Prognostic value of SLC4A4 and its correlation with the microsatellite instability in colorectal cancer
ObjectiveTo explore new biomarkers related to microsatellite instability in order to better predict prognosis and guide medication.MethodsThe “limma” R package was used to identify differentially expressed genes in GSE24514, and then weighted correlation network analysis was used to select key genes...
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| Format: | Article |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1179120/full |
| _version_ | 1797844298633314304 |
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| author | Shaorui Rui Dong Wang Yong Huang Jingyun Xu Hailang Zhou Hailang Zhou Hesong Zhang |
| author_facet | Shaorui Rui Dong Wang Yong Huang Jingyun Xu Hailang Zhou Hailang Zhou Hesong Zhang |
| author_sort | Shaorui Rui |
| collection | DOAJ |
| description | ObjectiveTo explore new biomarkers related to microsatellite instability in order to better predict prognosis and guide medication.MethodsThe “limma” R package was used to identify differentially expressed genes in GSE24514, and then weighted correlation network analysis was used to select key genes. Different cell types in the tumor microenvironment were identified and analyzed by single-cell sequencing, with a Lasso regression model used to screen prognostic variables. Furthermore, the correlation between microsatellite instability and potential prognostic variables was explored, as well as the expression characteristics and clinical characteristics of the prognostic variables in the TCGA, UALCAN, and HPA databases. PCR assay was used to investigate the expression of SLC4A4 in colorectal cancer cell lines. Finally, we further verified the expression of SLC4A4 by immunohistochemistry.ResultsFirst, 844 differentially expressed genes in GSE24514 were identified. Subsequently, weighted co-expression network analysis (WGCNA) of GSE24514 obtained all the genes significantly associated with microsatellite instability (MSI), a total of 1452. Analysis of GSE166555 single cell sequencing data set yielded 1564 differentially expressed genes. The gene sets obtained from the above three analysis processes were intersected, and 174 genes were finally obtained. The Lasso regression model revealed two potential prognostic genes, TIMP1 and SLC4A4, of which, there was a stronger correlation between microsatellite instability and SLC4A4. The mRNA and protein expression of SLC4A4 was significantly decreased in tumors, and patients with low SLC4A4 expression had a poor prognosis. In addition, SLC4A4 was specifically expressed in epithelial cells. In the microenvironment of colorectal cancer, malignant cells have a strong interaction with different stromal cells. PCR showed that SLC4A4 was significantly down-regulated in colorectal cancer cell lines Caco-2, HCT116 and HT29 compared with normal control NCM460 cell lines. Immunohistochemistry also showed low expression of SLC4A4 in colorectal cancer.ConclusionSLC4A4, as a tumor suppressor gene, is significantly downregulated and positively correlated with microsatellite instability, thus it may be combined with microsatellite instability to guide colorectal cancer treatment. |
| first_indexed | 2024-04-09T17:20:01Z |
| format | Article |
| id | doaj.art-f1cc28702f024e609db820d5afca0d7b |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-09T17:20:01Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-f1cc28702f024e609db820d5afca0d7b2023-04-19T05:14:50ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-04-011310.3389/fonc.2023.11791201179120Prognostic value of SLC4A4 and its correlation with the microsatellite instability in colorectal cancerShaorui Rui0Dong Wang1Yong Huang2Jingyun Xu3Hailang Zhou4Hailang Zhou5Hesong Zhang6Department of General Surgery, The Second Affiliated Hospital of Wannan Medical College, Wuhu, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu, ChinaDepartment of General Surgery, The Second Affiliated Hospital of Wannan Medical College, Wuhu, ChinaSchool of Basic Medicine, Wannan Medical College, Wuhu, ChinaDepartment of Gastroenterology, Lianshui People’s Hospital Affiliated to Kangda College of Nanjing Medical University, Huai’an, ChinaThe Institute of Life Sciences, Jiangsu College of Nursing, Huai’an, ChinaDepartment of Hepatobiliary Surgery, The Second People’s Hospital of Wuhu, Wuhu, ChinaObjectiveTo explore new biomarkers related to microsatellite instability in order to better predict prognosis and guide medication.MethodsThe “limma” R package was used to identify differentially expressed genes in GSE24514, and then weighted correlation network analysis was used to select key genes. Different cell types in the tumor microenvironment were identified and analyzed by single-cell sequencing, with a Lasso regression model used to screen prognostic variables. Furthermore, the correlation between microsatellite instability and potential prognostic variables was explored, as well as the expression characteristics and clinical characteristics of the prognostic variables in the TCGA, UALCAN, and HPA databases. PCR assay was used to investigate the expression of SLC4A4 in colorectal cancer cell lines. Finally, we further verified the expression of SLC4A4 by immunohistochemistry.ResultsFirst, 844 differentially expressed genes in GSE24514 were identified. Subsequently, weighted co-expression network analysis (WGCNA) of GSE24514 obtained all the genes significantly associated with microsatellite instability (MSI), a total of 1452. Analysis of GSE166555 single cell sequencing data set yielded 1564 differentially expressed genes. The gene sets obtained from the above three analysis processes were intersected, and 174 genes were finally obtained. The Lasso regression model revealed two potential prognostic genes, TIMP1 and SLC4A4, of which, there was a stronger correlation between microsatellite instability and SLC4A4. The mRNA and protein expression of SLC4A4 was significantly decreased in tumors, and patients with low SLC4A4 expression had a poor prognosis. In addition, SLC4A4 was specifically expressed in epithelial cells. In the microenvironment of colorectal cancer, malignant cells have a strong interaction with different stromal cells. PCR showed that SLC4A4 was significantly down-regulated in colorectal cancer cell lines Caco-2, HCT116 and HT29 compared with normal control NCM460 cell lines. Immunohistochemistry also showed low expression of SLC4A4 in colorectal cancer.ConclusionSLC4A4, as a tumor suppressor gene, is significantly downregulated and positively correlated with microsatellite instability, thus it may be combined with microsatellite instability to guide colorectal cancer treatment.https://www.frontiersin.org/articles/10.3389/fonc.2023.1179120/fullmicrosatellite instabilitysingle-cell sequencingcolorectal cancerbiomarkerSlc4a4 |
| spellingShingle | Shaorui Rui Dong Wang Yong Huang Jingyun Xu Hailang Zhou Hailang Zhou Hesong Zhang Prognostic value of SLC4A4 and its correlation with the microsatellite instability in colorectal cancer Frontiers in Oncology microsatellite instability single-cell sequencing colorectal cancer biomarker Slc4a4 |
| title | Prognostic value of SLC4A4 and its correlation with the microsatellite instability in colorectal cancer |
| title_full | Prognostic value of SLC4A4 and its correlation with the microsatellite instability in colorectal cancer |
| title_fullStr | Prognostic value of SLC4A4 and its correlation with the microsatellite instability in colorectal cancer |
| title_full_unstemmed | Prognostic value of SLC4A4 and its correlation with the microsatellite instability in colorectal cancer |
| title_short | Prognostic value of SLC4A4 and its correlation with the microsatellite instability in colorectal cancer |
| title_sort | prognostic value of slc4a4 and its correlation with the microsatellite instability in colorectal cancer |
| topic | microsatellite instability single-cell sequencing colorectal cancer biomarker Slc4a4 |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1179120/full |
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