Clinical value and transcriptional regulatory mechanism of ABCA7 in colorectal cancer

doi:10.3969/j.issn.1674-8115.2025.11.008

Abstract

Abstract:

Objective ·To investigate the prognostic value of the ATP-binding cassette subfamily A member 7 (ABCA7) gene in colorectal cancer (CRC) and provide a novel molecular marker for the precise diagnosis and personalized treatment of CRC. Methods ·Single-cell transcriptome data of CRC were retrieved from the Tumor Immune Single-cell Hub (TISCH). Spatial transcriptome data of sample GSM8594571 (based on the 10x Genomics Visium platform) were downloaded from the Gene Expression Omnibus (GEO) database. Transcriptome data from the TCGA-COAD and TCGA-READ projects were extracted from The Cancer Genome Atlas (TCGA) database. Using a multi-omics integration analysis strategy, single-cell transcriptome data were employed to analyze the expression patterns of ABCA7 in different cell subpopulations and were combined with spatial transcriptome data to explore its spatial distribution characteristics in tumor and adjacent tissues. The Cox Proportional Hazards Model (Cox) was used to evaluate the prognostic value of ABCA7. The effect of ABCA7 on CRC cell proliferation was verified using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) knockout technology combined with the CERES algorithm. The transcriptional regulatory network between ABCA7 and the transcription factors zinc finger BTB domain-containing protein 33 (ZBTB33) and Nuclear factor-κB-repressing factor (NKRF) was constructed using chromatin immunoprecipitation sequencing (ChIP-seq) data from the Cistrome database and Pearson correlation analysis. Results ·The analysis revealed that ABCA7 was significantly overexpressed in CRC malignant cells, with further upregulation particularly in tumor tissues with high Ki-67 expression. Moreover, the mRNA expression of ABCA7 in tumor tissues was significantly higher than that in normal tissues (P<0.05), showing certain diagnostic efficacy [area under the curve (AUC) of the receiver operating characteristic (ROC) curve=0.686]. Knockout of ABCA7 significantly inhibited the proliferative capacity of CRC cell lines (e.g., C75, CL11). Patients in the ABCA7 high-expression group had significantly shorter overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) (all P<0.05). Epigenetic analysis showed that ZBTB33 and NKRF could directly bind to the regulatory region of the ABCA7 gene, forming a ZBTB33/NKRF-ABCA7 transcriptional regulatory axis, and all three were significantly upregulated in CRC (P<0.05). Conclusion ·ABCA7 is highly expressed in CRC and associated with poor prognosis. The ZBTB33/NKRF-ABCA7 regulatory axis may be a key mechanism driving CRC progression.

Key words: ATP-binding cassette subfamily A member 7 (ABCA7), colorectal cancer, spatial transcriptomics, single-cell sequencing, CRISPR technology, epigenetics, transcriptional regulatory axis

CLC Number:

R735.3

SUN Ruizhuang, QIAO Kunpeng, LI Pu, XU Xiaolian, MENG Jun. Clinical value and transcriptional regulatory mechanism of ABCA7 in colorectal cancer[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(11): 1490-1501.

Figures/Tables 7

Fig 1 Single-cell sequencing data of ABCA7 showing the expression distribution of ABCA7 in malignant cells of CRC

Fig 2 Spatial transcriptome showing the expression distribution of ABCA7 in active tissue cells of CRC

Fig 3 mRNA expression level of ABCA7 in CRC and its effect on CRC cell growth

Fig 4 Immunohistochemical staining images of ABCA7 in normal and tumor tissues of CRC

Fig 5 mRNA expression level of ABCA7 in CRC and its correlation with prognosis

Fig 6 Co-expression analysis of ABCA7 with highly expressed ZBTB33 and NKRF in CRC

Fig 7 Epigenetic regulation of ABCA7 on highly expressed ZBTB33 and NKRF in CRC and analysis of gene network

TrendMD

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