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从病理图像的细胞分割研究肺癌微环境及其在预后分层中的应用。

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

作者信息

Zhang Xu, Zhang Zi-Han, Liu Yong-Min, Zhao Shi-Lei, Zhao Xu-Tong, Zhang Li-Zhi, Gu Chun-Dong, Zhao Yi

机构信息

Department of Thoracic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian Medical University, Dalian, 116011, China.

Clinical Skills Center of Academic Affairs Office of Dalian Medical University, Dalian Medical University, Dalian, 116044, China.

出版信息

Sci Rep. 2025 Jan 11;15(1):1704. doi: 10.1038/s41598-025-85532-y.

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.

摘要

肺癌,尤其是腺癌,在全球发病率和死亡率中位居高位,五年生存率相对较低。为了对患者进行精确的预后评估和临床干预,从而提高他们的生存前景,迫切需要更准确的分层方案。目前,TNM分期系统主要用于临床实践中的预后评估,但其准确性受到对医生经验依赖的限制。尽管基于分子病理学的生物标志物发现为预后评估提供了新视角,但其对昂贵基因检测板检测的依赖限制了其在临床中的广泛应用。病理图像包含丰富的诊断信息,为预后评估提供了新途径。在本研究中,我们采用先进的Hover-Net技术从病理图像中准确量化上皮细胞、淋巴细胞、巨噬细胞和中性粒细胞的丰度,并深入探讨这些细胞丰度的临床和生物学意义。我们的研究结果表明,与N0期患者相比,N1期患者的上皮细胞、淋巴细胞、巨噬细胞和中性粒细胞浸润显著增加。值得注意的是,淋巴细胞和中性粒细胞的浸润模式与包括HALLMARK_HEME_METABOLISM途径在内的众多关键基因途径的激活状态呈负相关。此外,我们的分析将FABP7鉴定为一种预后生物标志物,在中性粒细胞浸润水平高和低的患者之间表现出明显的差异表达,这表明基于病理图像的细胞丰度分析可以提供更准确且经济高效的预后评估,为肺腺癌的临床管理提供新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd5e/11724888/d2f2aa74cd0b/41598_2025_85532_Fig1_HTML.jpg

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