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Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
A pan-cancer analysis of the oncogenic role of ERCC6L
Zhimin Lu1, Lihong Fei2, Guoxin Hou3
1Department of Outpatient, The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China.
Background:
Excision repair cross-complementation group 6 like (ERCC6L), a polo-like kinase 1 (PLK1)-interacting checkpoint helicase, confers a high risk of cancer and enhances the progression of a variety of cancers. The present investigation aimed to elucidate the pan-cancer expression patterns of ERCC6L and to examine the possibility of using this gene for patient diagnosis and prognosis.
Methods:
The expression patterns of ERCC6L in normal and cancer patients at various clinical stages were explored based on TCGA datasets. Subsequently, Bioinformatics techniques were then used to analyze patient's survival probabilities, Cox multivariate clinical parameters, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms related to ERCC6L, the correlation between mRNA expression levels and patient survival, genetic alterations or somatic mutations of ERCC6L, and immune infiltration.
Results:
Most cancer types had higher ERCC6L mRNA levels than normal tissue. Higher ERCC6L expression levels were correlated with poor prognosis for cancer patients. Thus, ERCC6L may serve as an effective diagnostic and prognostic marker for multiple cancers. Moreover, ERCC6L expression levels were higher in patients with higher clinical tumor grades and were associated with poor prognoses at these stages. GO and KEGG analyses revealed a correlation between ERCC6L expression levels and chromatin and cell cycle events. We also found that the mRNA expression level of the ERCC6L promoter and a favorable prognosis was negatively correlated with the promoter's methylation but not with copy number variation. A quantitative analysis of immune infiltration suggested a positive correlation between ERCC6L levels and the infiltration of Th2 immune cells in main cancer types. Finally, we examined the ERCC6L somatic mutations, especially single-nucleotide variants, and ERCC6L expression-related drug sensitivity.
Conclusions:
Herein, we reported a comprehensive investigation of the tumor-promoting role of ERCC6L in various cancer types. ERCC6L is a candidate biomarker for diagnosing and unfavorable prognosis of specific cancers.
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