RESUMEN
Leukemia inhibitory factor receptor (LIFR) has been documented as a cancer promoter and to be present at high levels in various types of tumor tissues. In our search for molecules prognostic of colorectal cancer (CRC), we found high levels of LIFR in CRC tissue samples. Further analyses revealed that LIFR was indeed prognostic of CRC patient survival, and was associated with tumor size, lymphatic metastasis and stages. LIFR was found to promote tumor growth, metastasis and angiogenesis both in vitro and in vivo. High levels of LIFR in CRC facilitated proliferation and migration of endothelial cells, resulting in an increase in angiogenic activity. Moreover, interleukin 8 (IL-8) was found to play a role in the LIFR induced angiogenesis. IL-8 levels were correlated with LIFR levels in CRC tissues, whereas depletion of IL-8 led to a reduced angiogenic activity of LIFR in CRC cells. In addition, LIFR increased phosphorylation level of Erk, which regulates il-8 transcription. We conclude that LIFR is possibly a valuable prognostic marker for CRC. Our results also implicate a mechanism by which LIFR regulates tumor angiogenesis through Erk/IL-8 pathway, and that LIFR could be a potential therapeutic target for CRC.
Asunto(s)
Neoplasias Colorrectales/irrigación sanguínea , Células Endoteliales/patología , Interleucina-8/metabolismo , Subunidad alfa del Receptor del Factor Inhibidor de Leucemia/metabolismo , Neovascularización Patológica/patología , Anciano , Animales , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Regulación hacia Abajo , Femenino , Estudios de Seguimiento , Células Endoteliales de la Vena Umbilical Humana , Humanos , Interleucina-8/genética , Subunidad alfa del Receptor del Factor Inhibidor de Leucemia/genética , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Neovascularización Patológica/mortalidad , Pronóstico , ARN Interferente Pequeño/metabolismo , Regulación hacia Arriba , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: To investigate the clinical significance of plasmic L-plastin level in patients with colorectal cancer. METHODS: From March 2008 to March 2009, plasma samples were collected from 40 patients and 40 healthy controls. Plasmic L-plastin level was measured by ELISA kit and was compared to TIMP-1. RESULTS: Plasmic L-plastin level in patients with colorectal cancer was higher than that in healthy adults (1.662±0.386 vs. 0.485±0.085 µg/L, P<0.01). The sensitivity of L-plastin in the diagnosis of colorectal cancer was 67.5%, and the specificity was 80.6%. The Youden index was 0.481 and AUC was 0.772 (P<0.01). Plasmic L-plastin levels were associated with the tumor size (P=0.006), serosal penetration (F=4.687, P<0.05) and lymphatic metastasis (P<0.01). Compared to plasmic TIMP-1 level, L-plastin showed the same capability in indicating the depth of tumor. The specificity of L-plastin was better in indicating lymphatic metastasis (86% vs. 58%, χ2=4.2, P<0.05). CONCLUSIONS: Plasmic L-plastin level may serve as a potential marker in colorectal cancer.
Asunto(s)
Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/diagnóstico , Glicoproteínas de Membrana/sangre , Proteínas de Microfilamentos/sangre , Anciano , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Inhibidor Tisular de Metaloproteinasa-1/sangreRESUMEN
BACKGROUND: The present study was designed to specifically investigate the clinicopathological role of expression of cortactin, as well as the correlation with clinical outcomes in stages II-III colorectal cancer (CRC). METHODS: Two hundred and five stages II-III CRC patients were included in this study. Formalin-fixed paraffin-embedded specimens were stained for cortactin and the correlation between the staining, its clinicopathological parameters, and its prognostic power were analyzed statistically. RESULTS: Of the 205 patients studied, 113 cases (55.1%) were strongly positive for cortactin. Cortactin expression correlated with tumor invasion (P = 0.018), histological grade (P = 0.004), and preoperative CEA level (P < 0.001). In univariate analysis, tumor invasion, American Joint Committee on Cancer (AJCC) stage, lymphovascular invasion, preoperative CEA level, and cortactin expression were significant prognostic factors for disease-free survival (P = 0.034, 0.009, 0.043, 0.004, and 0.004, respectively), while for overall survival, tumor invasion, AJCC stage, pathologic grade, preoperative CEA level, and cortactin expression were significant prognostic factors (P = 0.003, 0.008, 0.038, 0.017, and <0.001, respectively). In multivariate analysis, tumor invasion, preoperative CEA level, and cortactin expression maintained their independent prognostic influence on disease-free survival (P = <0.001, 0.003, and 0.008, respectively). However, tumor invasion, AJCC stage, and cortactin expression influenced overall survival (P = 0.036, <0.001, and 0.004, respectively). CONCLUSIONS: Cortactin may be a good biomarker to be applied in the clinical setting to predict the prognosis of patients with completely resected pathologic stages II-III CRC.