Aberrant expression of SFRP1, SFRP3, DVL2 and DVL3 Wnt signaling pathway components in diffuse gastric carcinoma

Sremac,Maja; Paic,Frane; Grubelic Ravic,Katja; Serman,Ljiljana; Pavicic Dujmovic,Aja; Brcic,Iva; Krznaric,Zeljko; Nikuseva Martic,Tamara

doi:10.3892/ol.2021.13083

Aberrant expression of SFRP1, SFRP3, DVL2 and DVL3 Wnt signaling pathway components in diffuse gastric carcinoma

Authors:
- Maja Sremac
- Frane Paic
- Katja Grubelic Ravic
- Ljiljana Serman
- Aja Pavicic Dujmovic
- Iva Brcic
- Zeljko Krznaric
- Tamara Nikuseva Martic
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Affiliations: Division of Gastroenterology and Hepatology, University Hospital Center, 10000 Zagreb, Croatia, Laboratory for Epigenetics and Molecular Medicine, Department of Medical Biology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia, Department of Medical Biology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia, Department of Radiology, General Hospital ‘Dr. Ivo Pedisic’, 44000 Sisak, Croatia, Diagnostic and Research Institute of Pathology, Medical University of Graz, A‑8010 Graz, Austria
Published online on: October 8, 2021 https://doi.org/10.3892/ol.2021.13083
Article Number: 822
Copyright: © Sremac et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Diffuse gastric carcinoma (DGC) is characterized by poorly cohesive cells, highly invasive growth patterns, poor prognosis and resistance to the majority of available systemic therapeutic strategies. It has been previously reported that the Wnt/β‑catenin signaling pathway serves a prominent role in the tumorigenesis of gastric carcinoma. However, the mechanism underlying the dysregulation of this pathway in DGC has not been fully elucidated. Therefore, the present study aimed to investigate the expression profiles of Wnt antagonists, secreted frizzled‑related protein 1 (SFRP1) and secreted frizzled‑related protein 3 (SFRP3), and dishevelled protein family members, dishevelled segment polarity protein 2 (DVL2) and dishevelled segment polarity protein 3 (DVL3), in DGC tissues. The association between the expression levels of these factors and the clinicopathological parameters of the patients was determined. Protein and mRNA expression levels in 62 DGC tumor tissues and 62 normal gastric mucosal tissues obtained from patients with non‑malignant disease were measured using immunohistochemical and reverse transcription‑quantitative PCR (RT‑qPCR) analysis. Significantly lower protein expression levels of SFRP1 (P<0.001) and SFRP3 (P<0.001), but significantly higher protein expression levels of DVL2 (P<0.001) and DVL3 (P<0.001) were observed in DGC tissues compared with in control tissues by immunohistochemistry. In addition, significantly lower expression levels of SFRP1 (P<0.05) and higher expression levels of DVL3 (P<0.05) were found in in DGC tissues compared with those in normal gastric mucosal tissues using RT‑qPCR. According to correlation analysis between the SFRP1, SFRP3, DVL2 and DVL3 protein expression levels and the clinicopathological characteristics of patients with DGC, a statistically significant correlation was found between the SFRP3 volume density and T stage (r=0.304; P=0.017) and between the SFRP3 volume density and clinical stage (r=0.336; P=0.008). In conclusion, the findings of the present study suggested that the Wnt signaling pathway components SFRP1, SFRP3, DVL2 and DVL3 may be aberrantly expressed in DGC tissues, implicating their possible role in the development of this malignant disease. The present data also revealed a positive relationship between SFRP3 protein expression and the clinical and T stage of DGC.

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