Abstract
Eukaryotic translation factors, especially initiation factors have garnered much attention with regards to their role in the onset and progression of different cancers. However, the expression levels and prognostic significance of translation elongation factors remain poorly explored in different cancers. In this study, we have investigated the mRNA transcript levels of seven translation elongation factors in different cancer types using Oncomine and TCGA databases. Furthermore, we have identified the prognostic significance of these factors using Kaplan-Meier Plotter and SurvExpress databases. We observed altered expression levels of all the elongation factors in different cancers. Higher expression of EEF1A2, EEF1B2, EEF1G, EEF1D, EEF1E1 and EEF2 was observed in most of the cancer types, whereas reverse trend was observed for EEF1A1. Overexpression of many factors predicted poor prognosis in breast (EEF1D, EEF1E1, EEF2) and lung cancer (EEF1A2, EEF1B2, EEF1G, EEF1E1). However, we didn’t see any common correlation of expression levels of elongation factors with survival outcomes across cancer types. Cancer subtype stratification showed association of survival outcomes and expression levels of elongation factors in specific sub-types of breast, lung and gastric cancer. Most interestingly, we observed a reciprocal relationship between the expression levels of the two EEF1A isoforms viz. EEF1A1 and EEF1A2, in most of the cancer types. Our results suggest that translation elongation factors can have a role in tumorigenesis and affect survival in cancer specific manner. Elongation factors have potential to serve as biomarkers and therapeutic drug targets, yet further study is required. Reciprocal relationship of differential expression between EEF1A isoforms observed in multiple cancer types indicates opposing roles in cancer and needs further investigation.
Highlights
Cancer is a multifactorial disease wherein the expression levels of many genes, of those regulating growth and division of cells, are altered [1]
As we observed significant changes in the expression of all elongation factors, further we looked for differential expression in specific cancer types and their subtypes
The analysis revealed that higher expression of EEF1A1 was significantly associated with relapse free survival (RFS) and distant metastasis free survival (DMFS), but not with overall survival (OS) or post progression survival (PPS), in breast cancer
Summary
Cancer is a multifactorial disease wherein the expression levels of many genes, of those regulating growth and division of cells, are altered [1]. The expression and functionality of these genes is regulated at multiple levels viz. Much attention has been given to unravel the regulation of gene expression at the level of translation, with regards to controlling the process of carcinogenesis [1]. EEF2 was identified as a tumor associated antigen overexpressed in the majority of several types of cancers and plays an oncogenic role in cancer cell growth [29]. These preliminary studies suggest that in addition to EEF1A2, other translation elongation factors are involved in multiple human cancers
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