RESUMEN
BACKGROUND/AIM: The spliceosome pathway, including Splicing Factor 3b Subunit 4 (SF3B4), plays an important role in carcinogenesis and progression in various cancers; however, the clinical relevance of SF3B4 in esophageal squamous cell carcinoma (ESCC) remains unknown. PATIENTS AND METHODS: SF3B4 expression was evaluated by real-time reverse transcription polymerase chain reaction in 80 ESCC patients. In order to explore the mechanism of SF3B4 in ESCC, the mRNA expression and copy number of SF3B4 were obtained from TCGA and we also implemented gene set enrichment analysis (GSEA). RESULTS: The high SF3B4 expression group (n=33) showed significantly more lymphatic permeation and poorer prognosis than the low SF3B4 expression group (n=47). GSEA revealed that high SF3B4 expression was correlated with genes associated with the transcription factor E2F and the G2/M checkpoint. SF3B4 expression was positively correlated with SF3B4 DNA copy number. CONCLUSION: Over-expression of SF3B4 may play a crucial role in the lymphatic progression of ESCC.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas de Esófago/genética , Factores de Empalme de ARN/genética , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Femenino , Humanos , Masculino , Pronóstico , Análisis de SupervivenciaRESUMEN
BACKGROUND/AIM: Fanconi anemia complementation group D2 (FANCD2) gene is vitally involved in DNA damage responses. We investigated the clinical significance of FANCD2 expression in hepatocellular carcinoma (HCC). PATIENTS AND METHODS: FANCD2 mRNA expression of resected HCC tissues was assessed in two HCC cohorts; Our cases (n=111), and The Cancer Genome Atlas (TCGA; n=371). Gene set enrichment analysis (GSEA) was conducted using the TCGA dataset. Proliferation and invasion assays were performed using siRNAs, and the effect of inhibition of the mechanistic target of rapamycin (mTOR) pathway was evaluated. RESULTS: FANCD2 expression was up-regulated in tumor tissues. Cases with high FANCD2 expression had poorer prognoses in both cohorts, and were associated with larger tumor size and invasive phenotypes. FANCD2 knockdown attenuated proliferation and invasion of HCC cells. FANCD2 expression was suppressed by mTOR inhibition. GSEA supported these findings. CONCLUSION: Elevated FANCD2 expression in HCC could be a novel biomarker for poor prognosis with potential therapeutic relevance.
Asunto(s)
Carcinoma Hepatocelular/metabolismo , Proteína del Grupo de Complementación D2 de la Anemia de Fanconi/metabolismo , Perfilación de la Expresión Génica , Neoplasias Hepáticas/metabolismo , Anciano , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/genética , Proliferación Celular , Estudios de Cohortes , Daño del ADN , Progresión de la Enfermedad , Proteína del Grupo de Complementación D2 de la Anemia de Fanconi/genética , Femenino , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Fenotipo , Pronóstico , ARN Interferente Pequeño/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
BACKGROUND/AIM: Homeobox B7 (HOXB7) gene is involved in various cellular functions. We investigated the clinical significance of HOXB7 expression in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: HOXB7 mRNA expression in 103 HCC samples and 58 matched non-cancerous liver tissues were examined by quantitative real-time polymerase chain reaction (qRT-PCR). HOXB7 protein expression was also examined by immunohistochemistry. Gene set enrichment analysis (GSEA) was performed using a public dataset. RESULTS: HOXB7 expression was significantly higher in HCC tissues than in liver parenchyma. Ten-year overall survival (OS) and 5-year recurrence-free survival (RFS) of cases with higher HOXB7 expression were significantly poorer than those with lower HOXB7 expression. HOXB7 expression was significantly associated with larger tumor size and higher rate of biliary invasion and constituted an independent prognostic factor for OS by multivariate analysis. These results were supported by GSEA. CONCLUSION: HOXB7 expression in HCC could be a novel biomarker for long-term prognosis after tumor resection.