Identification of ATP8B1 as a Tumor Suppressor Gene for Colorectal Cancer and Its Involvement in Phospholipid Homeostasis
| Autor: | Li Deng, Geng-Ming Niu, Jun Ren, Chong-Wei Ke, Luis Loura |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Article Subject General Immunology and Microbiology Tumor suppressor gene business.industry Colorectal cancer General Medicine Flippase Phospholipid transport medicine.disease_cause medicine.disease General Biochemistry Genetics and Molecular Biology Transcriptome 03 medical and health sciences 030104 developmental biology 0302 clinical medicine 030220 oncology & carcinogenesis Cancer research medicine Phospholipid homeostasis Medicine Phospholipid metabolic process Carcinogenesis business |
| Zdroj: | BioMed Research International, Vol 2020 (2020) |
| ISSN: | 2314-6141 2314-6133 |
| DOI: | 10.1155/2020/2015648 |
| Popis: | Homeostasis of membrane phospholipids plays an important role in cell oncogenesis and cancer progression. The flippase ATPase class I type 8b member 1 (ATP8B1), one of the P4-ATPases, translocates specific phospholipids from the exoplasmic to the cytoplasmic leaflet of membranes. ATP8B1 is critical for maintaining the epithelium membrane stability and polarity. However, the prognostic values of ATP8B1 in colorectal cancer (CRC) patients remain unclear. We analyzed transcriptomics, genomics, and clinical data of CRC samples from The Cancer Genome Atlas (TCGA). ATP8B1 was the only potential biomarker of phospholipid transporters in CRC. Its prognostic value was also validated with the data from the Gene Expression Omnibus (GEO). Compared to the normal group, the expression of ATP8B1 was downregulated in the tumor group and the CRC cell lines, which declined with disease progression. The lower expression level of ATP8B1 was also significantly associated with worse survival outcomes in both the discovery samples (359 patients) and the validation samples (566 patients). In multivariate analyses, low ATP8B1 levels predicted unfavorable OS (adjusted HR 1.512, 95% CI: 1.069-2.137; P = 0.019 ) and were associated with poor progress-free interval (PFI) (adjusted HR: 1.62, 95% CI: 1.207-2.174; P = 0.001 ). The pathway analysis results showed that the underexpression of ATP8B1 was negatively associated with phospholipid transport, phospholipid metabolic process, and cell-cell adherent junction and positively associated with the epithelial-mesenchymal transition in CRC. Our analysis suggests that ATP8B1 is a potential cancer suppressor in CRC patients and may offer new strategies for CRC therapy. |
| Databáze: | OpenAIRE |
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