İLK TEDAVİ DEĞERLERİNE DAYALI ROMATOİD ARTRİTTE BİYOBELİRTEÇ KÜMELERİNİN DEĞERLENDİRİLMESİ

Öz

Romatoid artrit (RA), sistemik inflamasyonla karakterize, eklem hasarına ve sistemik komplikasyonlara yol açan kronik bir otoimmün hastalıktır. Bu çalışma, GEO2R veritabanından elde edilen gen ifadesi verilerini kullanarak RA hastalarında biyobelirteç kümelerini ilk tedavi yanıtlarına göre değerlendirmeyi amaçlamaktadır. 104 gen beş işlevsel kategoriye ayrılmıştır: otoimmünite, inflamasyon, hastalık ilerlemesi, doku hasarı ve tedavi yanıtı. Kümeleme analizi, metotreksat (MTX) ve biyolojik tedaviler ile tedavi edilen hastalar arasında gen ifadesi örüntülerinde anlamlı farklılıklar ortaya koymuştur. Bulgularımız, RA patogenezinde inflamasyonun baskın rolünü vurgulamakta ve kişiselleştirilmiş tedavi stratejileri için bir çerçeve sunmaktadır. Hiyerarşik kümeleme analizi, inflamasyonla ilişkili genlerin (IL6ST, RNF146) en yüksek transkripsiyonel koordinasyonu gösterdiğini belirlemiştir. Yüksek düzeyde eksprese edilen genler (RNA45SN1, MALAT1, TMEM259) ribozom biyogenezi, sinovyal yeniden yapılanma ve sitokin sinyalleşmesi ile ilişkilendirilmiştir. Otoimmünite ile ilişkili (RO60, MBD6) ve tedavi yanıtı belirteçleri (TRIM41, PPP1R12C) ayrı kümeler oluşturmuştur. Dendrogram analizi, IL6ST aracılı yolakları ve MALAT1’e bağlı doku hasarı mekanizmalarını merkezi düğümler olarak öne çıkarmıştır. Kümeleme örüntüleri metotreksat ve biyolojik tedavi gören gruplar arasında farklılık göstermiş; ikincisinde inflamasyon ve doku onarımı genlerinin (MUS81, TMED7) daha sıkı düzenlendiği görülmüştür. Çalışma, RA heterojenitesinin anlaşılmasında ve tedavi sonuçlarının iyileştirilmesinde biyobelirteçlerin önemini vurgulamaktadır.

Anahtar Kelimeler

• Romatoid artrit
• Biyobelirteç kümeleme
• Gen ifadesi
• Hiyerarşik kümeleme

EVALUATİNG BİOMARKER CLUSTERS İN RHEUMATOİD ARTHRİTİS BASED ON FİRST-TREAT VALUES

Öz

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic inflammation, leading to joint damage and systemic complications. This study aims to evaluate biomarker clusters in RA patients based on their initial treatment responses, using gene expression data from the GEO2R database. We classified 104 genes into five functional categories: autoimmunity, inflammation, disease progression, tissue damage, and treatment response. Clustering analysis revealed significant differences in gene expression patterns between patients treated with methotrexate (MTX) and biological therapies. Our findings highlight the dominant role of inflammation in RA pathogenesis and provide a framework for personalized treatment strategies. Hierarchical clustering analysis identified inflammation-related genes (IL6ST, RNF146) as exhibiting the highest transcriptional coordination. Highly expressed genes (RNA45SN1, MALAT1, TMEM259) were associated with ribosomal biogenesis, synovial remodeling, and cytokine signaling. Autoimmunity-related (RO60, MBD6) and treatment response markers (TRIM41, PPP1R12C) formed distinct clusters. Dendrogram analysis highlighted IL6ST-mediated pathways and MALAT1-dependent tissue damage mechanisms as central nodes. Clustering patterns differed between methotrexate- and biologic-treated cohorts, with the latter showing tighter regulation of inflammation and tissue repair genes (MUS81, TMED7). The study underscores the importance of biomarkers in understanding RA heterogeneity and improving therapeutic outcomes.

Anahtar Kelimeler

• Rheumatoid arthritis
• Biomarker clustering
• Gene expression
• Hierarchical clustering

Kaynakça

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