Abstract
BackgroundGastric cancer (GC) is one of the most common and fatal cancers worldwide. Effective biomarkers to aid the early diagnosis of GC, as well as predict the course of disease, are urgently needed. Hence, we explored the role and function of cadherin-6 (CDH6) in the diagnosis and prognosis of gastric cancer.MethodsThe expression levels of CDH6 in cancerous and normal gastric tissue were analyzed using multiple public databases. Gene set enrichment analysis (GSEA) was performed using The Cancer Genome Atlas (TCGA) dataset. The diagnostic efficiency of CDH6 expression in GC patients was determined through receiver operating characteristic (ROC) curve analysis. The associations between clinical variables and CDH6 expression were evaluated statistically, and the prognostic factors for overall survival were analyzed by univariate and multivariate Cox regression. 44 GC tissue samples, 20 donor-matched adjacent normal tissue samples, and associated detailed clinical information, were collected from the Tianjin Medical University General Hospital. CDH6 expression levels were determined for further validation.ResultsCDH6 was upregulated in GC samples compared to normal gastric tissue. Furthermore, GSEA identified the tricarboxylic acid (TCA) cycle, extracellular matrix (ECM) receptor interaction, glyoxylate and dicarboxylate metabolism, oxidative phosphorylation, and the pentose phosphate pathway as differentially enriched in GC tissue samples. According to the area under the ROC curve (AUC) values (AUC = 0.829 in the TCGA and 0.966 in the GSE54129 dataset), CDH6 expression was associated with high diagnostic efficacy. Patients with high CDH6 levels in their GC tissues had a higher T number (according to the TNM classification) and a worse prognosis than those with low CDH6 expression. Univariate and multivariate Cox regression analysis showed that CDH6 was an independent risk factor for overall survival (univariate: HR = 1.305, P = 0.002, multivariate: HR = 1.481, P < 0.001).ConclusionCDH6 was upregulated in GC, and high CDH6 expression was indicative of a higher T number and a worse prognosis. Therefore, CDH6 represents a potentially independent molecular biomarker for the diagnostic and prognostic prediction of GC.
Highlights
Gastric cancer (GC) is one of the most common and fatal cancers worldwide
CDH6 was upregulated in GC, and high CDH6 expression was indicative of a higher T number and a worse prognosis
CDH6 is highly expressed in GC According to The Cancer Genome Atlas (TCGA), CDH6 was highly expressed in 343 GC tissues as compared to the 30 normal tissues (P = 2.16e−09, Fig. 1a) and in 25 GC tissues compared to the donor-matched normal tissues (P = 1.069e−05, Fig. 1b)
Summary
Effective biomarkers to aid the early diagnosis of GC, as well as predict the course of disease, are urgently needed. We explored the role and function of cadherin-6 (CDH6) in the diagnosis and prognosis of gastric cancer. In order to increase the long-term survival of patients, further research is urgently needed to identify highly sensitive specific biomarkers for the early and accurate diagnosis of GC. Several studies have found that CDHs can participate in the promotion of tumorigenesis, tumor growth, and malignant progression, and can be exploited for the diagnosis and survival prediction or cancer patients, and even as therapeutic targets [8,9,10]. The transcriptional silencing or mutation of E-cadherin is correlated with familial diffuse GC, which may serve as a biomarker for early cancer diagnosis [11]. It has been shown that CDH2 could act as a potential prognostic and predictive biomarker for the grading and treatment of gliomas [12]
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