The Pan-Cancer analysis of pseudogene expression reveals biologically and clinically relevant tumour subtypes

Abstract

Although individual pseudogenes have been implicated in tumor biology, the biomedical significance and clinical relevance of pseudogene expression have not been assessed in a systematic way. Here we generate pseudogene expression profiles in 2,808 patient samples of seven cancer types from The Cancer Genome Atlas RNA-seq data using a newly developed computational pipeline. Supervised analysis reveals a significant number of pseudogenes differentially expressed among established tumor subtypes; and pseudogene expression alone can accurately classify the major histological subtypes of endometrial cancer. Across cancer types, the tumor subtypes revealed by pseudogene expression show extensive and strong concordance with the subtypes defined by other molecular data. Strikingly, in kidney cancer, the pseudogene-expression subtypes not only significantly correlate with patient survival, but also help stratify patients in combination with clinical variables. Our study highlights the potential of pseudogene expression analysis as a new paradigm for investigating cancer mechanisms and discovering prognostic biomarkers.

RETRACTED: The Pseudogene DUXAP8 Promotes Non-small-cell Lung Cancer Cell Proliferation and Invasion by Epigenetically Silencing EGR1 and RHOB

“…21 In addition, the rapid development of bioinformatics has led to the identification of thousands of novel transcribed pseudogenes in human cancers based on the next-generation sequencing data of cancer samples. 22 For example, Han et al 23 developed a computational pipeline and detected $10,000 pseudogenes in seven cancer types using The Cancer Genome Atlas (TCGA) RNA sequencing (RNA-seq) data. Many of these pseudogenes are cancer specific, which suggests that pseudogenes may be subtype and prognostic biomarkers in cancers.…”

Integrated methylome and transcriptome analysis reveals novel regulatory elements in pediatric acute lymphoblastic leukemia

“…24,25 The relationship between differentially expressed pseudogene transcripts and the expression of parent gene targets was diverse in our data (Table S5). In some instances, the upregulation of a pseudogene was associated with the downregulation of its parent gene.…”

DNA methylation markers for diagnosis and prognosis of common cancers

“…Extensive perturbations of DNA methylation have been noted in cancer, causing changes in gene regulation that promote oncogenesis (7)(8)(9). Understanding both epigenetic changes and somatic DNA mutations show promise for improving the characterization of malignancy to predict treatment response and prognosis (3,(10)(11)(12). Some changes in methylation are reproducibly found in nearly all cases of a specific type of cancer.…”

“…Thus, there is a need for strategies to improve diagnostic certainty. Molecular characterization is increasingly used to predict tumor prognosis and response to therapy and offers great potential for improving understanding of an individual patient's tumor (2)(3)(4). Importantly, these methods may have specific utility in scenarios of limited tissue availability or quality.…”