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.

中文翻译：

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ELF4表达与较差的疾病结果和对人类癌症的抗癌药耐药性增加有关

各种转录因子表达的变化助长了肿瘤细胞的恶性表型，其中包括一些经过充分研究的蛋白质，例如p53和Myc。尽管取得了重大进展，但对包括ELF4在内的其他几种转录因子及其如何帮助形成癌细胞中致癌过程的了解却很少。为此，我们进行了生物信息学分析，以帮助详细了解人类癌症中ELF4的转录变异与疾病结局和癌细胞药物反应之间的关系。在这里，我们使用来自9350个样本的癌症基因组图谱癌症计划的ELF4的mRNA转录数据，我们确定了两组患者的肿瘤：在32种不同的人类癌症中表达高ELF4转录本的那些和表达低ELF4转录本的那些。我们发现隔离在这两组中的患者具有不同的临床结局。此外，我们发现，除了与相对较差的疾病结果相关外，表达高ELF4 mRNA转录物的肿瘤往往具有较高的等级，折磨着显着高龄的患者群体，并且具有明显更高的突变负担。通过从癌症药物敏感性基因组学分析612种特征明确的人类癌细胞系对397种抗癌药物的剂量反应曲线，我们发现表达高ELF4 mRNA转录的细胞系对129种抗癌药物的反应性明显降低毒品。我们的分析表明，