Publication: Network-based integration of multi-omic profiles to purpose new biomarker candidates in pancreatic cancer
Abstract
Pankreas duktal adenokansinoma (PDAC), geç tanı, kötü sağkalım oranları ve yüksek metastaz insidansı ile en ölümcül malignitelerden biridir. Moleküler mekanizmasındaki belirsizlikler göz önüne alındığında, bu çalışmada, ağ tabanlı bütünleştirici analiz ile PDAC için potansiyel biyobelirteçleri belirlemek için circRNA'ların PDAC ilerlemesindeki moleküler düzenleyici imzalarına daha fazla ışık tutmayı ve farklı bir bakış açısı sağlamayı amaçladık. PDAC'nin mRNA, miRNA ve circRNA ifade profillerinin incelenmesi amacıyla dokuz adet Gene Expression Omnibus mikroarray veri seti indirildi. Anlatımı anlamlı bir şekilde değişen mRNA'lar (DEG’ler), miRNA'lar (DEmiRNA'lar) ve circRNA'lar (DEcircRNA'lar), mikrodizi veri setlerinin istatistiksel olarak analiz edilmesiyle tanımlandı. Rekabetçi endojen RNA (ceRNA; DEG-DEmiRNA-DEcircRNA) düzenleyici ağı, circRNA-miRNA çiftlerinin miRNA-mRNA çiftleriyle birleştirilmesiyle oluşturulmuştur. Yolak ve fonksiyonel zenginleştirme analizi, Metascape kullanılarak yapıldı ve MCODE eklentisi kullanılarak hub genleri tanımlandı. Toplam 110 DEcircRNa, 10 DEmiRNa ve 248 DEG tanımlandı. PDAC'ye özgü 46 circRNA, 10 miRNA ve 31 mRNA içeren ceRNA ağı kuruldu. Protein-protein etkileşim ağı ve modül analizi, ceRNA ağında yedi hub geni (SUZ12, IGF2BP2, PPP1CB, FN1, ACTN4, TP53 ve PRKAA1) tanımladı. DEG'lerin ceRNA düzenleyici ağdaki işlevsel açıklaması, bu DEG'lerin hücre gelişimi, PI3K-AKT sinyal yolu ve onkojenik MAPK sinyalinin düzenlenmesinde önemli ölçüde zenginleştiğini gösterdi. Sonuç olarak, bu araştırma, PDAC karsinojenezinin düzenlenmesinde ceRNA düzenleyici mekanizmaların mevcut anlayışını geliştirmekte ve aday biyobelirteçler olarak yeni circRNA'lar sağlamaktadır.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies related to late diagnosis, poor survival rates, and high incidence of metastasis. Considering the uncertainties in its molecular mechanism, in the present study, we aimed to provide shed more light into the molecular regulatory signatures of circRNAs in PDAC progression and a different perspective in order to identify potential biomarkers for PDAC by network-based integrative analysis. The mRNA, miRNA, and circRNA expression profiles of PDAC were downloaded nine Gene Expression Omnibus microarray datasets. The differentially expressed mRNAs (DEGs), miRNAs (DEmiRNAs), and circRNAs (DEcircRNAs) were identified by statistically analysing the microarray datasets. The competing endogenous RNA (ceRNA; DEG-DEmiRNA-DEcircRNA) regulatory network was constructed by combining circRNA-miRNA pairs with miRNA-mRNA pairs. The pathway and functional enrichment analysis were carried out using the Metascape, and hub genes were identified using the MCODE plugin. A total of 110 DEcircRNAs, 10 DEmiRNAs, and 248 DEGs were identified. The ceRNA network including 46 circRNAs, 10 miRNAs, and 31 mRNAs specific to PDAC was established. The protein-protein interaction network and module analysis identified seven hubgenes (SUZ12, IGF2BP2, PPP1CB, FN1, ACTN4, TP53, and PRKAA1) in ceRNA network. The functional annotation of DEGs in the ceRNA regulatory network showed that these DEGs were significantly enriched in the regulation of cell development, the PI3K-AKT signaling pathway, and oncogenic MAPK signaling. In conclusion, this research improve current understanding of the ceRNA regulatory mechanisms in the regulation of PDAC carcinogenesis and provide novel circRNAs as candidate biomarkers.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies related to late diagnosis, poor survival rates, and high incidence of metastasis. Considering the uncertainties in its molecular mechanism, in the present study, we aimed to provide shed more light into the molecular regulatory signatures of circRNAs in PDAC progression and a different perspective in order to identify potential biomarkers for PDAC by network-based integrative analysis. The mRNA, miRNA, and circRNA expression profiles of PDAC were downloaded nine Gene Expression Omnibus microarray datasets. The differentially expressed mRNAs (DEGs), miRNAs (DEmiRNAs), and circRNAs (DEcircRNAs) were identified by statistically analysing the microarray datasets. The competing endogenous RNA (ceRNA; DEG-DEmiRNA-DEcircRNA) regulatory network was constructed by combining circRNA-miRNA pairs with miRNA-mRNA pairs. The pathway and functional enrichment analysis were carried out using the Metascape, and hub genes were identified using the MCODE plugin. A total of 110 DEcircRNAs, 10 DEmiRNAs, and 248 DEGs were identified. The ceRNA network including 46 circRNAs, 10 miRNAs, and 31 mRNAs specific to PDAC was established. The protein-protein interaction network and module analysis identified seven hubgenes (SUZ12, IGF2BP2, PPP1CB, FN1, ACTN4, TP53, and PRKAA1) in ceRNA network. The functional annotation of DEGs in the ceRNA regulatory network showed that these DEGs were significantly enriched in the regulation of cell development, the PI3K-AKT signaling pathway, and oncogenic MAPK signaling. In conclusion, this research improve current understanding of the ceRNA regulatory mechanisms in the regulation of PDAC carcinogenesis and provide novel circRNAs as candidate biomarkers.