Cancer Stem Cell Marker DCLK1 Correlates with Tumorigenic Immune Infiltrates in the Colon and Gastric Adenocarcinoma Microenvironments
Immunotherapy that has proven efficacy in several solid cancers plays a partial role in improving clinical outcomes of advanced gastrointestinal (GI) cancers. There is an unmet need to find new immune-related therapeutic targets. Doublecortin-like kinase 1 (DCLK1) marks tuft cells which are recogniz...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/2/274 |
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| author | Xiangyan Wu Dongfeng Qu Nathaniel Weygant Jun Peng Courtney W. Houchen |
| author_facet | Xiangyan Wu Dongfeng Qu Nathaniel Weygant Jun Peng Courtney W. Houchen |
| author_sort | Xiangyan Wu |
| collection | DOAJ |
| description | Immunotherapy that has proven efficacy in several solid cancers plays a partial role in improving clinical outcomes of advanced gastrointestinal (GI) cancers. There is an unmet need to find new immune-related therapeutic targets. Doublecortin-like kinase 1 (DCLK1) marks tuft cells which are recognized as cancer-initiating cells and regulators of the type II immune response, and has been studied for its role in many cancers including colon and gastric cancers, but its role in tumor immunity remains unexplored. In the current study, we analyzed colon and gastric cancer RNA sequencing data from 283 and 415 patients, respectively, from The Cancer Genome Atlas (TCGA). High DCLK1 expression predicted the worse clinical outcomes in colon and gastric cancer patients and correlated with increased immune and stromal components. Further analysis indicated that DCLK1 was strongly linked to infiltration of multiple immune cell types, especially TAMs and Treg, and strongly correlated with increased CD8+ T cell inhibitors TGFB1 and CXCL12 and their receptors, suggesting it may contribute to TAM-mediated inhibition of CD8+ T cells. Interestingly, we found that DCLK1 was a prognostic biomarker in left-sided colon cancer, which has worse outcomes and demonstrates a reduced response to existing immunotherapies. In conclusion, our results demonstrate that DCLK1 is linked with functional regulation of the tumor microenvironment and may have potential as a prognostic biomarker and adjuvant target to promote immunotherapy sensitivity in colon and gastric cancer patients. |
| first_indexed | 2024-03-12T20:14:50Z |
| format | Article |
| id | doaj.art-a72121cb11254edab157c65a4800a26c |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T20:14:50Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-a72121cb11254edab157c65a4800a26c2023-08-02T01:26:56ZengMDPI AGCancers2072-66942020-01-0112227410.3390/cancers12020274cancers12020274Cancer Stem Cell Marker DCLK1 Correlates with Tumorigenic Immune Infiltrates in the Colon and Gastric Adenocarcinoma MicroenvironmentsXiangyan Wu0Dongfeng Qu1Nathaniel Weygant2Jun Peng3Courtney W. Houchen4Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAAcademy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, ChinaAcademy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, ChinaDepartment of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAImmunotherapy that has proven efficacy in several solid cancers plays a partial role in improving clinical outcomes of advanced gastrointestinal (GI) cancers. There is an unmet need to find new immune-related therapeutic targets. Doublecortin-like kinase 1 (DCLK1) marks tuft cells which are recognized as cancer-initiating cells and regulators of the type II immune response, and has been studied for its role in many cancers including colon and gastric cancers, but its role in tumor immunity remains unexplored. In the current study, we analyzed colon and gastric cancer RNA sequencing data from 283 and 415 patients, respectively, from The Cancer Genome Atlas (TCGA). High DCLK1 expression predicted the worse clinical outcomes in colon and gastric cancer patients and correlated with increased immune and stromal components. Further analysis indicated that DCLK1 was strongly linked to infiltration of multiple immune cell types, especially TAMs and Treg, and strongly correlated with increased CD8+ T cell inhibitors TGFB1 and CXCL12 and their receptors, suggesting it may contribute to TAM-mediated inhibition of CD8+ T cells. Interestingly, we found that DCLK1 was a prognostic biomarker in left-sided colon cancer, which has worse outcomes and demonstrates a reduced response to existing immunotherapies. In conclusion, our results demonstrate that DCLK1 is linked with functional regulation of the tumor microenvironment and may have potential as a prognostic biomarker and adjuvant target to promote immunotherapy sensitivity in colon and gastric cancer patients.https://www.mdpi.com/2072-6694/12/2/274tumor immunitygi cancerdclk1biomarker and adjuvant targets |
| spellingShingle | Xiangyan Wu Dongfeng Qu Nathaniel Weygant Jun Peng Courtney W. Houchen Cancer Stem Cell Marker DCLK1 Correlates with Tumorigenic Immune Infiltrates in the Colon and Gastric Adenocarcinoma Microenvironments Cancers tumor immunity gi cancer dclk1 biomarker and adjuvant targets |
| title | Cancer Stem Cell Marker DCLK1 Correlates with Tumorigenic Immune Infiltrates in the Colon and Gastric Adenocarcinoma Microenvironments |
| title_full | Cancer Stem Cell Marker DCLK1 Correlates with Tumorigenic Immune Infiltrates in the Colon and Gastric Adenocarcinoma Microenvironments |
| title_fullStr | Cancer Stem Cell Marker DCLK1 Correlates with Tumorigenic Immune Infiltrates in the Colon and Gastric Adenocarcinoma Microenvironments |
| title_full_unstemmed | Cancer Stem Cell Marker DCLK1 Correlates with Tumorigenic Immune Infiltrates in the Colon and Gastric Adenocarcinoma Microenvironments |
| title_short | Cancer Stem Cell Marker DCLK1 Correlates with Tumorigenic Immune Infiltrates in the Colon and Gastric Adenocarcinoma Microenvironments |
| title_sort | cancer stem cell marker dclk1 correlates with tumorigenic immune infiltrates in the colon and gastric adenocarcinoma microenvironments |
| topic | tumor immunity gi cancer dclk1 biomarker and adjuvant targets |
| url | https://www.mdpi.com/2072-6694/12/2/274 |
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