Advanced gastric cancer is not controlled by surgery alone, although early gastric cancer can be cured by curative gastrectomy. The TNM factor, representing physical tumor spread, accurately predicts patient prognosis in advanced gastric cancer, however, more elaborate prognostic factors reflecting the malignant degree are necessary in order to determine the therapeutic target. The purpose of this study was to select a significant prognostic indicator of gastric cancer with curative intent, independent of TNM stage among daily-feasible clinical parameters. The current study included 382 patients with stage IB to III gastric cancer after curative surgery, in which the robust univariate prognostic predictors were age (p < 0.0001), lymph node metastasis density of 40% or over (ND40) (p < 0.0001), and preoperative high value of carcinoembryonic antigen (CEA) (preCEA) (p = 0.0012), as well as TNM stage, preoperative high value of CA19-9 (preCA19-9), a glyco-chain antigen recognized by monoclonal antibody NS19-9, and vascular invasion. In multivariate prognostic analysis, age (p = 0.0002), ND40 (p = 0.02), and preCEA (p = 0.03) remained independent prognostic factors. The ND-factor provided excellent prognostic stratification within the same stage, and stage III ND40 predicted a similar prognosis to stage IV and could be considered a non-curative factor. Interestingly, ND40 relevance was validated in the prospective and independent set of gastric cancer patients (p = 0.002).
Conclusion: The ND factor reflects the malignant degree of gastric cancer, and ND40 is a novel "non-curative factor" in gastric cancer patients. A search for the molecules associated with higher ND value within an identical stage could lead to objective determination of the degree of malignancy and development of novel strategies against advanced gastric cancer.