Unknown,Transcriptomics,Genomics,Proteomics

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Radiogenomics reveals significant correlation between quantitative texture radiomic features of biparametric MRI and hypoxia related gene expression in men with localised prostate cancer

ABSTRACT: The aim of this study was to perform the multiscale correlation between quantitative texture features phenotype of pre-biopsy biparametric MRI (bpMRI) and targeted sequence-based RNA expression for hypoxia-related genes. Images from pre-biopsy 3T bpMRI scans in clinically localised prostate cancer (PCa) patients of various risk categories (n=15) were used to extract textural features. The genomic landscape of hypoxia-related genes expression was obtained using post-radical prostatectomy tissue for targeted RNA expression profiling using the TempO-sequence method. The nonparametric Games Howell test was used to correlate the differential expression of the three important hypoxia-related genes with 28 radiomic texture features. Following this, cBioportal was accessed and a gene-oriented query was conducted to extract Oncoprint genomic output graph of the selected hypoxia-related genes from The Cancer Genome Atlas (TCGA). Correlation analysis using Pearson's coefficients calculated against each selected gene profile; survival analysis using Kaplan-Meier estimators were carried out. We found the quantitative bpMR imaging textural features, including histogram and grey level co-occurrence matrix (GLCM), correlated with hypoxia related genes (ANGPTL4, VEGFA, and P4HA1) seen on RNA sequencing using TempO-Seq method. Further radiogenomic analysis, including data accessed on cBioportal genomic database, confirmed that overexpressed hypoxia-related genes significantly correlated with a poor survival outcome, with a median survival of 81.11: 133.00 months in those with and without alterations of genes respectively. In summary, radiomic texture features of bpMRI in localised PCa correlate with the expression of hypoxia-related genes expression in prostate cancer. The expression data analysis showed that hypoxia-related genes are associated with poor survival.

INSTRUMENT(S): Illumina HiSeq 2500

ORGANISM(S): Homo sapiens

SUBMITTER: Chidozie Ogbonnaya

PROVIDER: E-MTAB-12593 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Breast cancer is a heterogeneous disease classified into 3 major subtypes based on the presence or absence of molecular markers for oestrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor-2 (Her2) . Hormone receptor-positive BC (ER+, PR+ and Her-2-), accounts for approximately 70% of patients. Patients with ER- BC account for approximately 30 % of all cases and commonly have a worse prognosis than ER+ patients (9). However, a significant proportion of ER- cases have good outcomes and could potentially benefit from a less aggressive therapy. Triple negative breast cancer (TNBC, ER-, PR- and Her-2-) accounts for approximately 15% of breast cancers and has the poorest outcomes. An hypoxic microenvironment is an important intrinsic component of solid tumours that can result in rapid proliferation of cancer cells and is associated with the lack of oxgyen and abnormal tumour blood vessels. Hypoxia stimulates the hypoxia inducible factor-1α (HIF-1α) that transactivates genes associated with angiogenesis, tumour growth, metastasis, metabolic reprogramming, and treatment resistance. HIF-1α is recognised to induce the expression of carbonic anhydrase IX (CAIX), an enzyme that has been attributed a central role in pH regulation and cancer progression and is particularly pronounced in peri necrotic tumour areas, high-grade BCs. The adaption to hypoxia is governed by multiple transcriptional and post-transcriptional changes in gene expression. Up to 1.5 % of the human genome is estimated to be transcriptionally responsive to hypoxia. Genes and pathways which have been identified as being responsive to hypoxia may have the potential to be used as prognostic or predictive markers, and furthermore, can help identify novel therapeutic targets. The aim of the present study was to gain a better understanding of the transcriptomic and protein pathways associated with CAIX in ER- BC to identify potential therapeutic targets against this aggressive phenotype.

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Radiogenomics reveals significant correlation between quantitative texture radiomic features of biparametric MRI and hypoxia related gene expression in men with localised prostate cancer

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