RESUMO
OBJECTIVE: To investigate the gene expression profile of CSCs and to explore the key pathways and specific molecular signatures involved in the characteristic of CSCs. MATERIALS AND METHODS: CD133+ /CD44+ CSCs and bulk population (non-CSCs) were isolated from DU-145 cells using fluorescence-activated cell sorting (FACS). We used Illumina HumanHT-12 v4 Expression to investigate gene expression profiling of CSCs and non-CSCs. Protein-protein interaction (PPI) network analysis was performed using the STRING database. Biomarkers selected based on gene expression profiling were visually analyzed using immunofluorescence staining method. An image analysis program, ImageJ®, was used for the analysis of fluorescence intensity. RESULTS: In microarray analysis, we found that many ribosomal proteins and translation initiation factors that constitute the mTOR complex were highly expressed. PPI analysis using the 33 genes demonstrated that there was a close interaction between ribosome biogenesis, translation, and mTOR signaling. The fluorescence amount of mTOR and MLST8 were higher in CSCs compared to non-CSCs. CONCLUSIONS: The increase in a number of genes associated with ribosome biogenesis, translation, and mTOR signaling may be important to evaluate prognosis and determine treatment approach for prostate cancer (PCa). A better understanding of the molecular pathways associated with CSCs may be promising to develop targeted therapies to prolong survival in PCa.
Assuntos
Fatores de Iniciação em Eucariotos/genética , Células-Tronco Neoplásicas/metabolismo , Biogênese de Organelas , Neoplasias da Próstata/genética , Ribossomos/genética , Serina-Treonina Quinases TOR/genética , Transcriptoma , Homólogo LST8 da Proteína Associada a mTOR/genética , Antígeno AC133/metabolismo , Linhagem Celular Tumoral , Fatores de Iniciação em Eucariotos/metabolismo , Citometria de Fluxo , Humanos , Receptores de Hialuronatos/metabolismo , Masculino , Neoplasias da Próstata/metabolismo , Mapas de Interação de Proteínas , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Ribossomos/metabolismo , Esferoides Celulares , Serina-Treonina Quinases TOR/metabolismo , Homólogo LST8 da Proteína Associada a mTOR/metabolismoRESUMO
BACKGROUND: Nephron-sparing surgery (NSS) is currently the recommended treatment modality for selected renal tumors. The prognostic significance of positive surgical margin (PSM) and surgical margin width (SMW) after NSS is controversial. AIM: To evaluate the effect of PSM and SMW on cancer-specific survival (CSS) in patients who underwent NSS. MATERIALS AND METHODS: The pathological samples of 142 patients who underwent NSS were reviewed. Patients were divided into two groups with PSM and negative surgical margin (NSM), and after that those with PSM were divided into two groups according to SMW as those with 0.1-2 mm and those >2 mm. CSS was calculated using Kaplan-Meier method. Cox regression analysis was used to adjust the clinicopathologic variables. A P value < 0.05 was considered statistically significant. RESULTS: Local recurrence rate and distant metastasis rate were higher in patients with PSMs than those with NSMs (P = 0.018 and P = 0.039, respectively). However, there was no significant difference between the two groups in terms of CSS. In the group with SMW 0.1-2 mm, the tumor diameter was longer (P = 0.018), enucleation number was higher (P = 0.026), and local recurrence was higher (P = 0.034) than the group with SMW > 2 mm. There was no significant difference between the two groups in terms of CSS. CONCLUSION: In patients who underwent NSS, PSMs and SMWs have a negative effect on local recurrence but have no significant effect on CSS.