Plasma CADM1 promoter hypermethylation and D-dimer as novel metastasis predictors of cervical cancer

摘要

Aim Cervical cancer (CC) is the fourth malignant tumor in women worldwide. The metastasis is still the major reason for the treatment failures of most CC patients. Cell adhesion molecule 1 (CADM1) promoter methylation and plasma D-dimer levels have been reported to be increased in many types of cancers. The purpose of this study was to investigate the value of combinatorial assay of plasma CADM1 promoter hypermethylation and D-dimer as a metastasis marker in CC. Methods Two hundred and ninety-two patients with newly diagnosed cervical diseases and 70 healthy women were enrolled. A validation set comprised 36 Stage I CC patients and followed for 3 years. Plasma CADM1 promoter methylation and D-dimer levels were detected. Results The total coincidence rate of CADM1 promoter methylation status was 93.3% between 45 pair-matched tissue and plasma samples. Plasma CADM1 methylation levels in CC patients were higher than other benign disease groups (P = 0.000). Plasma CADM1 methylation levels had statistically differences between CC patients with and without lymph node metastasis (P = 0.049) or in CC patients with and without distant metastasis (P = 0.000). Similarly, plasma D-dimer levels in CC patients were higher than other benign disease groups (P < 0.05). D-dimer levels were only statistically different between CC patients with and without distant metastasis (P = 0.003). Combined assay of the two parameters for metastasis prediction has high sensitivity (80.4%) and specificity (90.5%). Conclusion Combinatorial assay of plasma CADM1 methylation and D-dimer is a promising metastasis marker in cervical cancer.