Assesement of serum Sfrp5/Wnt-5a level and its utility in the risk stratification of treatment naïve patients with metabolic syndrome

Yadav, Suraj Singh; Hussain, Sartaj; Dwivedi, Pradeep; Khattri, Sanjay; Sawlani, Kamal Kumar; Usman, Kauser

doi:10.1080/15321819.2022.2104125

Cited by 4 publications

(2 citation statements)

References 26 publications

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“…There was no significant difference between stage I and IV. Recognising the notable variations in both age and sex among our patient cohorts and considering prior studies indicating the potential impact of these factors on cSFRP5 levels 30,31 , we utilised a linear regression model to account for age and sex differences (Supplementary Table 5). Our analysis revealed a correlation between age and increased cSFRP5 concentration, but no discernible disparity was observed between males and females.…”

Section: Resultsmentioning

confidence: 99%

Circulating SFRP5 levels are elevated in colorectal cancer and correlate with overall survival in stage II-III disease

Li,

Liu,

Yeo

et al. 2024

Preprint

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Secreted Frizzled-Related Protein 5 (SFRP5) modulates Wnt signalling pathways, affecting diverse biological processes. We assessed the diagnostic and prognostic value of circulating SFRP5 (cSFRP5) in colorectal cancer (CRC). Plasma cSFRP5 concentrations were measured using ELISA in healthy donors (n=133), individuals diagnosed with CRC (n=449), colorectal polyps (n=85), and medical conditions in other organs including cancer, inflammation, and benign states (n=64). Patients with CRC, polyps, and other conditions showed higher cSFRP5 levels than healthy individuals (p<0.0001). Receiver operating characteristic curves comparing healthy donors with medical conditions, polyps, and CRC were 0.814 (p<0.0001), 0.763 (p<0.0001), and 0.762 (p<0.0001), respectively. In CRC, cSFRP5 correlated with patient age (p<0.0001), tumour stage (p<0.0001), and histological differentiation (p=0.0273). Levels peaked in stage II versus I (p<0.0001), III (p=0.0007), or IV (p<0.0001), and were higher in stage III versus I (p=0.0007) and IV (p=0.0054), with no difference between I and IV. Elevated cSFRP5 levels predicted longer overall survival in stage II-III CRC (univariate: HR 1.82, 95% CI 1.02-3.26, p=0.024; multivariable: HR 2.34, 95% CI 1.12-4.88, p=0.015). This study confirms elevated cSFRP5 levels in CRC and reveals a correlation between elevated cSFRP5 and overall survival in stage II-III disease.

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Section: Resultsmentioning

confidence: 99%

Circulating SFRP5 levels are elevated in colorectal cancer and correlate with overall survival in stage II-III disease

Li,

Liu,

Yeo

et al. 2024

Preprint

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“…Hyperactivation of the Wnt5a pathway in monocytes has been proposed to be a key mechanism through which metabolic syndrome patients 2 have impaired collateralisation [3][4][5] . In T2D and in obesity circulating monocytes are pro-inflammatory 6 .…”

Section: Introductionmentioning

confidence: 99%

The splicing factor kinase SRPK1 is a therapeutic target for Peripheral Vascular Disease

Bhalla,

Wahid,

Amartey

et al. 2024

Preprint

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VEGF-A splicing has been shown to be regulated in cancer and epithelial cells by phosphorylation of serine/arginine splicing factor 1 (SRSF1) by serine-arginine protein kinase 1 (SRPK1). In these cell types inhibition of SRPK1 switches splicing to the anti-angiogenic VEGF-A isoforms. In peripheral arterial disease (PAD) the anti-angiogenic isoform of VEGF-A, VEGF-A165b, is overexpressed in circulating monocytes. To determine control of VEGF splicing in monocytes, we investigated the effects of SRPK1 inhibition and monocyte-specific SRPK1 knockout in mouse models of PAD and in human monocytes from patients with PAD. VEGF-A165b activity was measured in monocytes from patients with PAD by co-culture with endothelial cells in a migration assay in the presence of SRPK1 inhibitors. Mice with impaired revascularisation due to either soluble frizzled related protein 5 knockout (Sfrp5-/-), monocyte-specific gain-of-function of Wnt5a (LysM-Wnt5aGOF), or obese mice on a high fat high sucrose (HF/HS) diet were subjected to femoral artery ligation and treated with SRPK1 inhibitor SPHINX31. To determine monocyte specific SRPK1 activity we generated an SRPK1 conditional knockout under control of a monocyte specific (LysM-Cre) driver (SRPK1MoKO). Paw blood flow was measured by Laser Speckle Imaging before, and for 28 days after, surgery. Results. Monocytes from patients with PAD significantly inhibited migration of human endothelial cells in culture, which was inhibited by an anti-VEGF-A165b antibody. Surprisingly, this inhibition was reversed by SRPK1 inhibition, which switched splicing from VEGF-A165b to VEGF-A165a. In the Sfrp5-/-, LysM-Wnt5aGOF and HF/HS mouse models of PAD, impaired blood flow was reversed by SRPK1 inhibition. The impaired revascularisation in LysM-Wnt5aGOF mice was also rescued in LysM-Wnt5aGOF:SRPK1MoKO mice. Impaired blood flow recovery was also rescued in obese-SRPK1MoKO mice. Conclusion. VEGF splicing in monocytes is differently regulated from VEGF splicing in epithelial cells or cancer cells. This indicates that control of splicing is dependent on cell type and/or environment.

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Secreted frizzled-related protein 5: A promising therapeutic target for metabolic diseases via regulation of Wnt signaling

Song

Zhang

et al. 2023

Biochemical and Biophysical Research Communications

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Assesement of serum Sfrp5/Wnt-5a level and its utility in the risk stratification of treatment naïve patients with metabolic syndrome

Cited by 4 publications

References 26 publications

Circulating SFRP5 levels are elevated in colorectal cancer and correlate with overall survival in stage II-III disease

Circulating SFRP5 levels are elevated in colorectal cancer and correlate with overall survival in stage II-III disease

The splicing factor kinase SRPK1 is a therapeutic target for Peripheral Vascular Disease

Secreted frizzled-related protein 5: A promising therapeutic target for metabolic diseases via regulation of Wnt signaling

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