Investigating lung cancer microenvironment from cell segmentation of pathological image and its application in prognostic stratification

Abstract Lung cancer, particularly adenocarcinoma, ranks high in morbidity and mortality rates worldwide, with a relatively low five-year survival rate. To achieve precise prognostic assessment and clinical intervention for patients, thereby enhancing their survival prospects, there is an urgent nee...

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Main Authors: Xu Zhang, Zi-Han Zhang, Yong-Min Liu, Shi-Lei Zhao, Xu-Tong Zhao, Li-Zhi Zhang, Chun-Dong Gu, Yi Zhao
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-85532-y
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author Xu Zhang
Zi-Han Zhang
Yong-Min Liu
Shi-Lei Zhao
Xu-Tong Zhao
Li-Zhi Zhang
Chun-Dong Gu
Yi Zhao
author_facet Xu Zhang
Zi-Han Zhang
Yong-Min Liu
Shi-Lei Zhao
Xu-Tong Zhao
Li-Zhi Zhang
Chun-Dong Gu
Yi Zhao
author_sort Xu Zhang
collection DOAJ
description Abstract Lung cancer, particularly adenocarcinoma, ranks high in morbidity and mortality rates worldwide, with a relatively low five-year survival rate. To achieve precise prognostic assessment and clinical intervention for patients, thereby enhancing their survival prospects, there is an urgent need for more accurate stratification schemes. Currently, the TNM staging system is predominantly used in clinical practice for prognostic evaluation, but its accuracy is constrained by the reliance on physician experience. Although biomarker discovery based on molecular pathology offers a new perspective for prognostic assessment, its dependence on expensive gene panel testing limits its widespread clinical application. Pathological images contain abundant diagnostic information, providing a new avenue for prognostic evaluation. In this study, we employed advanced Hover-Net technology to accurately quantify the abundance of epithelial cells, lymphocytes, macrophages, and neutrophils from pathological images, and delved into the clinical and biological significance of these cellular abundances. Our research findings reveal that, in contrast to patients classified as N0 stage, those belonging to the N1 stage demonstrated a marked elevation in the infiltration of epithelial cells, lymphocytes, macrophages, and neutrophils. Notably, the infiltration patterns of lymphocytes and neutrophils exhibited an inverse relationship with the activation status of numerous pivotal gene pathways, including the HALLMARK_HEME_METABOLISM pathway. Furthermore, our analysis distinguished FABP7 as a prognostic biomarker, exhibiting pronounced differential expression between patients with high and low levels of neutrophil infiltration, indicate that cellular abundance analysis based on pathological images can provide a more accurate and cost-effective prognostic evaluation, offering new strategies for the clinical management of lung adenocarcinoma.
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spelling doaj-art-c4922f383b84496eb922ee9b0ea4c8f32025-01-12T12:19:17ZengNature PortfolioScientific Reports2045-23222025-01-0115111210.1038/s41598-025-85532-yInvestigating lung cancer microenvironment from cell segmentation of pathological image and its application in prognostic stratificationXu Zhang0Zi-Han Zhang1Yong-Min Liu2Shi-Lei Zhao3Xu-Tong Zhao4Li-Zhi Zhang5Chun-Dong Gu6Yi Zhao7Department of Thoracic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian Medical UniversityDepartment of Intelligent Medical Engineering, Medical School of Tianjin University, Tianjin UniversityDepartment of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian Medical UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian Medical UniversityDepartment of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian Medical UniversityDepartment of Pathology, The First Affiliated Hospital of Dalian Medical University, Dalian Medical UniversityDepartment of Thoracic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian Medical UniversityDepartment of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian Medical UniversityAbstract Lung cancer, particularly adenocarcinoma, ranks high in morbidity and mortality rates worldwide, with a relatively low five-year survival rate. To achieve precise prognostic assessment and clinical intervention for patients, thereby enhancing their survival prospects, there is an urgent need for more accurate stratification schemes. Currently, the TNM staging system is predominantly used in clinical practice for prognostic evaluation, but its accuracy is constrained by the reliance on physician experience. Although biomarker discovery based on molecular pathology offers a new perspective for prognostic assessment, its dependence on expensive gene panel testing limits its widespread clinical application. Pathological images contain abundant diagnostic information, providing a new avenue for prognostic evaluation. In this study, we employed advanced Hover-Net technology to accurately quantify the abundance of epithelial cells, lymphocytes, macrophages, and neutrophils from pathological images, and delved into the clinical and biological significance of these cellular abundances. Our research findings reveal that, in contrast to patients classified as N0 stage, those belonging to the N1 stage demonstrated a marked elevation in the infiltration of epithelial cells, lymphocytes, macrophages, and neutrophils. Notably, the infiltration patterns of lymphocytes and neutrophils exhibited an inverse relationship with the activation status of numerous pivotal gene pathways, including the HALLMARK_HEME_METABOLISM pathway. Furthermore, our analysis distinguished FABP7 as a prognostic biomarker, exhibiting pronounced differential expression between patients with high and low levels of neutrophil infiltration, indicate that cellular abundance analysis based on pathological images can provide a more accurate and cost-effective prognostic evaluation, offering new strategies for the clinical management of lung adenocarcinoma.https://doi.org/10.1038/s41598-025-85532-yLung adenocarcinoma (LUAD)Prognostic biomarkersHover-net cell segmentation technologyMultidimensional biological analysis
spellingShingle Xu Zhang
Zi-Han Zhang
Yong-Min Liu
Shi-Lei Zhao
Xu-Tong Zhao
Li-Zhi Zhang
Chun-Dong Gu
Yi Zhao
Investigating lung cancer microenvironment from cell segmentation of pathological image and its application in prognostic stratification
Scientific Reports
Lung adenocarcinoma (LUAD)
Prognostic biomarkers
Hover-net cell segmentation technology
Multidimensional biological analysis
title Investigating lung cancer microenvironment from cell segmentation of pathological image and its application in prognostic stratification
title_full Investigating lung cancer microenvironment from cell segmentation of pathological image and its application in prognostic stratification
title_fullStr Investigating lung cancer microenvironment from cell segmentation of pathological image and its application in prognostic stratification
title_full_unstemmed Investigating lung cancer microenvironment from cell segmentation of pathological image and its application in prognostic stratification
title_short Investigating lung cancer microenvironment from cell segmentation of pathological image and its application in prognostic stratification
title_sort investigating lung cancer microenvironment from cell segmentation of pathological image and its application in prognostic stratification
topic Lung adenocarcinoma (LUAD)
Prognostic biomarkers
Hover-net cell segmentation technology
Multidimensional biological analysis
url https://doi.org/10.1038/s41598-025-85532-y
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