Identification of molecular biomarkers for the diagnosis of gastric cancer and lymph-node metastasis

Abstract

Background and objective: Biomarkers are important tools for prompt diagnosis of cancer. This study aimed to identify reliable biomarkers for clinical applications in the diagnosis of gastric cancer and lymph-node (LN) metastasis. Methods: Between 1 December 2014 and 31 December 2015, we prospectively collected samples of gastric-cancer tissues, corresponding matched-pair normal gastric mucosa, and their peri-gastric metastatic and non-metastatic LNs to identify quantitatively reliable genes using quantitative real-time polymerase chain reaction. Relative quantity (RQ) was used to calculate the mRNA expression levels of our target genes. Statistics were calculated using one-way analysis of variance (ANOVA) and Tukey's multiple comparison test. Analytical graphs were plotted using GraphPad Prism. Results: Of nine assessed genes, the mRNA levels of inhibin beta A (INHBA) and secreted phosphoprotein 1 (SPP1) were most consistently highly expressed in tumor tissues by 15.4- and 15.6-fold, respectively, as compared with normal tissues (P < 0.001), with 91.3% sensitivity and 95.7% specificity (receiver operating characteristic [ROC] curve area ¼ 0.974) for the former and 82.6% sensitivity and 87.0% specificity (ROC curve area ¼ 0.924) for the latter. Further analysis revealed no differentiating significance of SPP1 mRNA expression between metastatic and non-metastatic LNs (P ¼ 0.470). In contrast, the INHBA mRNA level was up-regulated 4.1-fold in metastatic LNs (P < 0.001), with 80.0% sensitivity and 81.5% specificity (ROC curve area ¼ 0.857), and was also able to successfully differentiate between more severe disease conditions, T3 and T4 (P ¼ 0.003), M0 and M1 (P ¼ 0.043) and different histological variants (intestinal type vs diffuse type, P ¼ 0.019). Conclusions: Our results showed that INHBA was the most optimally reliable biomarker for diagnosing gastric cancer and LN metastasis.