CLEC4E upregulation in gastric cancer: A potential therapeutic target correlating with tumor-associated macrophages
Background: CLEC4E has been reported to promote lung cancer progression. Tumor-associated macrophages (TAMs) play an important role in tumorigenesis. Whether the expression of CLEC4E in TAMs is associated with gastric carcinogenesis remains unclear. Methods: The TIMER, UALCAN, UCSC Xena, and KM plot...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024032031 |
| _version_ | 1797259810366816256 |
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| author | Qin Jiang Dan Xiao Ao Wang Qiong Yu Ying Yin Jingchong Wu Yan Zhang Tian Jin Baicheng Kuang Yegui Jia |
| author_facet | Qin Jiang Dan Xiao Ao Wang Qiong Yu Ying Yin Jingchong Wu Yan Zhang Tian Jin Baicheng Kuang Yegui Jia |
| author_sort | Qin Jiang |
| collection | DOAJ |
| description | Background: CLEC4E has been reported to promote lung cancer progression. Tumor-associated macrophages (TAMs) play an important role in tumorigenesis. Whether the expression of CLEC4E in TAMs is associated with gastric carcinogenesis remains unclear. Methods: The TIMER, UALCAN, UCSC Xena, and KM plotter databases are used to examine the expression of CLEC4E and its prognostic significance in gastric cancer (GC). Additionally, GO, KEGG, and GSEA analysis were conducted, and single-cell RNA-seq (scRNA-seq) datasets were utilized. The Coremine medical database was used to predict therapeutic drugs, and molecular docking was performed. Human GC samples were obtained, and co-culture models were constructed to evaluate the effects of CLEC4E in TAMs on tumor growth, migration, and invasion in vitro. Results: CLEC4E was significantly upregulated in GC, and high CLEC4E expression was associated with poor prognosis. Western blotting and immunostaining showed increased protein levels of CLEC4E in GC. GO, KEGG, and GSEA results indicated that CLEC4E is involved in immune response. Immune infiltration analysis demonstrated that CLEC4E expression positively correlated with multiple immune cell types. scRNA-seq analyses revealed that CLEC4E was predominantly expressed in myeloid cells specifically TAMs, in GC. In vitro experiments confirmed that MFC induced CLEC4E expression in TAMs to mediate tumor progression. Specifically targeting CLEC4E by si-CLEC4E or stigmasterol inhibited cancer cell migration and invasion. Conclusion: CLEC4E is a potential prognostic biomarker and new therapeutic target for GC that can be specifically targeted by stigmasterol. |
| first_indexed | 2024-03-07T16:53:23Z |
| format | Article |
| id | doaj.art-c1eb7c009a25414b8217f41292397048 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-24T23:15:21Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-c1eb7c009a25414b8217f412923970482024-03-17T07:57:33ZengElsevierHeliyon2405-84402024-03-01105e27172CLEC4E upregulation in gastric cancer: A potential therapeutic target correlating with tumor-associated macrophagesQin Jiang0Dan Xiao1Ao Wang2Qiong Yu3Ying Yin4Jingchong Wu5Yan Zhang6Tian Jin7Baicheng Kuang8Yegui Jia9Department of Gastroenterology, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, 430000, ChinaDepartment of Gastroenterology, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, 430000, ChinaDepartment of Gastroenterology, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, 430000, ChinaDepartment of Gastroenterology, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, 430000, ChinaDepartment of Gastroenterology, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, 430000, ChinaDepartment of Gastroenterology, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, 430000, ChinaDepartment of Gastroenterology, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, 430000, ChinaDepartment of Pathology, Hanchuan People's Hospital, Hanchuan, 431600, ChinaInstitute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Corresponding author.Department of Gastroenterology, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, 430000, China; Corresponding author.Background: CLEC4E has been reported to promote lung cancer progression. Tumor-associated macrophages (TAMs) play an important role in tumorigenesis. Whether the expression of CLEC4E in TAMs is associated with gastric carcinogenesis remains unclear. Methods: The TIMER, UALCAN, UCSC Xena, and KM plotter databases are used to examine the expression of CLEC4E and its prognostic significance in gastric cancer (GC). Additionally, GO, KEGG, and GSEA analysis were conducted, and single-cell RNA-seq (scRNA-seq) datasets were utilized. The Coremine medical database was used to predict therapeutic drugs, and molecular docking was performed. Human GC samples were obtained, and co-culture models were constructed to evaluate the effects of CLEC4E in TAMs on tumor growth, migration, and invasion in vitro. Results: CLEC4E was significantly upregulated in GC, and high CLEC4E expression was associated with poor prognosis. Western blotting and immunostaining showed increased protein levels of CLEC4E in GC. GO, KEGG, and GSEA results indicated that CLEC4E is involved in immune response. Immune infiltration analysis demonstrated that CLEC4E expression positively correlated with multiple immune cell types. scRNA-seq analyses revealed that CLEC4E was predominantly expressed in myeloid cells specifically TAMs, in GC. In vitro experiments confirmed that MFC induced CLEC4E expression in TAMs to mediate tumor progression. Specifically targeting CLEC4E by si-CLEC4E or stigmasterol inhibited cancer cell migration and invasion. Conclusion: CLEC4E is a potential prognostic biomarker and new therapeutic target for GC that can be specifically targeted by stigmasterol.http://www.sciencedirect.com/science/article/pii/S2405844024032031CLEC4EGastric cancerTumor-associated macrophagesStigmasterol |
| spellingShingle | Qin Jiang Dan Xiao Ao Wang Qiong Yu Ying Yin Jingchong Wu Yan Zhang Tian Jin Baicheng Kuang Yegui Jia CLEC4E upregulation in gastric cancer: A potential therapeutic target correlating with tumor-associated macrophages Heliyon CLEC4E Gastric cancer Tumor-associated macrophages Stigmasterol |
| title | CLEC4E upregulation in gastric cancer: A potential therapeutic target correlating with tumor-associated macrophages |
| title_full | CLEC4E upregulation in gastric cancer: A potential therapeutic target correlating with tumor-associated macrophages |
| title_fullStr | CLEC4E upregulation in gastric cancer: A potential therapeutic target correlating with tumor-associated macrophages |
| title_full_unstemmed | CLEC4E upregulation in gastric cancer: A potential therapeutic target correlating with tumor-associated macrophages |
| title_short | CLEC4E upregulation in gastric cancer: A potential therapeutic target correlating with tumor-associated macrophages |
| title_sort | clec4e upregulation in gastric cancer a potential therapeutic target correlating with tumor associated macrophages |
| topic | CLEC4E Gastric cancer Tumor-associated macrophages Stigmasterol |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024032031 |
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