Identification of ABCC5 Among ATP-Binding Cassette Transporter Family as a New Biomarker for Hepatocellular Carcinoma Based on Bioinformatics Analysis

Abstract

Purpose

Liver cancer is the fifth most common type of cancer worldwide, and the ATP-binding cassette (ABC) transporter family has been widely accepted as a cause of multidrug resistance. This study was conducted to explore the potential value and mechanisms of the ABC transporter gene family in the liver hepatocellular carcinoma (LIHC).

Materials and Methods

Data were collected from different public databases. UALCAN, ONCOMINE, and GEPIA were used to retrieve a selection of differently expressed and pathological stage-related genes among the ABC family. Principal component analysis (PCA) was utilized for grouping, and its prognostic value was evaluated by univariate and multivariate Cox analyses. The co-expression pattern was constructed with UALCAN, and the functional analyses were carried out with DAVID. The correlation between the biomarker and immune infiltration, genetic alteration frequency, and drug sensitivity were explored with TIMER, cBioPortal, GDSC and CTRP, respectively. Finally, tSNE algorithm was used to explore the distribution of ABCC5 expressed cells.

Results

Among the ABC transporter family members, ABCC5 was differently expressed and strongly related to the pathological stage of LIHC. PCA divided patients of LIHC into two groups, and Cox analyses demonstrated that ABCC5 was an independent risk factor of LIHC. Functional analyses indicated that the genes were enriched in the pathways of transmembrane transporter, ATPase activity, and bile secretion. ABCC5 is also associated with immune infiltration of cells like macrophages, neutrophils, and dendritic cells. The genetic alteration frequency of ABCC5 confirmed its potential value in LIHC. In addition, several drugs were explored and found to be relevant to LIHC. The t-SNE showed that expression of ABCC5 was most concentrated in macrophages, followed by hepatocytes.

Conclusion

ABCC5 may facilitate LIHC progression through different mechanisms and be a potential biomarker and target for diagnosis, prognosis, and therapy of LIHC.

Keywords:

• LIHC
• bioinformatics analysis
• ATP-binding cassette transporter family
• ABCC5

Acknowledgments

This research was supported by the Digestive Medical Coordinated Development Center of Beijing Hospitals Authority under Grant No. XXZ0105; Special Scientific Research Fund for Tutor under Grant No. YYDSZX201901; Medical and Health Public Foundation of Beijing under Grant No. YWJKJJHKYJJ-B17262-067; and the Science and Technology Development Project of China State Railway Group under Grant No. N2019Z004. We thank the editors and reviewers for their comments and instruction, and thank each other for the support and encouragement in the writing process.

Disclosure

The authors report no conflicts of interest in this work.