Background
There have been few available prognostic biomarkers in gastric cancer. We rigorously assessed the clinical relevance of promoter DNA methylation of
Cysteine dioxygenase type 1
(
CDO1
) gene, a cancer-specific aberration, in human gastric cancer.
Methods
Quantitative
CDO1
methylation value (TaqMeth V) was initially calculated in 138 gastric cancer patients operated in 2005, and its clinical significance was elucidated. As a subsequent expanded set, 154 gastric cancer patients with pathological stage (pStage) II / III with no postoperative therapy were validated between 2000 and 2010.
Results
(1) Median TaqMeth V of
CDO1
gene methylation of gastric cancer was 25.6, ranging from 0 to 120.9. As pStage progressed,
CDO1
TaqMeth V became higher (p < 0.0001). (2) The optimal cut-off value was determined to be 32.6; gastric cancer patients with high
CDO1
gene methylation showed a significantly worse prognosis than those with low
CDO1
gene methylation (p < 0.0001). (3) A multivariate cox proportional hazards model identified high
CDO1
gene methylation (p = 0.033) as an independent prognostic factor. (4) The results were recapitulated in the expanded set in pStage III, where high
CDO1
gene methylation group had a significantly worse prognosis than low
CDO1
gene methylation group (p = 0.0065). Hematogenous metastasis was unique in pStage III with high
CDO1
gene methylation (p = 0.0075). (5) Anchorage independent growth was reduced in several gastric cancer cell lines due to forced expression of the
CDO1
gene, suggesting that abnormal
CDO1
gene expression may represent distant metastatic ability.
Conclusions
Promoter DNA hypermethylation of
CDO1
gene was rigorously validated as an important prognostic biomarker in primary gastric cancer with specific stage.
Purpose With the widespread use of definitive chemoradiotherapy (dCRT) for esophageal squamous cell carcinoma (ESCC), salvage surgery for recurrence/residual patients became prevalent. However, survival impact of salvage surgery remains obscure at present. Methods The updated clinical outcomes of salvage surgery were investigated to know its survival impact. Of the 155 ESCC patients who underwent dCRT between 2009 and 2016, we included 85 patients with recurrence or residual disease. The median follow-up was 65 months. Results Of the 85 patients with progression disease, there were 42 and 43 patients of recurrence and residual disease, respectively. Salvage surgery was performed in 27 patients after dCRT, including 15 patients who underwent salvage esophagectomy. The 5year overall survival (OS) of salvage surgery and otherwise patients was 66.1% and 14.5%, and the patients with salvage surgery had a significantly better prognosis (p < 0.0001). In the 15 patients who underwent salvage esophagectomy, residual disease, lymph node metastasis-positive (ycN+) after dCRT, and pathological lymph node metastasis-positive (ypN+) were significantly associated with poor prognosis (p = 0.0492, p = 0.0006, p = 0.0276), and the 5-year OS rates for the ycN/ypN combinations were 90%, 33.3%, and 0% in ycN−/ypN−, ycN+/ypN−, and ycN+/ypN+ patients, respectively (p = 0.0026). In a multivariate analysis, ycN+ was an independent poor prognostic factor (HR 13.6, 95% CI 1.65-286.8, p = 0.0154). Conclusions Survival impact of salvage surgery after dCRT is robust, and lymph node metastasis after dCRT may help determine the indication for salvage esophagectomy.
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