The GPR35 expression pattern is associated with overall survival in male patients with colorectal cancer

Mackiewicz, Tomasz; Jacenik, Damian; Talar, Marcin; Fichna, Jakub

doi:10.1007/s43440-022-00371-2

Cited by 6 publications

(5 citation statements)

References 35 publications

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“…13 Importantly, the relative GPR35 expression can already be found in the publicly available databases, such as the TCGA PanCancerAtlas, and there are reports available about statistically significant shorter OS in patients with positive GPR35 Z-score based on these data -the recent concerning males with CRC and PDAC. 12 To confirm the correlation between GPR35 mRNA relative expression and development of PDAC or CRC, we performed laboratory investigation of tumor samples from patients with advanced PDAC or CRC who were undergoing surgery for their primary diagnosis. From a group of patients with CRC, we also collected healthy samples.…”

Section: Discussionmentioning

confidence: 99%

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Increased GPR35 expression in human colorectal and pancreatic cancer samples: A preliminary clinical validation of a new biomarker

et al. 2023

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Background. G protein-coupled receptor 35 (GPR35) is involved in carcinogenesis; however, limited experimental data are available on its actual expression in patients with colorectal cancer (CRC) and pancreatic adenocarcinoma (PDAC).Objectives. We aimed to measure the relative expression of GPR35 in samples from patients with CRC or PDAC. Materials and methods.Using real-time polymerase chain reaction (RT-PCR), we have examined GPR35 expression in surgery samples from 40 CRC and 17 PDAC patients, and performed analysis of the results.Results. The analysis of GPR35 expression in patients with CRC revealed correlations between relative GPR35 mRNA expression and several tumor characteristics, with statistical significance for higher American Joint Committee on Cancer (AJCC) stages, T stages and histological grades. GPR35 expression was significantly higher in tumor samples compared to the paired healthy samples collected from the same patient. Similar, although not statistically significant trends were found in PDAC tumor samples for sex (lower expression in women) and for samples with no nodal involvement (lower expression). Samples with higher tumor T stages and higher histological grades or considered inoperable had higher GPR35 expression. Conclusions.We have identified correlations which confirm our expectation of high GPR35 expression in CRC and PDAC. Our findings suggest the prognostic value of GPR35 testing in patients with an increased risk of CRC or PDAC development, and warrant further clinical confirmation.

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Section: Discussionmentioning

confidence: 99%

“…The performed analysis showed a negative association between positive GPR35 expression Z-score and OS in males, which remains statistically significant in advanced stages of CRC, suggesting the prognostic value of early testing of GPR35 in male patients with an increased risk of CRC development. 12…”

Section: Introductionmentioning

confidence: 99%

Increased GPR35 expression in human colorectal and pancreatic cancer samples: A preliminary clinical validation of a new biomarker

et al. 2023

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“…There have been more publications alluding to potential links between GPR35 and cancer than to any other disease set. These range from correlations in expression of GPR35 with progression and stage of various cancers [38], analysis to suggest that high level expression of the long GPR35b isoform (Box 3) in lymph nodes of colon cancer patients is associated with poor prognosis [64][65], or maybe that expression of GPR35 is positively linked to survival [39]. Mice lacking GPR35 develop less intestinal tumours in spontaneous and inflammation-induced cancer models [61].…”

Section: Gpr35 As a Target In Oncologymentioning

confidence: 99%

“…Links between GPR35 levels and outcomes in intestinal and other cancers have been established with prognosis and survival inversely correlated with expression levels [38][39][40][64][65]. Higher levels of GPR35 may promote hyperplasia with subsequent angiogenesis [61,66] and metastasis.…”

Section: Figure 1b Gpr35 As a Prognostic And Potential Therapeutic In...mentioning

confidence: 99%

GPR35: from enigma to therapeutic target

Milligan

2023

Trends in Pharmacological Sciences

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“…GPR35, a member of the G protein-coupled receptors family, is considered an orphan receptor whose precise physiological function and endogenous ligand are under intensive investigation ( De Giovanni et al, 2022 ; Sun et al, 2022 ; Wyant et al, 2022 ). GPR35 was found to be implicated in cancer development by numerous studies, especially in colon cancer ( Ali et al, 2019 ; Hao et al, 2022 ; Mackiewicz et al, 2022 ), but the underlying mechanism is unclear. Recently, a constitutive ligand-independent pro-cancer function of GPR35 was reported, demonstrating that GPR35 interacted with Na + /K + -ATPase inducing colorectal cancer (CRC) cell proliferation and glycolysis ( Schneditz et al, 2019 ), also driving macrophages to promote angiogenesis in the tumor microenvironment ( Pagano et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

GPR35 antagonist CID-2745687 attenuates anchorage-independent cell growth by inhibiting YAP/TAZ activity in colorectal cancer cells

et al. 2023

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Background and purpose: GPR35, a member of the orphan G-protein-coupled receptor, was recently implicated in colorectal cancer (CRC). However, whether targeting GPR35 by antagonists can inhibit its pro-cancer role has yet to be answered.Experimental approach: We applied antagonist CID-2745687 (CID) in established GPR35 overexpressing and knock-down CRC cell lines to understand its anti-cell proliferation property and the underlying mechanism.Key results: Although GPR35 did not promote cell proliferation in 2D conditions, it promoted anchorage-independent growth in soft-agar, which was reduced by GPR35 knock-down and CID treatment. Furthermore, YAP/TAZ target genes were expressed relatively higher in GPR35 overexpressed cells and lower in GPR35 knock-down cells. YAP/TAZ activity is required for anchorage-independent growth of CRC cells. By detecting YAP/TAZ target genes, performing TEAD4 luciferase reporter assay, and examining YAP phosphorylation and TAZ protein expression level, we found YAP/TAZ activity is positively correlated to GPR35 expression level, which CID disrupted in GPR35 overexpressed cells, but not in GPR35 knock-down cells. Intriguingly, GPR35 agonists did not promote YAP/TAZ activity but ameliorated CID’s inhibitory effect; GPR35-promoted YAP/TAZ activity was only partly attenuated by ROCK1/2 inhibitor.Conclusion and implications: GPR35 promoted YAP/TAZ activity partly through Rho-GTPase with its agonist-independent constitutive activity, and CID exhibited its inhibitory effect. GPR35 antagonists are promising anti-cancer agents that target hyperactivation and overexpression of YAP/TAZ in CRC.

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The GPR35 expression pattern is associated with overall survival in male patients with colorectal cancer

Cited by 6 publications

References 35 publications

Increased GPR35 expression in human colorectal and pancreatic cancer samples: A preliminary clinical validation of a new biomarker

Increased GPR35 expression in human colorectal and pancreatic cancer samples: A preliminary clinical validation of a new biomarker

GPR35: from enigma to therapeutic target

GPR35 antagonist CID-2745687 attenuates anchorage-independent cell growth by inhibiting YAP/TAZ activity in colorectal cancer cells

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