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

Znanstveni rad - Izvorni znanstveni rad

• Autor: Maja Sremac
• Autor: Frane Paić
• Autor: Katja Ravić
• Autor: Ljiljana Šerman
• Autor: Aja Pavičić Dujmović
• Autor: Iva Brčić
• Autor: Željko Krznarić; MBZ: 75865
• Autor: Tamara Martić
• Autorova ustanova: Sveučilište u Zagrebu; Medicinski fakultet; (KATEDRA ZA INTERNU MEDICINU)
• Autorova ustanova: Sveučilište u Zagrebu; Medicinski fakultet; (KATEDRA ZA MEDICINSKU BIOLOGIJU)
• Znanstveno / umjetničko područje, polje i grana: BIOMEDICINA I ZDRAVSTVO; Kliničke medicinske znanosti; Interna medicina
• Znanstveno / umjetničko područje, polje i grana: BIOMEDICINA I ZDRAVSTVO; Temeljne medicinske znanosti; Citologija, histologija i embriologija

Sažetak (engleski)

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.

• Ključne riječi (engleski): DVL2; DVL3; SFRP1; SFRP3; Wnt signaling pathway; diffuse gastric carcinoma
• Jezik: engleski
• Vrsta publikacije: Znanstveni rad - Izvorni znanstveni rad
• Status objave: Objavljen
• Vrsta recenzije: Recenziran
• Verzija publikacije: Objavljena verzija rada (izdavačev PDF)
• Naslov časopisa: Oncology Letters
• Brojčani podaci: vol. 22, br. 6, 822
• p-ISSN: 1792-1074
• e-ISSN: 1792-1082
• DOI: https://doi.org/10.3892/ol.2021.13083
• URN:NBN: urn:nbn:hr:105:791452
• Datum objave publikacije: 2021-10-08
• Projekt: Šifra: KK.01.1.1.01.0008; Naziv (hrvatski): Znanstveni centar izvrsnosti za reproduktivnu i regenerativnu medicinu – istraživanja novih platformi i potencijala; Naziv (engleski): Reproductive, and Regenerative Medicine-Exploring New Platforms and Potentials; Kratica: CERRM; Voditelj: Slobodan Vukičević; Pravna nadležnost: eu; Financijer: EK
• URL dokumenta: http://www.spandidos-publications.com/10.3892/ol.2021.13083
• Vrsta resursa: Tekst
• Prava pristupa: Otvoreni pristup
• Datum i vrijeme pohrane: 2022-04-01 08:24:37