Dataset Information

Identification of ABCA5 among ATP-Binding Cassette Transporter Family as a New Biomarker for Colorectal Cancer.

ABSTRACT:

Background

The increasing incidence and mortality of colorectal cancer (CRC) urgently requires updated biomarkers. The ABC transporter family is a widespread family of membrane-bound proteins involved in the transportation of substrates associated with ATP hydrolysis, including metabolites, amino acids, peptides and proteins, sterols and lipids, organic and inorganic ions, sugars, metals, and drugs. They play an important role in the maintenance of homeostasis in the body.

Purpose

This study aims to search for new markers in the ABC transporter gene family for diagnostic and prognostic purposes through data mining of The Cancer Genome Atlas (TCGA) and GEO (Gene Expression Omnibus) datasets.

Methods

A total of 980 samples, including 684 CRC patients and 296 controls from five different datasets, were included for analysis. The construction of the PPI (protein-protein interaction) network and pathway analysis were performed in STRING database and DAVID (database for annotation, visualization, and integrated discovery), respectively. In addition, GSEA (gene set enrichment analysis) and WGCNA (weighted gene co-expression network analysis) were also used for functional analysis.

Results

After several rounds of screening and validation, only the ABCB5 gene was retained among the 49 genes.

Conclusions

The results demonstrated that ABCA5 expression is reduced in CRC and patients with high ABCA5 expression have better OS, which can provide guidance for better management and treatment of CRC in the future.

SUBMITTER: Bu P

PROVIDER: S-EPMC9242773 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeLiver 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 methodsData 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.ResultsAmong 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.ConclusionABCC5 may facilitate LIHC progression through different mechanisms and be a potential biomarker and target for diagnosis, prognosis, and therapy of LIHC.