Tesis

Ekspresi gen Dickkopf 1 (DKK1), R-Spondin 3 (RSPO3) dan Catenin Beta-1 (CTNNB1) dalam patogenesis polip endometrium melalui jalur pensinyalan Wnt/ β-catenin : Studi komparatif terhadap jaringan endometrium berdekatan = Expression of Dickkopf 1 (DKK1), R-Spondin 3 (RSPO3) and Catenin Beta-1 (CTNNB1) in the pathogenesis of endometrial polyps through Wnt/ β-Catenin signaling pathway : A comparative study with adjacent endometrial tissue.

Latar Belakang: Polip endometrium adalah pertumbuhan fokal abnormal pada endometrium yang dapat menyebabkan perdarahan uterus abnormal dan infertilitas. Jalur pensinyalan Wnt/β-catenin berperan penting dalam regulasi proliferasi dan diferensiasi sel endometrium. Gen Dickkopf-1 (DKK1) sebagai inhibitor, serta R-spondin 3 (RSPO3) sebagai aktivator Wnt/β-catenin, diduga memengaruhi ekspresi CTNNB1 dan berkontribusi dalam patogenesis polip endometrium. Namun, keterlibatan ketiga gen ini belum sepenuhnya dipahami. Tujuan: Menganalisis ekspresi gen DKK1, RSPO3, dan CTNNB1 serta korelasinya pada jaringan polip endometrium dan jaringan endometrium yang berdekatan. Metode: Penelitian potong lintang ini melibatkan 31 subjek yang menjalani histeroskopi polipektomi. Sampel jaringan polip dan jaringan endometrium sekitar dianalisis ekspresi gen DKK1, RSPO3, dan CTNNB1 menggunakan RT-qPCR. Uji Wilcoxone signed rank-test digunakan untuk membandingkan ekspresi gen antar jaringan, dan korelasi Spearman digunakan untuk menilai hubungan antar ekspresi gen. Hasil: Terdapat perbedaan bermakna ekspresi gen DKK1 (z = -2,450; p = 0,014), Tidak terdapat perbedaan bermakna pada ekspresi gen RSPO3 (z = -0,470; p = 0,638) dan CTNNB1 (z = -1,548; p = 0,122) antara jaringan polip endometrium dan jaringan endometrium yang berdekatan. Terdapat korelasi positif yang bermakna antara ekspresi gen DKK1 dan CTNNB1 di jaringan polip (r = 0,628; p < 0,001 ) dan di jaringan endometrium yang berdekatan (r = 0,410; p = 0,022). Terdapat korelasi positif bermakna antara ekspresi gen RSPO3 dan CTNNB1 pada jaringan polip (r = 0,527; p = 0,002) dan jaringan endometrium yang berdekatan (r = 0,416; p = 0,020). Kesimpulan: Jalur pensinyalan Wnt/β-catenin berperan dalam patogenesis polip endometrium melalui regulasi ekspresi gen DKK1, RSPO3, dan CTNNB1
Kata Kunci: Polip endometrium, DKK1, RSPO3, CTNNB1, Wnt/β-catenin, ekspresi gen


Background: Endometrial polyps are focal abnormal growths of the endometrium frequently observed in reproductive-aged women and may lead to abnormal uterine bleeding and infertility. The Wnt/β-catenin signaling pathway plays a crucial role in regulating proliferation and differentiation of endometrial cells. Dickkopf-1 (DKK1), an inhibitor, and R-spondin 3 (RSPO3), an activator of the Wnt/β-catenin pathway, are hypothesized to influence the expression of CTNNB1 (β-catenin) and contribute to the pathogenesis of endometrial polyps. However, the exact roles of these genes remain unclear. Objective: To assess the expression of DKK1, RSPO3, and CTNNB1 genes and their correlations in endometrial polyp tissue and adjacent normal endometrial tissue to better understand their involvement in Wnt/β-catenin pathway regulation. Methods: This cross-sectional study involved 31 subjects who underwent operative hysteroscopic polypectomy. Paired samples of polyp and adjacent endometrial tissues were analyzed for DKK1, RSPO3, and CTNNB1 gene expression using RTqPCR. Wilcoxon signed rank-test were used to compare gene expression between tissues, while spearman correlation was used to assess inter-gene expression relationships. Results: There was a significant difference in DKK1 gene expression (z = -2.450; p = 0.014), while no significant difference was observed in RSPO3 (z = -0.470; p = 0.638) and CTNNB1 (z = -1.548; p = 0.122) gene expression between endometrial polyp tissue and adjacent endometrial tissue. A significant positive correlation was found between DKK1 and CTNNB1 expression in polyp tissue (r = 0.628; p < 0.001) as well as in adjacent endometrial tissue (r = 0.410; p = 0.022). Additionally, a significant positive correlation between RSPO3 and CTNNB1 expression was also observed in both polyp tissue (r = 0.527; p = 0.002) and adjacent endometrial tissue (r = 0.416; p = 0.020) Conclusion: The Wnt/β-catenin signalling pathway plays a role in the pathogenesis of endometrial polyps through the regulation of DKK1, RSPO3, and CTNNB1 gene expression
Keywords: Endometrial polyp, DKK1, RSPO3, CTNNB1, Wnt/β-catenin, gene expression.