Identification of Hub Genes and Biological Mechanisms Associated with Non-Alcoholic Fatty Liver Disease and Triple-Negative Breast Cancer
The relationship between non-alcoholic fatty liver disease (NAFLD) and triple-negative breast cancer (TNBC) has been widely recognized, but the underlying mechanisms are still unknown. The objective of this study was to identify the hub genes associated with NAFLD and TNBC, and to explore the potent...
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MDPI AG
2023-04-01
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| author | Jingjin Zhu Ningning Min Wenye Gong Yizhu Chen Xiru Li |
| author_facet | Jingjin Zhu Ningning Min Wenye Gong Yizhu Chen Xiru Li |
| author_sort | Jingjin Zhu |
| collection | DOAJ |
| description | The relationship between non-alcoholic fatty liver disease (NAFLD) and triple-negative breast cancer (TNBC) has been widely recognized, but the underlying mechanisms are still unknown. The objective of this study was to identify the hub genes associated with NAFLD and TNBC, and to explore the potential co-pathogenesis and prognostic linkage of these two diseases. We used GEO, TCGA, STRING, ssGSEA, and Rstudio to investigate the common differentially expressed genes (DEGs), conduct functional and signaling pathway enrichment analyses, and determine prognostic value between TNBC and NAFLD. GO and KEGG enrichment analyses of the common DEGs showed that they were enriched in leukocyte aggregation, migration and adhesion, apoptosis regulation, and the PPAR signaling pathway. Fourteen candidate hub genes most likely to mediate NAFLD and TNBC occurrence were identified and validation results in a new cohort showed that ITGB2, RAC2, ITGAM, and CYBA were upregulated in both diseases. A univariate Cox analysis suggested that high expression levels of ITGB2, RAC2, ITGAM, and CXCL10 were associated with a good prognosis in TNBC. Immune infiltration analysis of TNBC samples showed that NCF2, ICAM1, and CXCL10 were significantly associated with activated CD8 T cells and activated CD4 T cells. NCF2, CXCL10, and CYBB were correlated with regulatory T cells and myeloid-derived suppressor cells. This study demonstrated that the redox reactions regulated by the NADPH oxidase (NOX) subunit genes and the transport and activation of immune cells regulated by integrins may play a central role in the co-occurrence trend of NAFLD and TNBC. Additionally, ITGB2, RAC2, and ITGAM were upregulated in both diseases and were prognostic protective factors of TNBC; they may be potential therapeutic targets for treatment of TNBC patients with NAFLD, but further experimental studies are still needed. |
| first_indexed | 2024-03-11T04:50:21Z |
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| language | English |
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| spelling | doaj.art-be2e212b3e454d24a688372cfbf147f02023-11-17T20:06:39ZengMDPI AGLife2075-17292023-04-0113499810.3390/life13040998Identification of Hub Genes and Biological Mechanisms Associated with Non-Alcoholic Fatty Liver Disease and Triple-Negative Breast CancerJingjin Zhu0Ningning Min1Wenye Gong2Yizhu Chen3Xiru Li4School of Medicine, Nankai University, Tianjin 300071, ChinaSchool of Medicine, Nankai University, Tianjin 300071, ChinaDepartment of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, ChinaDepartment of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, ChinaDepartment of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, ChinaThe relationship between non-alcoholic fatty liver disease (NAFLD) and triple-negative breast cancer (TNBC) has been widely recognized, but the underlying mechanisms are still unknown. The objective of this study was to identify the hub genes associated with NAFLD and TNBC, and to explore the potential co-pathogenesis and prognostic linkage of these two diseases. We used GEO, TCGA, STRING, ssGSEA, and Rstudio to investigate the common differentially expressed genes (DEGs), conduct functional and signaling pathway enrichment analyses, and determine prognostic value between TNBC and NAFLD. GO and KEGG enrichment analyses of the common DEGs showed that they were enriched in leukocyte aggregation, migration and adhesion, apoptosis regulation, and the PPAR signaling pathway. Fourteen candidate hub genes most likely to mediate NAFLD and TNBC occurrence were identified and validation results in a new cohort showed that ITGB2, RAC2, ITGAM, and CYBA were upregulated in both diseases. A univariate Cox analysis suggested that high expression levels of ITGB2, RAC2, ITGAM, and CXCL10 were associated with a good prognosis in TNBC. Immune infiltration analysis of TNBC samples showed that NCF2, ICAM1, and CXCL10 were significantly associated with activated CD8 T cells and activated CD4 T cells. NCF2, CXCL10, and CYBB were correlated with regulatory T cells and myeloid-derived suppressor cells. This study demonstrated that the redox reactions regulated by the NADPH oxidase (NOX) subunit genes and the transport and activation of immune cells regulated by integrins may play a central role in the co-occurrence trend of NAFLD and TNBC. Additionally, ITGB2, RAC2, and ITGAM were upregulated in both diseases and were prognostic protective factors of TNBC; they may be potential therapeutic targets for treatment of TNBC patients with NAFLD, but further experimental studies are still needed.https://www.mdpi.com/2075-1729/13/4/998triple-negative breast cancer (TNBC)non-alcoholic fatty liver disease (NAFLD)non-alcoholic steatohepatitis (NASH)bioinformatics analysishub genesprognostic value |
| spellingShingle | Jingjin Zhu Ningning Min Wenye Gong Yizhu Chen Xiru Li Identification of Hub Genes and Biological Mechanisms Associated with Non-Alcoholic Fatty Liver Disease and Triple-Negative Breast Cancer Life triple-negative breast cancer (TNBC) non-alcoholic fatty liver disease (NAFLD) non-alcoholic steatohepatitis (NASH) bioinformatics analysis hub genes prognostic value |
| title | Identification of Hub Genes and Biological Mechanisms Associated with Non-Alcoholic Fatty Liver Disease and Triple-Negative Breast Cancer |
| title_full | Identification of Hub Genes and Biological Mechanisms Associated with Non-Alcoholic Fatty Liver Disease and Triple-Negative Breast Cancer |
| title_fullStr | Identification of Hub Genes and Biological Mechanisms Associated with Non-Alcoholic Fatty Liver Disease and Triple-Negative Breast Cancer |
| title_full_unstemmed | Identification of Hub Genes and Biological Mechanisms Associated with Non-Alcoholic Fatty Liver Disease and Triple-Negative Breast Cancer |
| title_short | Identification of Hub Genes and Biological Mechanisms Associated with Non-Alcoholic Fatty Liver Disease and Triple-Negative Breast Cancer |
| title_sort | identification of hub genes and biological mechanisms associated with non alcoholic fatty liver disease and triple negative breast cancer |
| topic | triple-negative breast cancer (TNBC) non-alcoholic fatty liver disease (NAFLD) non-alcoholic steatohepatitis (NASH) bioinformatics analysis hub genes prognostic value |
| url | https://www.mdpi.com/2075-1729/13/4/998 |
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