ABCC1 is a predictive biomarker for prognosis and therapy in hepatocellular carcinoma

Y.-H. Han, Y.-Q. Wang, J.-Q. Bo, Y.-N. Guo, Q.-Q. Zhang, L.-X. Liu

Department of Gastroenterology and Hepatology, The First Hospital of Shanxi Medical University, Taiyuan, China. lixinliu6@hotmail.com

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• Hepatology
• Oncology

OBJECTIVE: Liver neoplasm is one of the most fatal malignancies worldwide, among which hepatocellular carcinoma (HCC) (MIM #114550, https://omim.org/) is the most prevalent type. ABCC1 (MIM *158343) is a membrane-bound protein that relies on ATP hydrolysis to transport substrates and is associated with tumour drug resistance and malignant potential. However, the relationship between ABCC1, HCC prognosis, and immune infiltration remains elusive.

MATERIALS AND METHODS: We analysed the mRNA expression of ABCC1 using data from public databases. Immunohistochemistry staining was performed to identify ABCC1 expression in tumour samples. We further investigated the correlation between ABCC1 and clinicopathological features. We investigated the connection between ABCC1 and HCC prognosis using survival and Cox regression analyses. We investigated the underlying pathways of ABCC1 in HCC using functional enrichment analysis and GSEA. We determine the relationship between ABCC1 and immune cell infiltration via an integrated immune landscape analysis.

RESULTS: Our investigation revealed the upregulation of ABCC1 expression in HCC (p < 0.01), which was verified in clinical samples (p < 0.01). In addition, ABCC1 is adversely associated with HCC clinical features and prognosis (p < 0.05). GO/KEGG analysis and GSEA identified that ABCC1 participates in multiple immune- and tumour-related pathways (p < 0.05). Immune cell infiltration analysis indicated that ABCC1 was positively correlated with various immune cells, among which, the strongest correlation was with macrophages (p < 0.001). Furthermore, we observed significant variations in immune checkpoints between the ABCC1-low and ABCC1-high groups (p < 0.01). This indicated that patients with a high expression of ABCC1 might respond poorly to immune checkpoint blockade (ICB) therapy (p = 9.2e–07).

CONCLUSIONS: Our study identified ABCC1 as a predictor of HCC prognosis and response to therapy.

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