Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Puchas, P.
Expression Analysis of Eukaryotic Translation Initiation Factors in Pancreatic Ductal Adenocarcinoma
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2019. pp. 100
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Golob-Schwarzl Nicole
- Haybäck Johannes
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- Abstract:
- Introduction: Pancreatic cancer is one of the major causes of cancer related death worldwide. Its most important subtype is pancreatic ductal adenocarcinoma (PDAC). Deregulation of protein synthesis has been observed in various malignancies. Translation initiation is the rate-limiting step of protein synthesis which is regulated by eukaryotic translation initiation factors (eIFs). Differential expression of various eIFs has recently been reported in a range of malignancies. However, knowledge concerning eIF expression in PDAC remains scarce. The aim of this work was to provide insights into eIF expression patterns in PDAC and to analyze potential usefulness of eIFs as prognostic biomarkers. Methods: Immunohistochemistry (IHC) was used to characterize eIF expression in 174 cases of PDAC compared to 9 non-neoplastic pancreatic tissues (NNTs). In vitro expression analysis was performed on protein level using Immunoblots for PDAC (n = 56) and NNT (n = 28) and on mRNA level using qRT-PCR for PDAC (n = 38) and NNT (n = 22). Survival analysis was performed with protein expression data and in silico with The Cancer Genome Atlas (TCGA) public dataset (n = 125). Results: PDAC samples showed differential expression of various eIF subunits such as downregulation of eIF1, eIF2alpha, eIF3C and eIF6 and upregulation of eIF3A in IHC. Immunoblot analysis confirmed the downregulation of eIF1, eIF2alpha, eIF3C and eIF6 and further showed downregulation of eIF1A, phosphorylated eIF2alpha (p-eIF2alpha), eIF3B and eIF4E. mRNA levels of EIF1 and EIF1AX were found at lower levels in PDAC samples. High eIF2alpha protein level correlated with worse outcome. Additionally, high EIF2A and EIF3C mRNA levels correlated with poor prognosis, whereas high EIF1 mRNA predicted better outcome. Conclusion: In this work, alterations in the expression of various eIFs in PDAC were demonstrated on protein and mRNA level, indicating their importance for pancreatic tumorigenesis. Additionally, their relevance for tumor biology is supported by the findings, that EIF1, EIF2A and EIF3C mRNA as well as eIF2alpha protein levels significantly correlated with patient overall survival. They might therefore serve as prognostic biomarkers. However, further investigation is needed to fully understand the molecular mechanisms and implications of eIFs in PDAC tumorigenesis.