Protein predictive signatures for lymph node metastasis of gastric cancer

Lymph node status remains one of most crucial indicators of gastric cancer prognosis and treatment planning. Current imaging methods have limited accuracy in predicting lymph node metastasis. We sought to identify protein markers in primary gastric cancer and to define a risk model to predict lymph node metastasis. The Protein Pathway Array (PPA) (initial selection) and Western blot (confirmation) were used to assess the protein expression in a total of 190 freshly frozen gastric cancer samples. The protein expression levels were compared between samples with lymph node metastasis (n = 73) and those without lymph node metastasis (n = 57) using PPA. There were 27 proteins differentially expressed between lymph node positive samples and lymph node negative samples. Five proteins (Factor XIII B, TFIIH p89, ADAM8, COX-2 and CUL-1) were identified as independent predictors of lymph node metastasis. Together with vascular/lymphatic invasion status, a risk score model was established to determine the risk of lymph node metastasis for each individual gastric cancer patient. The ability of this model to predict lymph node metastasis was further confirmed in a second cohort of gastric cancer patients (33 with and 27 without lymph node metastasis) using Western blot. This study indicated that some proteins differentially expressed in gastric cancer can be selected as clinically useful biomarkers. The risk score model is useful for determining patients' risk of lymph node metastasis and prognosis.