Genes involved in prostate cancer progression determine MRI visibility

Abstract

MRI is used to image prostate cancer and target tumors for biopsy or therapeutic ablation. The objective was to understand the biology of tumors not visible on MRI that may go undiagnosed and untreated.Methods: Prostate cancers visible or invisible on multiparametric MRI were macrodissected and examined by RNAseq. Differentially expressed genes (DEGs) based on MRI visibility status were cross-referenced with publicly available gene expression databases to identify genes associated with disease progression. Genes with potential roles in determining MRI visibility and disease progression were knocked down in murine prostate cancer xenografts, and imaged by MRI.Results: RNAseq identified 1,654 DEGs based on MRI visibility status. Comparison of DEGs based on MRI visibility and tumor characteristics revealed that Gleason score (dissimilarity test, p<0.0001) and tumor size (dissimilarity test, p<0.039) did not completely determine MRI visibility. Genes in previously reported prognostic signatures significantly correlated with MRI visibility suggesting that MRI visibility was prognostic. Cross-referencing DEGs with external datasets identified four genes (PHYHD1, CENPF, ALDH2, GDF15) that predict MRI visibility, progression free survival and metastatic deposits. Genetic modification of a human prostate cancer cell line to induce miR-101 and suppress CENPF decreased cell migration and invasion. As prostate cancer xenografts in mice, these cells had decreased visibility on diffusion weighted MRI and decreased perfusion, which correlated with immunostaining showing decreased cell density and proliferation.Conclusions: Genes involved in prostate cancer prognosis and metastasis determine MRI visibility, indicating that MRI visibility has prognostic significance. MRI visibility was associated with genetic features linked to poor prognosis.

Centromere protein F and Forkhead box M1 correlation with prognosis of non‑small cell lung cancer

“…Centromere protein F (CENPF), a transient kinetochore protein, exhibits a cell-cycle dependent localization, and is completely degraded at the end of cell division (4)(5)(6). Evidence has shown that CENPF is overexpressed in head and neck squamous cell carcinomas, hepatocellular carcinoma, breast cancer and prostate cancer, and it may be a prognostic marker for these cancers (7)(8)(9)(10)(11)(12). Forkhead box M1 (FOXM1) is a typical proliferation-associated factor and plays an important role in development (13)(14)(15)(16)(17)(18).…”

Centromere protein F (CENPF), a microtubule binding protein, modulates cancer metabolism by regulating pyruvate kinase M2 phosphorylation signaling

“…As a regulator of chromosome segregation, CENPF is expressed in a cell cycle-dependent manner; it gradually accumulates during the cell cycle, reaches peak levels in the G 2 /M phase, and then degrades upon completion of mitosis [16]. CENPF is upregulated in PC and plays an important part in malignant progression [17,18]. Interestingly, CENPF also significantly enhances chemotherapeutic sensitivity [19].…”

Downregulation of CENPF Remodels Prostate Cancer Cells and Alters Cellular Metabolism

“…This comprehensive analysis provides a valuable opportunity to better understand the biochemical changes underlying cancer metabolism and improve early detection, progression, and therapeutic monitoring . Metabolomics can also respond to clinical challenges by providing a method of detecting vital and promising novel biomarkers . In terms of cancer, metabolomics can enable additional measurement of downstream activities, thereby allowing for the discovery of key oncometabolites .…”