Common Biological Pathways Triggered by Different Genes in Cholangiocarcinoma and Hepatocellular Carcinoma Patients

Öz

Cholangiocarcinoma (CHOL) is a highly lethal type of cancer that is difficult to diagnose early. There are limitations in radiological imaging in the diagnosis of CHOL, and it becomes necessary to determine genetic-based and specific biomarkers other than invasive diagnostic methods such as biopsy diagnosis. Unlike the studies in the literature that carried out these purposes, in our study, the genes that were commonly upregulated in intrahepatic (iCHOL) and extrahepatic (eCHOL) cholangiocarcinoma patients were determined. In addition, our study aimed to identify genes that are upregulated in CHOL patients, differently from hepatocellular carcinoma (LICH), and in common with LIHC patients, since it is difficult to differentiate CHOL cancers from LIHC cancers in the clinic. Gene expression data of the patients were provided from the NCBI Gene Expression Omnibus (GEO) database (GSE121248, GSE132305 and GSE45001). In the study, upregulated genes (differentially expressed genes-DEGs) were detected between cancerous and non-cancerous samples using the linear modeling method in the R LIMMA package. Gene set enrichment analysis (Functional enrichment analysis) (GSEA) was performed using ShinyGO 0.80 webtool to determine which biological pathways the detected genes affect. According to our results, we focused on 4 genes (F2R, ITGA11, LAMC2 and LAMB3) that were upregulated in CHOL patients differently than in LIHC patients. Two commonly upregulated genes (COL1A1, ITGA2) were detected in CHOL and LIHC patients. The biological pathways that the genes in question commonly indicate are the PI3K-Akt signaling pathway and extracellular matrix (ECM)-receptor interaction processes. The identified genes and the results of protein-protein and drug interaction studies will be supported by clinical trials and can be effectively targeted to differentiate CHOL and LIHC cancers.

Anahtar Kelimeler

• cholangiocarcinoma
• intrahepatic
• extrahepatic
• hepatocellular carcinoma
• biomarker

Kolanjiyokarsinom ve Hepatoselüler Karsinom Hastalarında Farklı Genler Tarafından Tetiklenen Ortak Biyolojik Yolaklar

Öz

Kolanjiyokarsinom (CHOL) erken teşhis edilmesi zor olan ve oldukça yüksek düzeyde öldürücü bir kanser türüdür. CHOL tanısında radyolojik görüntülemede kısıtlılıklar mevcuttur ve biyopsi ile tanı yöntemi gibi invaziv tanı yöntemleri dışında genetik tabanlı ve özgün biyobelirteçlerin belirlenmesi zorunlu hale gelmektedir. Literatürde bu amaçlar gerçekleştirilen çalışmalar çalışmalardan farklı olarak bizim çalışmamızda öncelikle intrahepatik (iCHOL) ve ekstrahepatik (eCHOL) kolanjiyokarsinom hastalarında ortak upregüle olan genler belirlenmiştir. Ayrıca çalışmamızda klinikte CHOL kanserlerinin LIHC kanserinden ayırt edici tanısının zor olması sebebiyle CHOL hastalarında hepatoselüler karsinomdan (LICH) farklı olarak ve LIHC hastaları ile ortak olarak upregüle edilen genlerin tespit edilmesi de amaçlanmıştır. Hastaların gen yoğunluk verileri NCBI Gene Expression Omnibus (GEO) veri tabanından (GSE121248, GSE132305 ve GSE45001) sağlanmıştır. Çalışmada R LIMMA paketinde yer alan lineer modelleme yöntemi kullanılarak kanserli olan ve olmayan örnekler arasında upregüle genler (differentially expressed genes-DEGs) tespit edilmiştir. Tespit edilen genlerin hangi biyolojik yolaklara etki ettiğini belirlemek için Gen seti zenginleştirme analizi (Fonksiyonel zenginleştirme analizi) (GSEA) ShinyGO 0.80 webtool kullanılarak yapılmıştır. Sonuçlarımıza göre CHOL hastalarında LIHC hastalarından farklı olarak upregüle edilen 4 gene (F2R, ITGA11, LAMC2 ve LAMB3) odaklanılmıştır. CHOL ve LIHC hastalarında ise ortak olarak upregüle edilen 2 gen (COL1A1, ITGA2) tespit edilmiştir. Söz konusu genlerinin ortak olarak işaret ettiği biyolojik yolaklar PI3K-Akt sinyal yolağı ve ekstraselüler matriks (ECM)-reseptör etkileşimi süreçleridir. Belirlenen genler ile protein-protein ve ilaç etkileşim çalışmaları sonuçları klinik denemeler ile desteklenip CHOL ile LIHC kanserlerinin ayırt edilmesinde etkin bir şekilde hedeflenebilecektir.

Anahtar Kelimeler

• kolanjiyokarsinom
• intrahepatik
• ekstrahepatik
• hepatoselüler karsinom
• biyobelirteç

Kaynakça

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