VCAN – A novel prognostic marker for gastric cancer

Abstract

Background Versican (VCAN) is a large aggregating extracellular matrix proteoglycan implicated in the pathogenesis of most human cancers but its role in gastric cancer is not yet elucidated. We designed the present study to investigate the expression, prognostic value, relationship between genetic alterations and patient’s outcome, disease associations, as well as genetic and protein interactions of VCAN in gastric cancer. Methods Expression of VCAN in tumor and normal tissues was studied with ONCOMINE, UALCAN, and GEPIA databases and the human protein atlas. UALCAN, GEPIA, OncoLnc and Kaplan-Meier plotter were used to assess the prognostic values of VCAN in gastric cancer. Subgroup analysis of the clinical significance of VCAN in gastric cancer was done using Kaplan-Meier plotter. Genetic alterations of VCAN and their associations with patient’s outcome were studied with cBioPortal. Open targets platform was used to study diseases associated with VCAN, GeneMANIA was used to obtain the neighbor genes interaction network of VCAN, and STRING was used to examine VCAN interaction with other proteins. Results VCAN was upregulated and associated with clinical cancer stages. High VCAN expression predicted unfavorable outcome for all patients; subgroup analysis showed worse outcomes for patients treated with surgery or other adjuvants (other than 5-FU based adjuvant) but better outcome for patients treated with 5-FU based adjuvant, associating VCAN expression with chemosensitivity to 5-FU based adjuvants, but chemoresistance to other adjuvants. Genetic alteration of VCAN correlated with a favorable outcome in terms of disease-free survival for patients. Also, open targets platform showed that VCAN is associated with gastric cancer and is a potential therapeutic target for the disease. Finally, interaction of VCAN with neighbor genes and proteins revealed that VCAN interacts with genes and proteins that drive tumorigenesis and cancer progression. Conclusion The results of this study show that VCAN is an oncogene in gastric cancer whose expression can be applied as a biomarker for prognostic prediction, selection of appropriate chemotherapy drugs/monitoring of treatment response, and is a potential therapeutic target for gastric cancer.