ELF4 Expression is Associated with Worse Disease Outcomes and Increased Resistance to Anticancer Agents in Human Cancers

Résumé

The malignant phenotype of tumour cells is fuelled by changes in the expression of various transcription factors, which include some of the well-studied proteins such as p53 and Myc. Despite significant progress made, little is known about several other transcription factors, including ELF4, and how they help shape the oncogenic processes that occur in cancer cells. To this end, we performed a bioinformatics analysis to facilitate a detailed understanding of how the transcriptional variations of ELF4 in human cancers are related to disease outcomes and the cancer cell drug responses. Here, using mRNA transcription data of ELF4 from the Cancer Genome Atlas pan-cancer project of 9,350 samples, we identify two groups of patient's tumours: those that expressed high ELF4 transcripts and those that expressed low ELF4 transcripts across 32 different human cancers. We uncover that patients segregated into these two groups are associated with different clinical outcomes. Further, we found that, besides being associated with comparatively worse disease outcomes, tumours that express high ELF4 mRNA transcript tend to be of a higher-grade, afflict a significantly older patient population and have a significantly higher mutation burden. By analysing dose-response profiles to 397 anti-cancer drugs of 612 well-characterised human cancer cell lines from the Genomics of Drug Sensitivity in Cancer, we discover that cell lines that express high ELF4 mRNA transcript are significantly less responsive to 129 anti-cancer drugs. Collectively our analyses have shown that, across the 32 different human cancers, the patients afflicted with tumours that overexpress ELF4 tended to have a more aggressive disease that is also is more likely more refractory to most anti-cancer drugs, a finding upon which we could devise novel categorisation of patient tumours, treatment and prognostic strategies.

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