using the designSampleSize function within MSstats. The top upregulated proteins included MYG (FC = 7.39), SPB5 (FC = 6.21), and OLFM4 (FC = 5.57). The top downregulated proteins include RNAS2 (FC = -4.72), TRYB2 (FC = -4.38), and CNTN1 (FC = -3.90). Pathway analysis showed that the dysregulated proteins were enriched in pathways involved in metabolism and muscle contraction. Conclusion: This study has identified proteins that could distinguish GBC from gallstone disease. Further studies are ongoing to verify the dysregulation and spatial expression of these proteins.