High expression of oncogene cadherin-6 correlates with tumor progression and a poor prognosis in gastric cancer

• Published in: Cancer cell international Vol. 21; no. 1; pp. 1 - 493
• Main Authors: Zhao, Zongxian, Li, Shuliang, Li, Shilong, Wang, Jun, Lin, Hai, Fu, Weihua
• Format: Journal Article
• Language: English
• Published: London BioMed Central 16.09.2021; BMC
• Subjects: Biomarkers; Cadherin-6; Cadherins; Cancer therapies; Datasets; Diagnosis; Extracellular matrix; Gastric cancer; Gene expression; Gene set enrichment analysis; Genomes; Hospitals; Lymphatic system; Medical prognosis; Metastasis; Morphogenesis; Oncogene; Oncogenes; Ovaries; Oxidative metabolism; Oxidative phosphorylation; Patients; Pentose phosphate pathway; Phosphorylation; Polymerase chain reaction; Primary Research; Prognosis; Regression analysis; Risk factors; Statistical analysis; Survival; Survival analysis; Tricarboxylic acid cycle; Tumor progression; Tumors; Beijing China; China
• ISSN: 1475-2867; 1475-2867
• DOI: 10.1186/s12935-021-02071-y

Abstract Background Gastric 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. Methods The 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. Results CDH6 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). Conclusion CDH6 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.