Tumor and Peritoneum-Associated Macrophage Gene Signature as a Novel Molecular Biomarker in Gastric Cancer
A spectrum of immune states resulting from tumor resident macrophages and T-lymphocytes in the solid tumor microenvironment correlates with patient outcomes. We hypothesized that in gastric cancer (GC), macrophages in a polarized immunosuppressive transcriptional state would be prognostic of poor su...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/7/4117 |
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| author | Kevin M. Sullivan Haiqing Li Annie Yang Zhifang Zhang Ruben R. Munoz Kelly M. Mahuron Yate-Ching Yuan Isaac Benjamin Paz Daniel Von Hoff Haiyong Han Yuman Fong Yanghee Woo |
| author_facet | Kevin M. Sullivan Haiqing Li Annie Yang Zhifang Zhang Ruben R. Munoz Kelly M. Mahuron Yate-Ching Yuan Isaac Benjamin Paz Daniel Von Hoff Haiyong Han Yuman Fong Yanghee Woo |
| author_sort | Kevin M. Sullivan |
| collection | DOAJ |
| description | A spectrum of immune states resulting from tumor resident macrophages and T-lymphocytes in the solid tumor microenvironment correlates with patient outcomes. We hypothesized that in gastric cancer (GC), macrophages in a polarized immunosuppressive transcriptional state would be prognostic of poor survival. We derived transcriptomic signatures for M2 (M2<sub>TS</sub>, <i>MRC1</i>; <i>MS4A4A</i>; <i>CD36</i>; <i>CCL13</i>; <i>CCL18</i>; <i>CCL23</i>; <i>SLC38A6</i>; <i>FGL2</i>; <i>FN1</i>; <i>MAF</i>) and M1 (M1<sub>TS</sub>, <i>CCR7</i>; <i>IL2RA</i>; <i>CXCL11</i>; <i>CCL19</i>; <i>CXCL10</i>; <i>PLA1A</i>; <i>PTX3</i>) macrophages, and cytolytic T-lymphocytes (CTL<sub>TS</sub>, <i>GZMA</i>; <i>GZMB</i>; <i>GZMH</i>; <i>GZMM</i>; <i>PRF1</i>). Primary GC in a TCGA stomach cancer dataset was evaluated for signature expressions, and a log-rank test determined overall survival (OS) and the disease-free interval (DFI). In 341 TCGA GC entries, high M2<sub>TS</sub> expression was associated with histological types and later stages. Low M2<sub>TS</sub> expression was associated with significantly better 5-year OS and DFI. We validated M2<sub>TS</sub> in prospectively collected peritoneal fluid of a GC patient cohort (<i>n</i> = 28). Single-cell RNA sequencing was used for signature expression in <i>CD68</i><sup>+</sup><i>CD163</i><sup>+</sup> cells and the log-rank test compared OS. GC patients with high M2<sub>TS</sub> in <i>CD68</i><sup>+</sup><i>CD163</i><sup>+</sup> cells in their peritoneal fluid had significantly worse OS than those with low expression. Multivariate analyses confirmed M2<sub>TS</sub> was significantly and independently associated with survival. As an independent predictor of poor survival, M2<sub>TS</sub> may be prognostic in primary tumors and peritoneal fluid of GC patients. |
| first_indexed | 2024-04-24T10:42:31Z |
| format | Article |
| id | doaj.art-ad97411e680042f5906b7d7031e45a6e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-24T10:42:31Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ad97411e680042f5906b7d7031e45a6e2024-04-12T13:20:42ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-04-01257411710.3390/ijms25074117Tumor and Peritoneum-Associated Macrophage Gene Signature as a Novel Molecular Biomarker in Gastric CancerKevin M. Sullivan0Haiqing Li1Annie Yang2Zhifang Zhang3Ruben R. Munoz4Kelly M. Mahuron5Yate-Ching Yuan6Isaac Benjamin Paz7Daniel Von Hoff8Haiyong Han9Yuman Fong10Yanghee Woo11Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USAIntegrative Genome Core, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USADepartment of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USADepartment of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USAMolecular Medicine Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USADepartment of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USAIntegrative Genome Core, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USADepartment of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USAMolecular Medicine Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USAMolecular Medicine Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USADepartment of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USADepartment of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USAA spectrum of immune states resulting from tumor resident macrophages and T-lymphocytes in the solid tumor microenvironment correlates with patient outcomes. We hypothesized that in gastric cancer (GC), macrophages in a polarized immunosuppressive transcriptional state would be prognostic of poor survival. We derived transcriptomic signatures for M2 (M2<sub>TS</sub>, <i>MRC1</i>; <i>MS4A4A</i>; <i>CD36</i>; <i>CCL13</i>; <i>CCL18</i>; <i>CCL23</i>; <i>SLC38A6</i>; <i>FGL2</i>; <i>FN1</i>; <i>MAF</i>) and M1 (M1<sub>TS</sub>, <i>CCR7</i>; <i>IL2RA</i>; <i>CXCL11</i>; <i>CCL19</i>; <i>CXCL10</i>; <i>PLA1A</i>; <i>PTX3</i>) macrophages, and cytolytic T-lymphocytes (CTL<sub>TS</sub>, <i>GZMA</i>; <i>GZMB</i>; <i>GZMH</i>; <i>GZMM</i>; <i>PRF1</i>). Primary GC in a TCGA stomach cancer dataset was evaluated for signature expressions, and a log-rank test determined overall survival (OS) and the disease-free interval (DFI). In 341 TCGA GC entries, high M2<sub>TS</sub> expression was associated with histological types and later stages. Low M2<sub>TS</sub> expression was associated with significantly better 5-year OS and DFI. We validated M2<sub>TS</sub> in prospectively collected peritoneal fluid of a GC patient cohort (<i>n</i> = 28). Single-cell RNA sequencing was used for signature expression in <i>CD68</i><sup>+</sup><i>CD163</i><sup>+</sup> cells and the log-rank test compared OS. GC patients with high M2<sub>TS</sub> in <i>CD68</i><sup>+</sup><i>CD163</i><sup>+</sup> cells in their peritoneal fluid had significantly worse OS than those with low expression. Multivariate analyses confirmed M2<sub>TS</sub> was significantly and independently associated with survival. As an independent predictor of poor survival, M2<sub>TS</sub> may be prognostic in primary tumors and peritoneal fluid of GC patients.https://www.mdpi.com/1422-0067/25/7/4117gastric cancerperitoneal metastasesmacrophageliquid biopsybiomarker |
| spellingShingle | Kevin M. Sullivan Haiqing Li Annie Yang Zhifang Zhang Ruben R. Munoz Kelly M. Mahuron Yate-Ching Yuan Isaac Benjamin Paz Daniel Von Hoff Haiyong Han Yuman Fong Yanghee Woo Tumor and Peritoneum-Associated Macrophage Gene Signature as a Novel Molecular Biomarker in Gastric Cancer International Journal of Molecular Sciences gastric cancer peritoneal metastases macrophage liquid biopsy biomarker |
| title | Tumor and Peritoneum-Associated Macrophage Gene Signature as a Novel Molecular Biomarker in Gastric Cancer |
| title_full | Tumor and Peritoneum-Associated Macrophage Gene Signature as a Novel Molecular Biomarker in Gastric Cancer |
| title_fullStr | Tumor and Peritoneum-Associated Macrophage Gene Signature as a Novel Molecular Biomarker in Gastric Cancer |
| title_full_unstemmed | Tumor and Peritoneum-Associated Macrophage Gene Signature as a Novel Molecular Biomarker in Gastric Cancer |
| title_short | Tumor and Peritoneum-Associated Macrophage Gene Signature as a Novel Molecular Biomarker in Gastric Cancer |
| title_sort | tumor and peritoneum associated macrophage gene signature as a novel molecular biomarker in gastric cancer |
| topic | gastric cancer peritoneal metastases macrophage liquid biopsy biomarker |
| url | https://www.mdpi.com/1422-0067/25/7/4117 |
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