Clinical significance of expression level of CX3CL1–CX3CR1 axis in bone metastasis of lung cancer

Purpose To investigate the clinical significance of CX3 chemokine ligand 1(CX3CL1) and CX3CR1 in patients with bone metastasis from lung cancer. The expression levels of CX3CL1 and CX3CR1 mRNA and protein in primary lung cancer and lung cancer bone metastasis were detected by qRT-PCR and Western blot. Methods One hundred patients with lung cancer were divided into a boneless metastasis group (50 patients with bone metastasis) and a bone metastasis group (50 patients without distant metastasis). The bone transfer component was graded by Soloway classification (0 to III). The expression levels of serum CX3CL1–CX3CR1 axis were detected by enzyme-linked immunosorbent assay (ELISA). RT-qPCR and Western Blot were used to verify the transfection efficiency. The scratching assay was used to detect the migration of CX3CL1 to 95-D cells after down-regulating the expression of CX3CR1. Results The expression levels of CX3CL1 and CX3CR1 mRNA and protein in the primary lung cancer and lung cancer bone metastasis were significantly higher than those in the adjacent tissues (P < 0.0001). The levels of serum CX3CL1 and CX3CR1 in bone metastasis group were significantly higher than those in boneless metastasis group and healthy control group (P < 0.05). In the bone metastasis group, the levels of serum CX3CL1 and CX3CR1 were significantly positively correlated with the degree of disease progression (P < 0.01). Conclusion The expression level of serum CX3CL1–CX3CR1 axis is expected to be an auxiliary reference index for monitoring bone metastasis of lung cancer (AU)

Nuevos biomarcadores en la terapia de resincronización cardiaca. El factor de crecimiento hepatocitario es un predictor de los resultados clínicos / Novel biomarkers in cardiac resynchronization therapy: hepatocyte growth factor is an independent predictor of clinical outcome

Introducción y objetivos: La terapia de resincronización cardiaca (TRC) es beneficiosa para pacientes seleccionados con insuficiencia cardiaca (IC), aunque la ausencia de respuesta a la terapia es aún prevalente. Se investiga un conjunto de nuevos biomarcadores asociados a varias vías fisiopatológicas de la IC. El propósito fue valorar su capacidad para predecir los resultados clínicos con la TRC. Métodos: Se estudió a 136 pacientes con IC crónica y TRC. Se midieron los valores plasmáticos de fractalquina, pentraxina-3, factor de crecimiento hepatocitario (HGF), el antígeno carbohidrato 125 y la metaloproteinasa de matriz 9 tanto antes como 6 meses después del inicio de la TRC. El objetivo primario del estudio fue la mortalidad por todas las causas a 5 años, y se consideró la ausencia de remodelado inverso a los 6 meses (definido como al menos un 15% de descenso del volumen telesistólico) como un objetivo secundario. Resultados: Cincuenta y ocho pacientes fallecieron a lo largo de los 5 años de seguimiento y 66 pacientes se categorizaron como no respondedores. En modelos multivariables, solo un aumento del HGF resultó un predictor independiente, tanto de mortalidad (HR = 1,35; IC95%, 1,11-1,64; p = 0,003; por cada unidad de incremento de la desviación estándar) como de ausencia de remodelado inverso (OR = 1,83; IC95%, 1,10-3,04; p = 0,01; por cada unidad de incremento de la desviación estándar). Aplicando el HGF al modelo básico multivariable tanto de mortalidad (mejora neta de reclasificación = 0,69; IC95%, 0,39-0,99; p < 0,0001; mejora de discriminación integrada = 0,06; IC95%, 0,02-0,11) como de remodelado inverso (mejora neta de reclasificación = 0,39; IC95%, 0,07-0,71; p = 0,01; mejora de discriminación integrada = 0,03; IC95%, 0,00-0,06) se obtuvo una mejora estadísticamente significativa de reclasificación y discriminación. Conclusiones: De los biomarcadores investigados, solo el HGF predijo los resultados clínicos después de la TRC independientemente de otros parámetros. Los análisis de reclasificación mostraron que las mediciones de HGF podrían ser útiles para mejorar la selección de pacientes

Introduction and objectives: Cardiac resynchronization therapy (CRT) is beneficial for selected heart failure (HF) patients, although nonresponse to therapy is still prevalent. We investigated a set of novel biomarkers associated with various pathophysiological pathways of HF. Our purpose was to assess their ability to predict clinical outcomes after CRT. Methods: We studied 136 chronic HF patients undergoing CRT. We measured the plasma levels of fractalkine, pentraxin-3, hepatocyte growth factor (HGF), carbohydrate antigen-125, and matrix metalloproteinase-9 before and 6 months after CRT. The primary endpoint of the study was 5-year all-cause mortality, and we considered the absence of 6-month reverse remodelling (defined as at least a 15% decrease in end-systolic volume) as a secondary endpoint. Results: Fifty-eight patients died during the 5-year follow-up period and 66 patients were categorized as nonresponders. In multivariable models, only an increased HGF was an independent predictor of both mortality (HR, 1.35; 95%CI, 1.11-1.64; P = .003; per 1 standard deviation increase) and the absence of reverse remodelling (OR, 1.83; 95%CI, 1.10-3.04; P = .01; per 1 standard deviation increase). Applying HGF to the basic multivariable model of both mortality (net reclassification improvement = 0.69; 95%CI, 0.39-0.99; P < .0001; integrated discrimination improvement = 0.06; 95%CI, 0.02-0.11) and reverse remodelling (net reclassification improvement = 0.39; 95%CI, 0.07-0.71; P = .01; integrated discrimination improvement = 0.03; 95%CI, 0.00-0.06) resulted in a statistically significant reclassification and discrimination improvement. Conclusions: Of the investigated biomarkers, only HGF predicted clinical outcomes following CRT independently of other parameters. Reclassification analyses showed that HGF measurements could be useful in refining patient selection