Proteomic analysis identifies dysregulated proteins and associated molecular pathways in a cohort of gallbladder cancer patients of African ancestry

Pavan Baichan; Previn Naicker; Tanya Nadine Augustine; Martin Smith; Geoffrey Candy; John Devar; Ekene Emmanuel Nweke

doi:10.1186/s12014-023-09399-9

Proteomic analysis identifies dysregulated proteins and associated molecular pathways in a cohort of gallbladder cancer patients of African ancestry

Clin Proteomics. 2023 Mar 1;20(1):8. doi: 10.1186/s12014-023-09399-9.

Authors

Pavan Baichan¹, Previn Naicker², Tanya Nadine Augustine³, Martin Smith^{1

4}, Geoffrey Candy¹, John Devar^{1

4}, Ekene Emmanuel Nweke⁵

Affiliations

¹ Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road Parktown, Johannesburg, 2193, South Africa.
² Council for Scientific and Industrial Research, Pretoria, 0001, South Africa.
³ School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa.
⁴ Hepatopancreatobiliary Unit, Department of Surgery, Chris Hani-Baragwanath Academic Hospital, Soweto, Johannesburg, South Africa.
⁵ Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road Parktown, Johannesburg, 2193, South Africa. Ekene.Nweke@wits.ac.za.

Abstract

Background: 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.

Methods: Tissues (27 GBC, 13 Gallstone disease, and 5 normal tissues) and blood plasma (54 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.

Results: In the tissue sample group, there were 62 and 194 dysregulated proteins in GBC compared to normal and gallstone groups, respectively. In the plasma group, there were 33 altered proteins in GBC compared to the benign biliary pathology group. We found 9 proteins (APOA1, APOA2, RET4, TTR, HEMO, HBB, HBA, PIGR, and APOE) to be commonly dysregulated in both tissue and plasma. Furthermore, a subset analysis demonstrated that 2 proteins, S100A8 and S100A9, were downregulated in GBC patients with GD history compared to those without. 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.

Conclusion: The identified dysregulated proteins help in understanding GBC molecular mechanisms in our patient group. Furthermore, the alteration of specific proteins in both tissue and plasma samples suggests their potential utility as biomarkers of GBC in this sample cohort.

Keywords: Gallbladder cancer; Gallstone disease; Molecular pathways; Proteins; SWATH-MS.