Molecular markers for preoperative prediction of lymph node metastasis in gastric cancer / 中华消化杂志

ABSTRACT

Objective:To evaluate the clinical prognostic significance of molecular markers with high predictive value for lymph node metastasis (LNM) before operation in gastric cancer (GC).Methods:From January 2013 to December 2015, at Peking University Third Hospital, 85 patients with GC confirmed by preoperative biopsy under gastroendoscopy and receiving radical gastrectomy were selected. Among 85 patients with GC, 34 patients had LNM and the other 51 patients were without LNM. The expression levels of macrophage capping protein G (CapG), tyrosine kinase receptor B (TrkB), prosperohomeobox protein l (Prox-1), matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor-C (VEGF-C) and vascular endothelial growth factor receptor 3 (VEGFR3) were detected by immunohistochemistry (IHC) in preoperative gastric biopsy tissues. Chi-square test was performed to analyze the correlation between the expression of different markers and various clinicopathological characteristics. Receiver operating characteristic (ROC) curve was drawn to compare the predictive value of different markers on LNM of GC. Kaplan-Meier curve was applied to evaluate the impact of different markers on the prognosis of GC patients.Results:The positive expression rates of CapG, TrkB, Prox-1, MMP-2, VEGF-C and VEGFR3 of the LNM-positive group were higher than those of the LNM-negative group (85.3%, 29/34 vs. 35.3%, 18/51; 76.5%, 26/34 vs. 29.4%, 15/51; 67.6%, 23/34 vs. 11.8%, 6/51; 64.7%, 22/34 vs. 33.3%, 17/51; 61.8%, 21/34 vs. 29.4%, 15/51; 52.9%, 18/34 vs. 23.5%, 12/51, respectively), and the differences were statistically significant ( χ2=20.631, 18.093, 28.342, 8.086, 8.746 and 7.727, all P<0.01). The area under the ROC curve (AUC) values and 95% confidence interval ( CI) of CapG, TrkB, Prox-1, MMP-2, VEGF-C and VEGFR3 in predicting LNM of GC before operation were 0.787 (0.687 to 0.880), 0.772 (0.656 to 0.860), 0.761 (0.661 to 0.883), 0.724 (0.618 to 0.830), 0.687 (0.571 to 0.803) and 0.583 (0.452 to 0.715), respectively. Among them, the AUC values of CapG, Prox-1 and TrkB were relatively high. The expression levels of CapG and Prox-1 were correlated with invasion depth and TNM stage of GC ( χ2=4.792, 13.664, 4.204 and 19.948, all P<0.05). And TrkB expression was correlated with TNM stage of GC ( χ2=12.036, P<0.05). Kaplan-Meier curves revealed that the overall survival rates of CapG, TrkB or Prox-1 positive groups were significantly lower than those of CapG, TrkB or Prox-1 negative groups (70.2%, 33/47 vs. 94.7%, 36/38; 70.7%, 29/41 vs. 90.9%, 40/44; 69.0%, 20/29 vs. 87.5%, 49/56, respectively), and the differences were statistically significant ( χ2=9.820, 4.909 and 4.683, all P<0.05). Conclusions:CapG, TrkB and Prox-1 are markers with relatively high predictive value for LNM of GC, and all of them are correlated with the progression and poor prognosis of GC.