RESUMEN
The meta-analysis was conducted to evaluate the correlations between common genetic polymorphisms in the IFN-γ gene and susceptibility to breast cancer. The following electronic databases were searched without language restrictions: MEDLINE (1966 ~ 2013), the Cochrane Library Database (issue 12, 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), Web of Science (1945 ~ 2013), and the Chinese Biomedical Database (CBM) (1982 ~ 2013). Meta-analysis was performed with the use of the STATA statistical software. Odds ratios (OR) with their 95 % confidence intervals (95 % CIs) were calculated. Nine clinical case-control studies met all the inclusion criteria and were included in this meta-analysis. A total of 1,182 breast cancer patients and 1,525 healthy controls were involved in this meta-analysis. Three functional polymorphisms were assessed, including rs2069705 C>T, rs2430561 T>A, and CA repeats 2/X. Our meta-analysis results indicated that IFN-γ genetic polymorphisms might be significantly associated with an increased risk of breast cancer (allele model: OR = 1.37, 95 % CI = 1.03 ~ 1.83, P = 0.031; dominant model: OR = 1.55, 95 % CI = 1.01 ~ 2.37, P = 0.046; homozygous model: OR = 2.23, 95 % CI = 1.30 ~ 3.82, P = 0.004; respectively), especially the rs2430561 T>A polymorphism. Subgroup analysis based on ethnicity suggested that genetic polymorphisms in the IFN-γ gene were closely correlated with increased breast cancer risk among Asians (allele model: OR = 1.21, 95 % CI = 1.02 ~ 1.58, P = 0.017; dominant model: OR = 3.44, 95 % CI = 2.07 ~ 5.71, P < 0.001; recessive model: OR = 1.58, 95 % CI = 1.06 ~ 2.37, P = 0.025; homozygous model: OR = 1.83, 95 % CI = 1.19 ~ 2.80, P = 0.006; respectively), but not among Caucasians (all P > 0.05). Our meta-analysis supported the hypothesis that IFN-γ genetic polymorphisms may contribute to an increased risk of breast cancer, especially the rs2430561 T>A polymorphism among Asians.
Asunto(s)
Neoplasias de la Mama/genética , Predisposición Genética a la Enfermedad , Interferón gamma/genética , Pueblo Asiatico/genética , Neoplasias de la Mama/patología , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Humanos , Factores de Riesgo , Población Blanca/genéticaRESUMEN
Approximately 10% of lung adenocarcinomas harbor aberrations that are targetable using the approved multitargeted TKI crizotinib. MET exon 14 skipping mutation predicts for response to crizotinib in human lung adenocarcinomas. However, a substantial part of patients still has no sufficient tissue to perform genomic analysis. As a promising noninvasive biomarker and potential surrogate for the entire tumor genome, circulating tumor DNA (ctDNA) has been applied to the detection of driver gene mutations. Here we described the MET exon 14 splicing mutations in cell-free circulating-tumor DNA by next-generation sequencing (NGS) technology. Patient firstly responded to crizotinib therapy within four months, however, three acquired mutation in the MET kinase domain, D1228N/H and Y1230H, were found at the time of disease progression. To our knowledge, this is the first clinical report of three mutations simultaneously arising in a patient with MET exon 14 splicing mutation.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogénicas c-met/genética , Pirazoles/farmacología , Piridinas/farmacología , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología , Adenocarcinoma del Pulmón , Empalme Alternativo , Antineoplásicos/uso terapéutico , Pueblo Asiatico , ADN Tumoral Circulante/genética , Crizotinib , Progresión de la Enfermedad , Resistencia a Antineoplásicos , Exones , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Mutación , Inhibidores de Proteínas Quinasas/farmacología , Tomógrafos Computarizados por Rayos X , Resultado del TratamientoRESUMEN
AIM: To analyze the expression of kallikrein gene 10 (KLK10) in gastric cancer and to determine whether KLK10 has independent prognostic value in gastric cancer. METHODS: We studied KLK10 expression in 80 histologically confirmed gastric cancer samples using real-time quantitative reverse transcription-PCR and hK10 expression using immunohistochemistry. Correlations with clinicopathological variables (lymph node metastasis, depth of invasion and histology) and with outcomes (disease-free survival and overall survival) during a median follow-up period of 31 mo were assessed. Gastric cancer tissues were then classified as KLK10 positive or negative. RESULTS: KLK10 was found to be highly expressed in 57/80 (70%) of gastric cancer samples, while its expression was very low in normal gastric tissues. Positive relationships between KLK10 expression and lymph node metastasis (P = 0.048), depth of invasion (P = 0.034) and histology (P = 0.015) were observed. Univariate survival analysis revealed that gastric cancer patients with positive KLK10 expression had an increased risk for relapse/metastasis and death (P = 0.005 and 0.002, respectively). Cox multivariate analysis indicated that KLK10 was an independent prognostic indicator of disease-free survival and overall survival in patients with gastric cancer. CONCLUSION: KLK10 expression is an independent biomarker of unfavorable prognosis in patients with gastric cancer.
Asunto(s)
Biomarcadores de Tumor/análisis , Calicreínas/análisis , Neoplasias Gástricas/enzimología , Adulto , Anciano , Biomarcadores de Tumor/genética , Distribución de Chi-Cuadrado , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Calicreínas/genética , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , ARN Mensajero/análisis , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Riesgo , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Neoplasias Gástricas/terapia , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia ArribaRESUMEN
PURPOSE: To determine the optimal standardized uptake value (SUV) of (18)F-fluorodeoxyglucose ((18)F-FDG) for positron emission tomography (PET) imaging, at which the PET-defined gross tumor volume (GTVPET) best matches with the pathological volume (GTVPATH) in the cervical cancer. MATERIALS AND METHODS: Ten patients with the cervical cancer who underwent surgery were enrolled in this study. The excised specimens were processed for whole-mount serial sections and H-E staining. The tumor borders were outlined in sections under a microscope, histopathological images were scanned and the GTVPATH calculated. The GTVPET was delineated automatically by using various percentages relative to the maximal SUV and absolute SUV. The optimal threshold SUV was further obtained as the value at which the GTVPET best matched with the GTVPATH. RESULTS: An average of 85 ± 10% shrinkage of tissue was observed after the formalin fixation. The GTVPATH was 13.38 ± 2.80 cm(3) on average. The optimal threshold on percentile SUV and absolute SUV were 40.50% ± 3.16% and 7.45 ± 1.10, respectively. The correlation analysis showed that the optimal percentile SUV threshold was inversely correlated with GTVPATH (p<0.05) and tumor diameter (p<0.05). The absolute SUV was also positively correlated with SUVmax (p<0.05). CONCLUSION: The pathological volume could provide the more accurate tumor volume. The optimal SUV of FDG for PET imaging by use of GTVPATH as standard for cervical cancer target volume delineation was thus determined in this study, and more cases are being evaluated to substantiate this conclusion.