Abstract
Currently, seven molecular subtypes of prostate cancer (PCa) are known, the most common of which being the subtype characterized by the presence of the TMPRSS2–ERG fusion transcript. While there is a considerable amount of work devoted to the influence of this transcript on the prognosis of the disease, data on its role in the progression and prognosis of PCa remain controversial. The present study is devoted to the analysis of the association between the TMPRSS2–ERG transcript and the biochemical recurrence of PCa. The study included two cohorts: the RNA–Seq sample of Russian patients with PCa (n = 72) and the TCGA–PRAD data (n = 203). The results of the analysis of the association between the TMPRSS2–ERG transcript and biochemical recurrence were contradictory. The differential expression analysis (biochemical recurrence cases versus biochemical recurrence-free) and the gene set enrichment analysis revealed a list of genes involved in major cellular pathways. The GNL3, QSOX2, SSPO, and SYS1 genes were selected as predictors of the potential prognostic model (AUC = 1.000 for a cohort of Russian patients with PCa and AUC = 0.779 for a TCGA–PRAD cohort).
Highlights
Seven major molecular subtypes of prostate cancer (PCa), identified by the Cancer Genome Atlas Research Network, TCGA–PRAD project [1], are known
We studied the association between the presence and expression level of the TMPRSS2–ERG fusion transcript and Biochemical recurrence (BCR) using a cohort of 72 PCa samples obtained from Russian patients
Using Quantitative PCR (qPCR), we assessed the expression of TMPRSS2–ERG transcript in 72 tumor samples of PCa and in paired adjacent normal tissues obtained from Russian patients
Summary
Seven major molecular subtypes of prostate cancer (PCa), identified by the Cancer Genome Atlas Research Network, TCGA–PRAD project [1], are known. Four of the seven subtypes are characterized by the presence of fusion transcripts between the TMPRSS2 exons and the exons of genes encoding members of the erythroblast transformationspecific (ETS) family of transcription factors: ERG, ETV1, ETV4, and FLI1 (the frequency of the subtypes is 46%, 8%, 4%, and 1%, respectively). About half of all PCa cases have a TMPRSS2–ERG fusion transcript, which is formed due to an intrachromosomal rearrangement leading to the fusion of two genes: TMPRSS2 and ERG. The TMPRSS2 gene is characterized by a higher expression level compared with that of ERG gene expression in the prostate tissue [3]; their fusion leads to a 4.0/). Multiple increases in the expression of the ERG entail serious transcriptomic reprogramming and altered cell signaling (for example, activation of WNT/TGF-beta and NOTCH pathways).
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