Prognostic implications of serum microRNA-21 in colorectal cancer.

BACKGROUND AND OBJECTIVES: MicroRNAs (miRNAs) are small, noncoding RNAs that are involved in carcinogenesis through postranscriptional gene regulatory activity. Few studies have focused on the detection of miR-21 in serum rather than in tissue. The current study aimed to measure serum miR-21 expression levels and to evaluate their association with the outcome of colorectal cancer (CRC). METHODS: Blood samples were collected from 102 CRC patients undergoing surgery with curative intent. The expression levels of miR-21 were measured using a quantitative reverse transcription polymerase chain reaction (qRT-PCR). The results were analysed to assess the relationship between serum miR-21 levels and patient survival. RESULTS: A univariate analysis revealed that lower expression levels of serum miR-21 were associated with higher local recurrence (P = 0.025) and mortality (P = 0.029). A logistic regression analysis demonstrated that the relative overexpression of miR-21 (expression > 1) was associated with a 51% reduction in the risk of recurrence. A Cox regression analysis identified miR-21 expression as an independent predictor of survival (P = 0.048); a relative increase in miR-21 expression (>1) was associated with a 50% reduction in the risk of mortality. CONCLUSION: The expression level of serum miR-21 correlates with the recurrence and mortality of CRC patients. Our results suggest that circulating serum miR-21 is a promising prognostic tumour marker, and they highlight the potential clinical utility of miR-21 expression as a prognostic marker for CRC prognosis.

[Serum vascular endothelial growth factor levels in patients with colorectal cancer and its prognostic significance]. / Valores séricos de factor de crecimiento del endotelio vascular en pacientes con cáncer colorrectal y su significación pronóstica.

BACKGROUND AND OBJECTIVE: Thirty per cent of patients with histologically node-negative colorectal cancer die from disseminated disease. Actually disease stage is the most useful prognostic parameter although it is not sufficient. Vascular endothelial growth factor (VEGF) is an angiogenic cytokine involved in the progression of tumors. In our study we tried to know the prognostic significance of pre and postoperative serum VEGF levels in patients with colorectal cancer. PATIENTS AND METHOD: Cohort study that included 52 patients with colorectal cancer surgically treated in our Department from 1998 to 2000. Serum VEGF and CEA levels were determined the day before surgery and 30 days after it. RESULTS: Preoperative serum VEGF levels (428.5 [38.5] pg/ml) were higher than in control patients (p=0.008). Serum VEGF levels fallen significantly after surgery (343 [31.2] pg/ml; p=0.001). Pre and postoperative serum VEGF levels in poorly differentiated neoplasms were higher than in well differentiated ones (p=0.009 and p=0.008 respectively). Pre and postoperative serum CEA and VEGF levels were significantly associated with cancer relapse (p=0.037, p=0.017, p=0.048 and p=0.001, respectively). In multivariate analysis only postoperative serum VEGF levels were associated with colorectal cancer relapse (p=0.003; HR=1.007; 95% CI, 1.002-1.012). Pre and postoperative CEA levels (p<0.001 and p=0.001 respectively) and postoperative VEGF levels (p=0.001), were associated with mortality. In multivariate analysis only tumor stage (p=0.01) and postoperative serum VEGF levels (p=0.02) were associated with mortality. Postoperative serum VEGF determination and pre and postoperative CEA levels raise specificity and positive predictive values to 100% in relation to mortality. CONCLUSIONS: Pre and postoperative serum VEGF determination has prognostic significance, regardless of tumor stage, in patients with colorectal cancer. In survival methods, postoperative VEGF levels >343 pg/ml are significantly with tumor relapse and mortality. These results suggest the use of serum VEGF levels as a prognostic and monitoring factor besides CEA.

Valores séricos de factor de crecimiento del endotelio vascular en pacientes con cáncer colorrectal y su significación pronóstica / Serum vascular endothelial growth factor levels in patients with colorectal cancer and its prognostic significance

FUNDAMENTO Y OBJETIVO: Un tercio de los enfermos con cáncer colorrectal intervenidos quirúrgicamente con intención curativa fallece a consecuencia de una recidiva de la enfermedad. La estadificación anatomopatológica constituye el indicador pronóstico más fiable, aunque resulta insuficiente. Intentamos conocer el valor pronóstico de la determinación sérica pre y postoperatoria del factor de crecimiento del endotelio vascular (VEGF) en enfermos con cáncer colorrectal. PACIENTES Y MÉTODO: Se realizó un estudio de cohorte de 52 enfermos con cáncer colorrectal intervenidos quirúrgicamente en nuestro Servicio (Complejo Hospitalario de Ciudad Real) con carácter electivo entre 1998 y 2000. Se determinaron las concentraciones séricas de VEGF y antígeno carcinoembrionario (CEA), el día previo a la intervención quirúrgica y 30 días después. RESULTADOS: Los valores preoperatorios de VEGF en enfermos con cáncer colorrectal (media de 430,8 [38,5] pg/ml) son más elevados que en los controles (p = 0,008). A los 30 días de la intervención quirúrgica hubo un descenso significativo de los valores de VEGF (343 [31,2] pg/ml; p < 0,0001). Las neoplasias con mala diferenciación presentaron valores pre y postoperatorios más elevados (p = 0,009 y p = 0,008, respectivamente) que aquellas con buena diferenciación. Los valores pre y postoperatorios de VEGF y CEA se relacionaron significativamente con la recidiva de la enfermedad (p = 0,037, p = 0,017, p = 0,048 y p = 0,001, respectivamente). En el estudio multivariante sólo los valores postoperatorios de VEGF se relacionaron con recidiva de la enfermedad (p = 0,003; razón de riesgo = 1,007; intervalo de confianza del 95 por ciento, 1,002-1,012). Los valores pre y postoperatorios de CEA (p < 0,001 y p = 0,001, respectivamente) y postoperatorios de VEGF (p = 0,001) se relacionaron con una menor supervivencia de los enfermos. En el análisis multivariante, sólo la estadificación anatomopatológica (p = 0,01) y los valores de VEGF (p = 0,02) se relacionaron con la mortalidad. La determinación sérica de VEGF en el postoperatorio, junto a las determinaciones pre y postoperatoria de CEA, incrementó la especificidad y el poder predictivo positivo al 100 por ciento respecto a la mortalidad del enfermo. CONCLUSIONES: La determinación sérica pre y postoperatoria de VEGF puede considerarse un marcador pronóstico relevante, independiente de la estadificación neoplásica en el cáncer colorrectal. Valores postoperatorios superiores a 343 pg/ml, en modelos uni y multivariantes, se relacionan significativamente con la recidiva y mortalidad del enfermo, por lo que deberíamos valorar su utilización como marcador de seguimiento junto al CEA, habitualmente utilizado (AU)