Proteomic Analysis identifies dysregulated proteins and associated molecular pathways in a cohort of South African Gallbladder cancer patients

ABSTRACT: Gallbladder cancer (GBC) is a lethal cancer with a poor prognosis. The lack of specific and sensitive biomarkers results in delayed diagnosis with most patients presenting at late stages of the disease. Furthermore, there is little known about the molecular mechanisms associated with GBC, especially in patients of African ancestry. This study aimed to determine dysregulated proteins in South African GBC patients to identify potential mechanisms of the disease progression and plausible biomarkers. Following ethics approval, tissues (27 GBC, 13 Gall stone disease, and 5 Normal tissues) and blood plasma (53 GBC and 73 Benign biliary pathology) were obtained from consenting patients. Protein extraction was performed on all tissues and liquid chromatography-mass spectrometry was used for proteomic profiling. A project-specific spectral library was built using the Pulsar search algorithm. Principal component and Spearman’s rank correlation analyses were performed using PAST (V4.07b). Pathway and Network analyses were conducted using REACTOME v3.7 and stringAPP (v1.7.0), respectively. Levels of the liver function tests such as total bilirubin, direct bilirubin, ALP, GGT, and AST were significantly elevated (p<0.05) in patients with GBC compared to other benign pathologies including gallstone disease. In the tissue sample comparisons, there were 63 and 199 dysregulated proteins in GBC compared to normal and gallstone, respectively. In the plasma comparison, there were 34 altered proteins in GBC compared to the benign biliary pathology group. Pathway analysis showed that the dysregulated proteins in GBC patients were enriched in pathways involved in smooth muscle contraction, metabolism, ECM organization, and integrin cell surface interactions. The identified proteins help in understanding GBC molecular mechanisms in our patient group. Furthermore, the alteration of specific proteins in both tissue and protein samples suggests their potential utility as biomarkers of GBC in this sample cohort

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

SUBMITTER: Previn Naicker  

LAB HEAD: Stoyan Stoychev

PROVIDER: PXD029877 | Pride | 2023-03-11

REPOSITORIES: Pride