SECTM1 acts as an immune-related biomarker of poor prognosis and promotes cancer progression by modulating M2 macrophage polarization in esophageal squamous cell carcinoma
Esophageal squamous cell carcinoma (ESCC) is the most prevalent primary malignant esophageal tumor in China and has a poor prognosis, but lacks effective diagnostic and prognostic biomarkers. Through single-sample gene set enrichment analysis (ssGSEA), we conducted immune genomic analysis based on 2...
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Frontiers Media S.A.
2025-01-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1507227/full |
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author | Pengzhou Kong Pengzhou Kong Pengzhou Kong Ye Jiao Ye Jiao Meng Sun Meng Sun Zhinan Zhou Zhinan Zhou Yingying Zhang Yingying Zhang Xin Yang Xin Yang Jing Ren Jing Ren Mengyuan Yang Mengyuan Yang Yanyan Dong Yanyan Dong Yanyan Dong Bin Song |
author_facet | Pengzhou Kong Pengzhou Kong Pengzhou Kong Ye Jiao Ye Jiao Meng Sun Meng Sun Zhinan Zhou Zhinan Zhou Yingying Zhang Yingying Zhang Xin Yang Xin Yang Jing Ren Jing Ren Mengyuan Yang Mengyuan Yang Yanyan Dong Yanyan Dong Yanyan Dong Bin Song |
author_sort | Pengzhou Kong |
collection | DOAJ |
description | Esophageal squamous cell carcinoma (ESCC) is the most prevalent primary malignant esophageal tumor in China and has a poor prognosis, but lacks effective diagnostic and prognostic biomarkers. Through single-sample gene set enrichment analysis (ssGSEA), we conducted immune genomic analysis based on 28 immune features using transcriptomic data from 155 ESCC cases. We established of two ESCC subtypes characterized by high and low immune profiles, and 352 differentially expressed immune genes were identified between the two subtypes. Performed with univariate and multivariate Cox regression, a novel prognostic prediction model was developed based on three immune-related genes (MAP3K8, SECTM1, IGLV7-43), which has been identified as a relatively accurate, independent, and specific prognostic risk model for ESCC patients in different ESCC cohorts. Furthermore, SECTM1 was upregulated in ESCC tissues and associated with adverse clinical outcomes. In cell experiments, overexpression of SECTM1 effectively promoted the proliferation, migration, and invasion of ESCC cells, while SECTM1 knockdown significantly inhibited these cellular processes. Furthermore, its overexpression promoted macrophage polarization towards the M2-like phenotype and promoted the migration of M2-like macrophage cells and C-C Motif Chemokine Ligand 5 (CCL5) was the key mediator in the pro-cancer effect of SECTM1. In a Conclusion, our study established a prognostic prediction model based on immune-related gene signature, which provided a reliable prognostic tool for ESCC and identified SECTM1 as a potential biomarker in ESCC. |
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language | English |
publishDate | 2025-01-01 |
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spelling | doaj-art-fb35fe2f86db4e4a9b004790a0aa2cd52025-01-29T06:46:00ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.15072271507227SECTM1 acts as an immune-related biomarker of poor prognosis and promotes cancer progression by modulating M2 macrophage polarization in esophageal squamous cell carcinomaPengzhou Kong0Pengzhou Kong1Pengzhou Kong2Ye Jiao3Ye Jiao4Meng Sun5Meng Sun6Zhinan Zhou7Zhinan Zhou8Yingying Zhang9Yingying Zhang10Xin Yang11Xin Yang12Jing Ren13Jing Ren14Mengyuan Yang15Mengyuan Yang16Yanyan Dong17Yanyan Dong18Yanyan Dong19Bin Song20Translational Medicine Research Center and Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaKey Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaState Key Laboratory for Pneumoconiosis of National Health Commission, Key Laboratory of Prevention, Treatment and Fundamental Studies for Respiratory Diseases of Shanxi, Department of Respiratory and Critical Care Medicine, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, ChinaTranslational Medicine Research Center and Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaKey Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaTranslational Medicine Research Center and Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaKey Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaTranslational Medicine Research Center and Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaKey Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaTranslational Medicine Research Center and Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaKey Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaTranslational Medicine Research Center and Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaKey Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaTranslational Medicine Research Center and Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaKey Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaTranslational Medicine Research Center and Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaKey Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaTranslational Medicine Research Center and Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaKey Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Pathology, Shanxi Provincial People’s Hospital, The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan, ChinaCancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, ChinaEsophageal squamous cell carcinoma (ESCC) is the most prevalent primary malignant esophageal tumor in China and has a poor prognosis, but lacks effective diagnostic and prognostic biomarkers. Through single-sample gene set enrichment analysis (ssGSEA), we conducted immune genomic analysis based on 28 immune features using transcriptomic data from 155 ESCC cases. We established of two ESCC subtypes characterized by high and low immune profiles, and 352 differentially expressed immune genes were identified between the two subtypes. Performed with univariate and multivariate Cox regression, a novel prognostic prediction model was developed based on three immune-related genes (MAP3K8, SECTM1, IGLV7-43), which has been identified as a relatively accurate, independent, and specific prognostic risk model for ESCC patients in different ESCC cohorts. Furthermore, SECTM1 was upregulated in ESCC tissues and associated with adverse clinical outcomes. In cell experiments, overexpression of SECTM1 effectively promoted the proliferation, migration, and invasion of ESCC cells, while SECTM1 knockdown significantly inhibited these cellular processes. Furthermore, its overexpression promoted macrophage polarization towards the M2-like phenotype and promoted the migration of M2-like macrophage cells and C-C Motif Chemokine Ligand 5 (CCL5) was the key mediator in the pro-cancer effect of SECTM1. In a Conclusion, our study established a prognostic prediction model based on immune-related gene signature, which provided a reliable prognostic tool for ESCC and identified SECTM1 as a potential biomarker in ESCC.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1507227/fullESCCSECTM1immunebiomarkermacrophageCCL5 |
spellingShingle | Pengzhou Kong Pengzhou Kong Pengzhou Kong Ye Jiao Ye Jiao Meng Sun Meng Sun Zhinan Zhou Zhinan Zhou Yingying Zhang Yingying Zhang Xin Yang Xin Yang Jing Ren Jing Ren Mengyuan Yang Mengyuan Yang Yanyan Dong Yanyan Dong Yanyan Dong Bin Song SECTM1 acts as an immune-related biomarker of poor prognosis and promotes cancer progression by modulating M2 macrophage polarization in esophageal squamous cell carcinoma Frontiers in Immunology ESCC SECTM1 immune biomarker macrophage CCL5 |
title | SECTM1 acts as an immune-related biomarker of poor prognosis and promotes cancer progression by modulating M2 macrophage polarization in esophageal squamous cell carcinoma |
title_full | SECTM1 acts as an immune-related biomarker of poor prognosis and promotes cancer progression by modulating M2 macrophage polarization in esophageal squamous cell carcinoma |
title_fullStr | SECTM1 acts as an immune-related biomarker of poor prognosis and promotes cancer progression by modulating M2 macrophage polarization in esophageal squamous cell carcinoma |
title_full_unstemmed | SECTM1 acts as an immune-related biomarker of poor prognosis and promotes cancer progression by modulating M2 macrophage polarization in esophageal squamous cell carcinoma |
title_short | SECTM1 acts as an immune-related biomarker of poor prognosis and promotes cancer progression by modulating M2 macrophage polarization in esophageal squamous cell carcinoma |
title_sort | sectm1 acts as an immune related biomarker of poor prognosis and promotes cancer progression by modulating m2 macrophage polarization in esophageal squamous cell carcinoma |
topic | ESCC SECTM1 immune biomarker macrophage CCL5 |
url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1507227/full |
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