Tesis

Analisis mRNA Gen CYP19A1, NR5A1, dan HSD17B2 di Darah Menstruasi dan Studi In Silico Interaksi Gen pada Pasien Endometriosis = Analysis of CYP19A1, NR5A1, and HSD17B2 mRNA in Menstrual Blood and In Silico Study of Gene Interactions in Endometriosis Patients.

Endometriosis merupakan kondisi ginekologi yang dikenal sebagai estrogendependent disesase. Beberapa gen yang terlibat dalam sintesis estrogen, antara lain CYP19A1, NR5A1, dan HSD17B2. Sebagai luruhan dari lapisan endometrium, darah menstruasi merupakan sumber biomarker potensial untuk pengembangan metode diagnostik endometriosis secara noninvasif. Penelitian ini bertujuan untuk menganalisis ekspresi mRNA biomarker CYP19A1, NR5A1, dan HSD17B2 di darah menstruasi dan jaringan endometrium eutopik pada 20 subjek endometriosis dan non-endometriosis. Analisis ekspresi gen dan efektivitas diagnostik dilakukan menggunakan metode quantitative PCR dan kurva ROC. Selain itu, dilakukan studi in silico untuk mengetahui interaksi gen yang terlibat dalam patogenesis endometriosis dan kaitannya dengan sistesis estrogen. Analisis dilakukan terhadap enam dataset Gene Expression Omnibus (GEO), dilanjutkan dengan studi Gene Ontology, pathway enrichment, dan protein-protein interaction (PPI). Hasil analisis ekspresi gen menunjukkan peningkatan CYP19A1, NR5A1, dan HSD17B2 secara signifikan pada darah menstruasi kelompok endometriosis dibandingkan nonendometriosis (P < 0,05). Sementara itu, analisis ekspresi gen di jaringan eutopik hanya ditemukan bermakna pada gen HSD17B2, sedangkan kedua gen lainnya tidak menunjukkan perbedaan signifikan. Adapun area under curve (AUC) pada gen CYP19A1, NR5A1, dan HSD17B2 di darah menstruasi masing-masing adalah 0,977, 0,862, dan 0,807. Berdasarkan studi in silico, diperoleh sebanyak 551 common DEGs yang terdiri atas 292 upregulated dan 259 downregulated genes. Gen-gen tersebut diketahui terlibat dalam berbagai mekanisme patogenesis endometriosis, seperti regulasi siklus sel, interaksi matriks ekstraseluler (ECM), dan adhesi fokal. Sebagai kesimpulan, analisis gen CYP19A1, NR5A1, dan HSD17B2 di darah menstruasi menunjukkan akurasi diagnostik yang baik, dan studi in silico menunjukkan peranan deregulasi siklus sel dalam patogenesis endometriosis yang juga dipengaruhi oleh estrogen.
Kata kunci: CYP19A1, NR5A1, HSD17B2, endometriosis, darah menstruasi, diagnostik


Endometriosis is a gynecology condition known as estrogen-dependent disease. Several genes are involved in estrogen synthesis, including CYP19A1, NR5A1, and HSD17B2. As an endometrial shed, menstrual blood is a potential biomarker source for developing a non-invasive diagnostic method for endometriosis. This study aims to analyze the gene expression of CYP19A1, NR5A1, and HSD17B2 mRNA in menstrual blood compared to eutopic endometrial tissue. The study was conducted on 20 endometriosis and non-endometriosis subjects, where the analysis of gene expression and its diagnostic value were measured using quantitative PCR and ROC curves. In addition, an in silico study was conducted to determine the gene interaction involved in the endometriosis pathogenesis and its relationship to estrogen. The analysis was conducted on six Gene Expression Omnibus (GEO) datasets, followed by Gene Ontology, enrichment pathways, and protein-protein interactions (PPIs) analysis. The gene expression analysis showed a significant increase in CYP19A1, NR5A1, and HSD17B2 levels in the menstrual blood of the endometriosis group compared to non-endometriosis (P < 0.05). Meanwhile, analysis in eutopic tissue was only significant in the HSD17B2 gene, while the other two genes did not show significant differences. The area under the curve (AUC) of the CYP19A1, NR5A1, and HSD17B2 in menstrual blood were 0.977, 0.862, and 0.807, respectively. Based on the in silico study, 551 common DEGs were obtained, consisting of 292 upregulated genes and 259 downregulated genes. These genes are involved in various endometriosis pathogenesis, such as cell cycle regulation, extracellular matrix (ECM) interactions, and focal adhesion. In conclusion, analysis of CYP19A1, NR5A1, and HSD17B2 in menstrual blood showed good diagnostic accuracy, and in silico studies suggest a role for cell cycle deregulation in the pathogenesis of endometriosis which is also influenced by estrogen.
Key words: CYP19A1, NR5A1, HSD17B2, diagnostic, endometriosis, menstrual blood