Prognostic significance and molecular mechanisms of adenosine triphosphate-binding cassette subfamily C members in gastric cancer.

Abstract

Gastric cancer (GC) is one of the major leading causes of tumor-related deaths worldwide. Adenosine triphosphate-binding cassette subfamily C (ABCC) consists of 13 members, ABCC1 to 13, which were examined for their associations with GC.The online Kaplan-Meier Plotter database was used to determine the prognostic significance of ABCC subfamily members in GC. Stratified analyses were performed using gender, disease stage, degree of tumor differentiation, expression of human epidermal growth factor receptor 2 (HER2), and Lauren classification. Molecular mechanisms were examined using the database for annotation, visualization, and integrated discovery database.ABCC1, ABCC3, ABCC7, ABCC8, ABCC9, and ABCC10 expression showed prognostic significance in the whole population and in male and female subpopulations (all P ≤ .05). Furthermore, high expression of most ABCC family members always suggested a poor prognosis, except for ABCC7 (P > .05). Stratified analyses revealed that ABCC1, ABCC3, ABCC7, ABCC8, ABCC9, and ABCC10 expression showed prognostic significance for the whole population, as well as male and female populations. ABCC2 and ABCC9 were significantly correlated with all disease stages, while ABCC2 and ABCC6 were significantly correlated with all Lauren classifications. Expression of ABCC1, ABCC3, ABCC5, ABCC7, ABCC8, ABCC9, and ABCC10 was significantly correlated with either negative or positive of HER2 status (all P ≤ .05). Enrichment analysis indicated that these genes were involved in ATPase activity, transmembrane transport, or were ABC transporters (all P ≤ .05).ABCC1, ABCC3, ABCC7, ABCC8, ABCC9, and ABCC10 may be potential prognosis biomarkers for GC, acting as ABC transporters and via ATPase activity.