HBV ilişkili hepatoselüler karsinomlarda aurora kinaz a'nin rolümoleküler ve immünohistokimyasal çalışma
Küçük Resim Yok
Tarih
2023
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
İnönü Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Başlıca risk faktörleri arasında Hepatit B virüs'ün (HBV) sayıldığı Hepatoselüler karsinom (HCC), en ölümcül kanserlerden biridir. Kriptojenik Hepatoselüler karsinom (KR-HCC), klinik ve serolojik olarak bir etyoloji ile ilişkilendirilmeyen HCC'yi ifade eder. Aurora Kinaz A (AURKA) geni birçok kanser türünde aşırı eksprese edilir. Çalışmamızla, HBV ilişkili HCC (HBV-HCC) ve KR-HCC olgularında, AURKA gen amplifikasyonu ve ifade düzeyi yanısıra AURKA'nın, substratları olan P53Ser315, PLK-1Thr210 ve BRCA1 de etkinliği araştırıldı. Materyal ve Metot: Çalışma, her gurubun 17 olguyla temsil edildiği; HBV-HCC (Grup I), KR-HCC (Grup II) ve Kontrol grubu (normal karaciğer dokusu) (Grup III) olarak tasarlandı. Çalışmada, moleküler yöntemlerle, AURKA gen kopya sayısı değişikliği (gen-KSD) ve ekspresyon düzeyi incelendi. Ayrıca immünohistokimyasal yöntemle (İHK) AURKA'nın, substratları P53Ser315, PLK-1Thr210 ve BRCA1 üzerinden etkinliği araştırıldı. Bulgular: Grup I ve Grup II, Kontrol gurubuyla (Grup III) karşılaştırıldığında gen-KSD açısından anlamlı bir fark bulunmadı (p=0.060). AURKA düzeyi Grup I-Grup II de yüksek olup Grup III'le aralarındaki fark anlamlıydı (p<0.001). P53 Ser315 her iki HCC grubunda (p<0.001), PLK-1Thr210 Grup II'de (p=0.001), BRCA1 ise Grup I'de (p=0.006) yüksekti ve kontrol grubuyla farklılık istatistiksel olarak anlamlıydı. Sonuç: HBV-HCC ve KR-HCC olgularında AURKA'nın aşırı ifade edildiğin görüldü. AURKA aracılı fosforilasyonla etkinliği artan PLK-1 KR-HCC olgularında, BRCA1 ise HBV-HCC olgularında yüksek oranda ifade edildiği saptandı. Sonuçlar, AURKA ile etkin olduğu BRCA1 ve PLK-1'in inhibisyon hedefli tedavilerde HBV-HCC ve KR-HCC için farklı yaklaşım ve strateji geliştirilmesinin önemini ortaya koydu. Anahtar Kelimeler: Aurora Kinaz A, PLK-1, Hepatoselüler karsinom, HBV ilişkili HCC, Kriptojenik HCC
Aim: Hepatocellular carcinoma (HCC) is one of the deadliest cancers, with Hepatitis B Virus (HBV) among its major risk factors. Cryptogenic hepatocellular carcinoma (KR-HCC) refers to HCC that is clinically and serologically unrelated to an etiology. The Aurora Kinase A (AURKA) gene is overexpressed in many types of cancer. In our study, in HBV-associated HCC (HBV-HCC) and CR-HCC cases, AURKA gene amplification and expression level, as well as the efficiency of AURKA, its substrates P53Ser315, PLK-1Thr210 and BRCA1 were investigated. Material and Method: In the study, each group was represented by 17 cases; It was designed as HBV-HCC (Group I), KR-HCC (Group II) and Control group (normal liver tissue) (Group III). In the study, AURKA gene copy number change (gene-KSD) and expression level were examined by molecular methods. In addition, the effectiveness of AURKA on its substrates P53Ser315, PLK-1Thr210 and BRCA1 was investigated by immunohistochemical method (IHC). Results: When Group I and Group II were compared with the Control group (Group III), no significant difference was found in terms of gene-KSD (p=0.060). AURKA level was high in Group I-Group II and the difference between Group III was significant (p<0.001). P53 Ser315 was higher in both HCC groups (p<0.001), PLK-1Thr210 was higher in Group II (p=0.001), BRCA1 was higher in Group I (p=0.006), and the difference between the control group and them was statistically significant. Conclusion: Overexpression of AURKA was observed in HBV-HCC and CR-HCC cases. PLK-1, whose activity was increased by AURKA-mediated phosphorylation, was found to be highly expressed in CR-HCC cases, and BRCA1 in HBV-HCC cases. The results demonstrated the importance of developing different approaches and strategies for HBV-HCC and KR-HCC in therapies targeting the inhibition of substrates BRCA1 and PLK-1 with AURKA. Keywords: Aurora Kinase A, PLK-1, Hepatocellular carcinoma, HBV-related HCC, Cryptogenic HCC
Aim: Hepatocellular carcinoma (HCC) is one of the deadliest cancers, with Hepatitis B Virus (HBV) among its major risk factors. Cryptogenic hepatocellular carcinoma (KR-HCC) refers to HCC that is clinically and serologically unrelated to an etiology. The Aurora Kinase A (AURKA) gene is overexpressed in many types of cancer. In our study, in HBV-associated HCC (HBV-HCC) and CR-HCC cases, AURKA gene amplification and expression level, as well as the efficiency of AURKA, its substrates P53Ser315, PLK-1Thr210 and BRCA1 were investigated. Material and Method: In the study, each group was represented by 17 cases; It was designed as HBV-HCC (Group I), KR-HCC (Group II) and Control group (normal liver tissue) (Group III). In the study, AURKA gene copy number change (gene-KSD) and expression level were examined by molecular methods. In addition, the effectiveness of AURKA on its substrates P53Ser315, PLK-1Thr210 and BRCA1 was investigated by immunohistochemical method (IHC). Results: When Group I and Group II were compared with the Control group (Group III), no significant difference was found in terms of gene-KSD (p=0.060). AURKA level was high in Group I-Group II and the difference between Group III was significant (p<0.001). P53 Ser315 was higher in both HCC groups (p<0.001), PLK-1Thr210 was higher in Group II (p=0.001), BRCA1 was higher in Group I (p=0.006), and the difference between the control group and them was statistically significant. Conclusion: Overexpression of AURKA was observed in HBV-HCC and CR-HCC cases. PLK-1, whose activity was increased by AURKA-mediated phosphorylation, was found to be highly expressed in CR-HCC cases, and BRCA1 in HBV-HCC cases. The results demonstrated the importance of developing different approaches and strategies for HBV-HCC and KR-HCC in therapies targeting the inhibition of substrates BRCA1 and PLK-1 with AURKA. Keywords: Aurora Kinase A, PLK-1, Hepatocellular carcinoma, HBV-related HCC, Cryptogenic HCC
Açıklama
Anahtar Kelimeler
Moleküler Tıp, Molecular Medicine, Onkoloji
