RESUMEN
Sunitinib resistance is, nowadays, the major challenge for advanced renal cell carcinoma patients. Illuminating the potential mechanisms and exploring effective strategies to overcome sunitinib resistance are highly desired. We constructed a reliable gene signature which may function as biomarkers for prediction of sunitinib sensitivity and clinical prognosis. The gene expression profiles were obtained from The Cancer Genome Atlas database. By performing GEO2R analysis, numerous differentially expressed genes (DEGs) were found to be associated with sunitinib resistance. To acquire more precise DEGs, we integrated three different microarray datasets. Functional analysis revealed that these DEGs were mainly involved in Rap1 signaling pathway, p53 signaling pathway and Ras signaling pathway. Then, top five hub genes, BIRC5, CD44, MUC1, TF, CCL5, were identified from protein-protein interaction (PPI) network. Sub-network analysis carried out by MCODE plugin revealed that key DEGs were related with PI3K-Akt signaling pathway, Rap1 signaling pathway and VEGF signaling pathway. Next, we established sunitinib-resistant OS-RC-2 and 786-O cell lines and validated the expression of five hub genes in cell lines. To further evaluate the potentials of five-gene signature for predicting clinical prognosis, we analyzed RCC patients with gene expressions and overall survival information from two independent patient datasets. The Kaplan-Meier estimated the OS of RCC patients in the low- and high-risk groups according to gene expression signature. Multivariate Cox regression analysis indicated that the prognostic power of five-gene signature was independent of clinical features. In conclusion, we developed a five-gene signature which can predict sunitinib sensitivity and OS for advanced RCC patients, providing novel insights into understanding of sunitinib-resistant mechanisms and identification of RCC patients with poor prognosis.
Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma de Células Renales/tratamiento farmacológico , Resistencia a Antineoplásicos/genética , Sunitinib/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Carbohidratos Asociados a Tumores/genética , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Quimiocina CCL5/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Receptores de Hialuranos/genética , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Mucina-1/genética , Pronóstico , Sunitinib/efectos adversos , Survivin/genética , Transcriptoma/genéticaRESUMEN
AIM: To explore the feasibility and safety of laparoscopic colonic anastomosis using a degradable stent in a porcine model. METHODS: Twenty Bama mini-pigs were randomly assigned to a stent group (n = 10) and control group (hand-sewn anastomosis, n = 10). The anastomotic completion and operation times were recorded, along with histological examination, postoperative general condition, complications, mortality, bursting pressure, and the average anastomotic circumference (AC). RESULTS: All pigs survived postoperatively except for one in the stent group that died from ileus at 11 wk postoperatively. The operation and anastomotic completion times of the stent group were significantly shorter than those of the control group (P = 0.004 and P = 0.001, respectively). There were no significant differences in bursting pressure between the groups (P = 0.751). No obvious difference was found between the AC and normal circumference in the stent group, but AC was significantly less than normal circumference in the control group (P = 0.047, P < 0.05). No intestinal leakage and luminal stenosis occurred in the stent group. Histological examination revealed that the stent group presented with lower general inflammation and better healing. CONCLUSION: Laparoscopic colonic anastomosis with a degradable stent is a simple, rapid, and safe procedure in this porcine model.
