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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Main Authors: Pengzhou Kong, Ye Jiao, Meng Sun, Zhinan Zhou, Yingying Zhang, Xin Yang, Jing Ren, Mengyuan Yang, Yanyan Dong, Bin Song
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Immunology
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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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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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