In addition, significant associations between up-regulated miR-221 and down-regulated Apaf-1 expressions and clinical stage and lymph node (LN) metastasis (P< 0.001 for each) were found.
In MLH1-negative CRC, loss of APAF-1 was associated with metastasis (p-value=0.041), worse prognosis (p-value<0.001) and independently predicted shorter survival time (p-value<0.001).
In multivariate analysis, APAF-1 and DAPK-1 methylation levels were independent prognostic markers for metastatic disease and death from renal cell carcinoma.
Loss of Apaf-1 expression may represent a marker of aggressive tumor behavior since it correlates significantly with the occurrence of lymph node metastasis in cervical cancer.
In addition, we found a significant negative correlation between APAF-1 expression level and tumor thickness and between primary melanomas and metastases.