Geç başlangıçlı alzheimer hastalığı ve hepatosellüler karsinom ile ilişkili ortak moleküler yolakların ve anahtar biyobelirteçlerin biyoinformatik analizlerle araştırılması
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Date
2020-07-08
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Bursa Uludağ Üniversitesi
Abstract
Son zamanlardaki çalışmalarda Alzheimer hastalığı (AH) ve kanser arasında bir bağlantı olduğu ortaya konmuş fakat ortak mekanizmayı açıklayacak yeterince kanıt mevcut değildir. Bu bağlantıyı araştıran birçok çalışmada özellikle meme, prostat ve akciğer gibi kanser türleri ile AH arasında ters ilişki olduğu gösterilmekle beraber hepatosellüler karsinom (HCC) ve AH arasındaki ilişki henüz aydınlatılmamıştır. Bu çalışmada, geç başlangıçlı AH (LOAD) ve HCC ile ilişkili RNA dizileme (RNA-seq) verilerini biyoinformatik araçlarla analiz ederek iki hastalığın patogenezinde etkin olması muhtemel ortak moleküler yolakları, ortak diferansiyel olarak ifade olan genleri (DEG) ve aday anahtar miRNA’ları tespit etmeyi amaçladık. RNA-seq veri setleri NCBI-GEO veri tabanından alınarak GREIN web uygulaması ile analiz edildi. Ortak DEG’ler tespit edilerek, fonksiyon zenginleştirme analizleri NetworkAnalyst ile yapıldı. Network görselleştirme ve hub gen tespiti Cytoscape programı ile gerçekleştirildi. Hub genleri hedef alan miRNA’lar mirDIP veri tabanı ile belirlendi. Analiz sonucunda iki veri setinde ortak disregüle olan 33 DEG tespit edildi ve network analizinde iki hastalığın moleküler etiyolojisinde olası rolü olan ortak 5 hub gen (HLA-A, HLA-C, TRIM31, HLA-DQB2, HLA-DRB) belirlendi. Ortak DEG'lerin immun sistemle ilişkili moleküler yolaklarda ve biyolojik süreçlerde etkin olduğunu gözlemlendi. Ortak hub genlerin koregülasyonunda potansiyel düzenleyici rolleri olabilecek iki hastalıkla da ilişkili olduğu tahmin edilen birçok miRNA bulundu. Sonuçlarımız, her iki hastalık için risk değerlendirmesi ve ilaç geliştirme yaklaşımları için kullanılabilecek ortak moleküler mekanizmayı in silico kanıtlarla vurgulamaktadır.
Recent studies suggest a potential link between Alzheimer's disease (AD) and cancer yet lack of evidence exists to understand the shared mechanism underlying both diseases. Accumulating research investigating the association between AD and specific types of cancers such as breast, lung and prostate cancer claim inverse relationship between them however possible molecular relationship between AD and hepatocellular carcinoma (HCC) has not been well studied. In this study, we reanalyzed RNA-sequencing data sets related to late-onset AD (LOAD) and HCC to identify common differentially expressed genes (DEGs), molecular pathways as well as key miRNA regulators that may involve in the pathogenesis of both diseases. The data sets were retrieved from NCBI-GEO database and analyzed by GREIN web tool. Overlapped DEGs were identified and their functional enrichments were analyzed by NetworkAnalyst. Cytoscape software was used to visualize network and identify hub genes. MicroRNAs targeting the hub genes were also determined by mirDIP database. A total of 33 DEGs were found to be dysregulated in both datasets and five genes (HLA-A, HLA-C, TRIM31, HLA-DQB2, HLA-DRB1) were identified as hub genes that possibly involve in the shared molecular etiology of both diseases. Our analyses revealed that common DEGs are enriched in molecular pathways related immune system and multiple miRNA regulators are likely to coregulate the expressions of shared hub genes. The results emphasize in silico evidence of common molecular background for LOAD and HCC, which can be ultimately utilized for risk assessments and drug development approaches for both diseases.
Recent studies suggest a potential link between Alzheimer's disease (AD) and cancer yet lack of evidence exists to understand the shared mechanism underlying both diseases. Accumulating research investigating the association between AD and specific types of cancers such as breast, lung and prostate cancer claim inverse relationship between them however possible molecular relationship between AD and hepatocellular carcinoma (HCC) has not been well studied. In this study, we reanalyzed RNA-sequencing data sets related to late-onset AD (LOAD) and HCC to identify common differentially expressed genes (DEGs), molecular pathways as well as key miRNA regulators that may involve in the pathogenesis of both diseases. The data sets were retrieved from NCBI-GEO database and analyzed by GREIN web tool. Overlapped DEGs were identified and their functional enrichments were analyzed by NetworkAnalyst. Cytoscape software was used to visualize network and identify hub genes. MicroRNAs targeting the hub genes were also determined by mirDIP database. A total of 33 DEGs were found to be dysregulated in both datasets and five genes (HLA-A, HLA-C, TRIM31, HLA-DQB2, HLA-DRB1) were identified as hub genes that possibly involve in the shared molecular etiology of both diseases. Our analyses revealed that common DEGs are enriched in molecular pathways related immune system and multiple miRNA regulators are likely to coregulate the expressions of shared hub genes. The results emphasize in silico evidence of common molecular background for LOAD and HCC, which can be ultimately utilized for risk assessments and drug development approaches for both diseases.
Description
4.Çukurova Hepatoselüler Karsinoma Kongresi’nde (2729 Şubat 2020, Adana) sözlü bildiri olarak sunulmuştur.
Keywords
Alzheimer Hastalığı, Hepatosellüler karsinom, Biyoinformatik; biyobelirteç, MiRNA, Alzheimer’s disease, Hub gen, Bioinformatic; biomarker, Hepatocellular carcinoma, Hub genes
Citation
Pirim, D. ve Yılmaz, E. B. (2020).''Geç başlangıçlı alzheimer hastalığı ve hepatosellüler karsinom ile ilişkili ortak moleküler yolakların ve anahtar biyobelirteçlerin biyoinformatik analizlerle araştırılması''. Uludağ Üniversitesi Tıp Fakültesi Dergisi, 46(2), 161-168.