RESUMEN
Prostate cancer (PCa) exhibits epidemiological and molecular heterogeneity. Despite extensive studies of its phenotypic and genetic properties in Western populations, its molecular basis is not clear in Chinese patients. To determine critical molecular characteristics and explore correlations between genomic markers and clinical parameters in Chinese populations, we applied an integrative genetic/transcriptomic assay that combines targeted next-generation sequencing and quantitative real-time PCR (qRT-PCR) on samples from 46 Chinese patients with PCa. Lysine (K)-specific methyltransferase 2D (KMT2D), zinc finger homeobox 3 (ZFHX3), A-kinase anchoring protein 9 (AKAP9), and GLI family zinc finger 1 (GLI1) were frequently mutated in our cohort. Moreover, a clinicopathological analysis showed that RB transcriptional corepressor 1 (RB1) deletion was common in patients with a high risk of disease progression. Remarkably, four genomic events, MYC proto-oncogene (MYC) amplification, RB1 deletion, APC regulator of WNT signaling pathway (APC) mutation or deletion, and cyclin-dependent kinase 12 (CDK12) mutation, were correlated with poor disease-free survival. In addition, a close link between KMT2D expression and the androgen receptor (AR) signaling pathway was observed both in our cohort and in The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) data. In summary, our results demonstrate the feasibility and benefits of integrative molecular characterization of PCa samples in disease pathology research and personalized medicine.
RESUMEN
Prostate cancer (PCa) exhibits epidemiological and molecular heterogeneity. Despite extensive studies of its phenotypic and genetic properties in Western populations, its molecular basis is not clear in Chinese patients. To determine critical molecular characteristics and explore correlations between genomic markers and clinical parameters in Chinese populations, we applied an integrative genetic/transcriptomic assay that combines targeted next-generation sequencing and quantitative real-time PCR (qRT-PCR) on samples from 46 Chinese patients with PCa. Lysine (K)-specific methyltransferase 2D (KMT2D), zinc finger homeobox 3 (ZFHX3), A-kinase anchoring protein 9 (AKAP9), and GLI family zinc finger 1 (GLI1) were frequently mutated in our cohort. Moreover, a clinicopathological analysis showed that RB transcriptional corepressor 1 (RB1) deletion was common in patients with a high risk of disease progression. Remarkably, four genomic events, MYC proto-oncogene (MYC) amplification, RB1 deletion, APC regulator of WNT signaling pathway (APC) mutation or deletion, and cyclin-dependent kinase 12 (CDK12) mutation, were correlated with poor disease-free survival. In addition, a close link between KMT2D expression and the androgen receptor (AR) signaling pathway was observed both in our cohort and in The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) data. In summary, our results demonstrate the feasibility and benefits of integrative molecular characterization of PCa samples in disease pathology research and personalized medicine.
Asunto(s)
Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Anclaje a la Quinasa A/genética , Biomarcadores de Tumor/genética , China , Proteínas del Citoesqueleto/genética , Proteínas de Unión al ADN/genética , Amplificación de Genes , Secuenciación de Nucleótidos de Alto Rendimiento , Proteínas de Homeodominio/genética , Mutación , Proteínas de Neoplasias/genética , Neoplasias de la Próstata/patología , Proto-Oncogenes Mas , Receptores Androgénicos/genética , Transducción de Señal/genética , Proteína con Dedos de Zinc GLI1/genéticaRESUMEN
<p><b>OBJECTIVE</b>To analyze the advantages of spatial measurement of anatomical parameters in a 3D model in surgical planning for laparoscopic partial nephrectomy (LPN).</p><p><b>METHODS</b>From February, 2016 to October, 2017, 37 patients diagnosed with T1 renal mass underwent LPN based on 3D reconstruction after enhanced CT scanning using the Uromedix-3D system (group A), and another 38 patients received LPN with conventional CT planning (group B). The anatomical parameters were measured in the reconstructed 3D model and the demographic data, surgical outcome and postoperative data were compared between the two groups.</p><p><b>RESULTS</b>In group A, the average time for 3D model reconstruction was (29.3∓9.7) min; the length, width and depth of the renal defect in 3D model were 3.2∓1.1 cm, 2.6∓0.9 cm and 1.7∓0.7 cm, respectively; The distance of the tumor from the collecting system was 3.8∓2.2 mm; The mean R.E.N.A.L score of the patients was 7∓1.5, and 3 patients had accessory renal artery and 2 had early branching of the renal artery. LPNs were completed via the retroperitoneal approach in all the 75 patients without conversion to open or total nephrectomy. Group A and group B showed significant differences in warm ischemic time (26.7∓6.4 vs 31.9∓7.0 min), tumor-excision time (8.4∓2.6 vs 10.4∓2.8 min), renal defect suture time (18.3∓3.9 vs 21.5∓3.4 min), 24-h volume of retroperitoneal drainage (88.6∓40.2 vs 134.3∓58.3 mL) and 48-h volume of retroperitoneal drainage (127.9∓54.5 vs 198.1∓86.3 mL), but not in the demographic data, operation time, intraoperative blood loss or postoperative hospital stay.</p><p><b>CONCLUSIONS</b>3D reconstruction of the renal masses can be completed efficiently and accurately using this system. Compared with conventional CT-based measurement, 3D spatial measurement of the anatomical structures helps to increase the precision in the performance of LPN and reduce the warm ischemia time.</p>
RESUMEN
<p><b>OBJECTIVE</b>To investigate the effects of silencing ADP-ribosylation factor 6 (Arf6) on the proliferation, migration, and invasion of prostate cancer cell line PC-3 and the possible molecular mechanisms.</p><p><b>METHODS</b>Three Arf6-specific small interfering RNA (siRNA) were transfected into cultured prostate cancer cell line PC-3. Arf6 expression was examined by real-time PCR and Western blotting. MTT assay, wound healing assay, and Transwell migration and invasion assay were used to observe the effect of Arf6 silencing on the proliferation, migration, and invasion ability of PC-3 cells. The levels of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), ERK1/2, p-AKT, AKT and Rac1 were detected by Western blotting.</p><p><b>RESULTS</b>Transfection of siRNA-3 resulted in significantly decreased Arf6 mRNA and protein expression with inhibition rates of (91.88±3.13)% and (86.37±0.57)%, respectively. Arf6 silencing by siRNA-3 markedly suppressed the proliferation, migration and invasion of PC-3 cells and reduced the expression levels of p-ERK1/2 and Rac1.</p><p><b>CONCLUSION</b>Silencing of Arf6 efficiently inhibits the proliferation, migration, and invasion of PC-3 cells in vitro, and the underlying mechanisms may involve the down-regulation of p-ERK1/2 and Rac1.</p>