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Adenosine triphosphate-binding cassette subfamily C members in liver hepatocellular carcinoma: Bioinformatics-driven prognostic value - PubMed

  • ️Sat Jan 01 2022

Adenosine triphosphate-binding cassette subfamily C members in liver hepatocellular carcinoma: Bioinformatics-driven prognostic value

Xiangtong Meng et al. Medicine (Baltimore). 2022.

Abstract

Aberrant expression of adenosine triphosphate-binding cassette subfamily C (ABCC), one of the largest superfamilies and transporter gene families of membrane proteins, is associated with various tumors. However, its relationship with liver hepatocellular carcinoma (LIHC) remains unclear.We used the Oncomine, UALCAN, Human Protein Atlas, GeneMANIA, GO, Kyoto Encyclopedia of Genes and Genomes (KEGG), TIMER, and Kaplan-Meier Plotter databases. On May 20, 2021, we searched these databases for the terms ABCC1, ABCC2, ABCC3, ABCC4, ABCC5, ABCC6, ABCC7, ABCC8, ABCC9, ABCC10, ABCC11, ABCC12, ABCC13, and "liver cancer." The exposure group comprised LIHC patients, and the control group comprised normal patients (those with noncancerous liver tissue). All patients shown in the retrieval language search were included. We compared the mRNA expression of these proteins in LIHC and control patients to examine the potential role of ABCC1-13 in LIHC.Relative to the normal liver tissue, mRNA expression of ABCC1/2/3/4/5/6/10 was significantly upregulated (P < .001), and that of ABCC9/11 significantly downregulated (both P < .001), in LIHC. ABCC mRNA expression varied with gender (P < .05), except for ABCC11-13; with tumor grade (P < 0.05), except for ABCC7/12/13; with tumor stage (P < .05), except for ABCC11-13; and with lymph node metastasis status (P < .05), except for ABCC7/8/11/12/13. Based on KEGG enrichment analysis, these genes were associated with the following pathways: ABC transporters, Bile secretion, Antifolate resistance, and Peroxisome (P < .05). Except for ABCC12/13, the ABCCs were significantly associated with B cell, CD8+ T cell, CD4+ T cell, macrophage, neutrophil, and dendritic cell infiltration (P < .05). High mRNA expression of ABCC1/4/5/8 (P < .05) and low expression of ABCC6/7/9/12/13 (P < .05) indicated poor prognosis. Prognostic significance was indicated for ABCC2/13 for both men and women (P < .05); for ABCC1/6/12/13 for tumor grades 1-3 (P < .05); for ABCC5/11/12/13 for all tumor stages (P < .05); for ABCC1/11/12/13 for American Joint Committee on Cancer T stages 1-3 (P < .05); and for ABCC1/5/6/13 for vascular invasion. None showed prognostic significance for microvascular invasion (P < .05).We identified ABCC1/2/3/4/5/6/9/10/11 as potential diagnostic markers, and ABCC1/4/5/6/7/8/9/12/13 as prognostic markers, of LIHC. Our future work will promote the use of ABCCs in the diagnosis and treatment of LIHC.

Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.

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Conflict of interest statement

The authors have no conflicts of interests to disclose.

Figures

Figure 1
Figure 1

Transcriptional expression of different ABCCs family members in 20 types of cancer. The data was compared by t-test. The cut-off P value and the fold change were as follows: P value <.0001, fold change = 1.5, gene grade = 10%. Red means overexpression, blue means overexpression.

Figure 2
Figure 2

mRNA expression of different ABCCs family members in LIHC patients and normal liver tissues. The mRNA expression of different ABCCs family members in LIHC patients from the TCGA database (A–M). ∗ P < .05, ∗∗ P < .01, ∗∗∗ P < .001, ∗∗∗∗ P < .0001.

Figure 3
Figure 3

Representative immunohistochemical images of different ABCCs family members in LIHC tissues and normal liver tissues (HPA database). The expression of ABCC3, ABCC4, ABCC8 and ABCC9 increased, and the expression of ABCC2 and ABCC12 decreased.

Figure 4
Figure 4

The relationship between the mRNA expression of ABCCs family members and the sex of LIHC patients. Box plots showed the mRNA expression (A–M) of family members of ABCCs in normal individuals and LIHC patients of different genders. ∗ P < .05; ∗∗ P < .01; ∗∗∗ P < .001, ∗∗∗∗ P < .0001.

Figure 5
Figure 5

The mRNA expression of ABCCs family members is correlated with the tumor grade of LIHC. The box plot showed the normal individuals or LIHC patients in Grade 1: Well differentiated (low grade), Grade 2: Moderately differentiated (intermediate grade), Grade 3: Poly differentiated (high grade) or Grade 4: Undifferentiated (high grade) (A–M) mRNA expression of ABCCs family members. ∗ P < .05; ∗∗ P < .01; ∗∗∗ P < .001, ∗∗∗∗ P < .0001.

Figure 6
Figure 6

The mRNA expression of ABCCs family members is correlated with the tumor stage of LIHC patients. The box plot shows the mRNA expression of ABCCs family members in normal individuals and LIHC patients in stage 1, stage 2, stage 3 and stage 4 (A–M). ∗ P < .05; ∗∗ P < .01; ∗∗∗ P < .001, ∗∗∗∗ P < .0001.

Figure 7
Figure 7

The mRNA expression of ABCCs family members is correlated with the status of lymph node metastasis in patients with LIHC. The box plot showed the mRNA expression of ABCCs family members in normal individuals or lymph node metastasis states N0 or N1 (A–M). ∗ P < .05; ∗∗ P < .01; ∗∗∗ P < .001, ∗∗∗∗ P < .0001.

Figure 8
Figure 8

Functional enrichment of members of the ABCCs family in LIHC. A. Analyze the network of ABCCs family members and their 20 related genes by GeneMANIA. B. GO enrichment analysis ranked the top 20 pathways; C. KEGG pathway analysis.

Figure 9
Figure 9

The relationship between the mRNA expression of ABCCs family members and the level of immune infiltration in LIHC. The mRNA expression of ABCCs family members were significantly correlated with the level of immune infiltration in LIHC (A–M).

Figure 10
Figure 10

The prognostic value of mRNA expression of ABBCs family members in LIHC patients. Compare the survival curves of high and low expression of ABBCs family members of LIHC patients in Kaplan–Meier plotter.

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References

    1. Kanwal F, Singal AG. Surveillance for hepatocellular carcinoma: current best practice and future direction. Gastroenterology 2019;157:54–64. - PMC - PubMed
    1. Gordan JD, Kennedy EB, Abou-Alfa GK, et al. . Systemic therapy for advanced hepatocellular carcinoma: ASCO guideline. J Clin Oncol 2020;38:4317–45. - PubMed
    1. Chen LT, Martinelli E, Cheng AL, et al. . Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with intermediate and advanced/relapsed hepatocellular carcinoma: a TOS-ESMO initiative endorsed by CSCO, ISMPO, JSMO, KSMO, MOS and SSO. Ann Oncol 2020;31:334–51. - PubMed
    1. Wan L, Guo L, Hu Y, et al. . Comparing the diagnostic value of serum oligosaccharide chain (G-test) and alpha-fetoprotein for hepatitis B virus-related liver cancer. Clin Biochem 2021;89:44–50. (2.573). - PubMed
    1. Zhu J, Tang B, Lv X, et al. . Identifying apoptosis-related transcriptomic aberrations and revealing clinical relevance as diagnostic and prognostic biomarker in hepatocellular carcinoma. Front Oncol 2020;10:519180. - PMC - PubMed

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