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.Abbreviations: ABC = ATP-binding cassette, ABCC adenosine triphosphate-binding cassette subfamily C, ATP = adenosine triphosphate, BP = biological process, CC = cellular component, CI = confidence interval, DAVID = database for annotation, visualization and integrated discovery, GC = gastric cancer, GGI = gene-gene interaction, GO = gene ontology, HER2 = human epidermal growth factor receptor 2, HR = hazard ratio, KEGG = Kyoto Encyclopedia of Genes and Genomes, MF = molecular function, MRPs = multidrug resistance proteins, OS = overall survival.

Development of a Prognostic Five-Gene Signature with Radiotherapy Guidance Significance for Diffuse Lower-Grade Glioma Patients Based on Large-Scale Sequencing Data

“…ATP binding cassette subfamily C member 3(ABCC3), also named multidrug resistance-associated protein 3(MRP3), is an organic anion transporter and contributes to drug resistance of cancer cells [14]. Consistent with the results in this article, the poor prognosis predictive role of ABCC3 has been reported not only in acute myeloid leukemia [15], gastric cancer [16], pancreatic cancer [17] and lung cancer [18], but also in gliomas [19]. In addition to being found as a prognostic marker for gliomas in this article, structural maintenance of chromosomes 4(SMC4) has also been found to be a survival marker for colorectal cancer [20], breast cancer [21] and prostate cancer [22].…”

Multi-Omics Data Integration Analysis of an Immune-Related Gene Signature in LGG Patients With Epilepsy

“…Hence, a prognostic immunerelated gene signature was established. The ATP binding cassette subfamily C member 3 (ABCC3) gene belongs to the ABCC gene family encoding the ABC transporters and participates in transporting ATP-dependent substances across lipid membranes ( Chen and Tiwari, 2011;Mao et al, 2019). A high expression level of the ABCC3 gene is associated with various tumors' poor prognosis, such as gastric cancer, breast cancer, and pancreatic cancer (Adamska et al, 2019;Mao et al, 2019;Wang et al, 2020).…”

“…The ATP binding cassette subfamily C member 3 (ABCC3) gene belongs to the ABCC gene family encoding the ABC transporters and participates in transporting ATP-dependent substances across lipid membranes ( Chen and Tiwari, 2011;Mao et al, 2019). A high expression level of the ABCC3 gene is associated with various tumors' poor prognosis, such as gastric cancer, breast cancer, and pancreatic cancer (Adamska et al, 2019;Mao et al, 2019;Wang et al, 2020). Podoplanin (PDPN) is a glycoprotein receptor that affects cell behavior by interacting with other proteins and has various physiological functions (Krishnan et al, 2018).…”

Computational Drug Repositioning and Experimental Validation of Ivermectin in Treatment of Gastric Cancer

“…In the present study, we identified ivermectin in connection with cell proliferation, particularly towards the genes (e.g., members of the adenosine triphosphate (ATP)-binding cassette (ABC) transporters). ABC are a superfamily of membrane proteins which play significant roles in transporting various exogenous and endogenous substances across membranes against concentration gradients through ATP hydrolysis, and many of these transporters are known as multidrug resistance proteins (MRPs) ( Mao et al, 2019 ). As showed in the present study, ivermectin also acted on the ABC and the signaling pathways, leading to inhibition of cell proliferation by deactivating LXR/RXR signaling ( Beltowski, 2011 ; Saito-Hakoda et al, 2015 ).…”