The role of G protein-coupled receptor 35 in the development and progression of colorectal cancer

Nazeer, Shakeera (2026) The role of G protein-coupled receptor 35 in the development and progression of colorectal cancer. MSc(R) thesis, University of Glasgow.

Abstract

G protein-coupled receptor 35 (GPR35) has emerged as a potential biomarker across multiple malignancies, including inflammatory bowel disease (IBD) and colorectal cancer (CRC). As CRC is one of the most common causes of cancer-related deaths globally, further investigation into clinically relevant biomarkers is necessary. This study aimed to determine whether GPR35 protein expression is associated with colorectal cancer disease progression. This question was addressed by determining if GPR35 expression is associated with patient prognosis relative to different genetic, molecular, and histological backgrounds. In this thesis, firstly, a meta-analysis was carried out to survey the current literature and to establish the prognostic value of GPR35 expression in solid cancers. GPR35 was shown to have a tissue context dependent role, but there were no consistent findings if expression was protective or detrimental to patient prognosis in CRC. Additionally, two anti-GPR35 antibodies were identified through the meta-analysis and subjected to antibody specificity testing. The Abcam ab188949 antibody was then optimised for the use in Immunohistochemical (IHC) detection of GPR35 expression in formalin-fixed paraffin embedded (FFPE) tissue. The study found that high expression of GPR35 within the cytoplasm was associated with reduced cancer-specific survival in CRC, particularly in patients with right-sided disease. In contrast, high expression of GPR35 within the membrane was associated with improved survival in CRC patients but only in left sided disease, TNM III, GMS1 and mGPS1. This highlighted the importance of cellular localisation of GPR35 in the tumour cell. Tempo-Seq analysis of a small subset of these patients was unable to reveal a definitive mechanism for the poor outcomes seen in the high cytoplasmic expression group. Overall, this study could indicate that current molecular subtyping does not capture the anti-proliferative group that GPR35 may belong to. GPR35 expression may be prognostically significant in a specific context of CRC progression; however, this remains to be inconclusive. One of the key findings of this study was that cellular localisation of GPR35 in the tumour cell has vastly different effects on patient survival. Further validation and mechanistic studies are required before GPR35 can be considered as a contributor to the development of CRC, as well as a new prognostic marker with clinical impact.

• Item Type: Thesis (MSc(R))
• Qualification Level: Masters
• Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Supervisor's Name: McCall, Dr. Pamela and Edwards, Professor Joanne
• Date of Award: 2026
• Depositing User: Theses Team
• Unique ID: glathesis:2026-86202
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 27 Aug 2026 15:18
• Last Modified: 27 Aug 2026 15:20
• Thesis DOI: 10.5525/gla.thesis.86202
• URI: https://theses.gla.ac.uk/id/eprint/86202