Research advances in metabolic profiling and imaging markers of invasive front of OSCC

doi:10.12439/kqhm.1005-4979.2025.05.001

《Journal of Oral and Maxillofacial Surgery》 ›› 2025, Vol. 35 ›› Issue (5): 331-342. doi: 10.12439/kqhm.1005-4979.2025.05.001

• Critical Review • Next Articles

Research advances in metabolic profiling and imaging markers of invasive front of OSCC

LIU Yu(), KONG Jianlu, ZHU Ziyu, ZHANG Chuhan, YANG Yemu, ZHOU Siyi, HONG Kaizhe, YU Mengfei, WANG Huiming()

Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310020, China

Received:2025-06-03 Accepted:2025-09-18 Published:2025-10-28 Online:2025-10-28

口腔鳞状细胞癌侵袭前缘的代谢特征及其影像标志物的研究进展

刘宇(), 孔建鲁, 朱子羽, 章楚晗, 杨也牧, 周思怡, 洪凯哲, 俞梦飞, 王慧明()

浙江大学医学院附属口腔医院，浙江大学口腔医学院，浙江省口腔疾病临床医学研究中心，浙江省口腔生物医学研究重点实验室，浙江大学癌症研究院，口腔生物材料与器械浙江省工程研究中心，杭州 310020

通讯作者: 王慧明，教授. E-mail: whmwhm@zju.edu.cn

作者简介:

刘宇，现任浙江大学医学院附属口腔医院副主任医师、博士生导师，担任口腔颌面外科临床负责人、学科副主任及教研室副主任，浙江省“万人计划”医疗卫生青年创新人才，浙江省首批“小而强”创新团队临床负责人。现任中国抗癌协会口腔颌面肿瘤整合康复委员会常务委员、中国非公立医疗机构协会口腔颌面外科专业委员会常务委员、全国卫生产业企业管理协会肿瘤分会常务委员、中华口腔医学会头颈肿瘤专业委员会委员、中华口腔医学会口腔急诊专业委员会委员、中国抗癌协会口腔颌面肿瘤整合青年委员会常务委员、中国中西医结合学会口腔医学专委会委员、浙江省康复医学会修复重建专业委员会常务委员、浙江省医师协会青年医师分会委员、浙江省抗癌协会口腔颌面肿瘤专业委员会委员等。刘宇副主任医师长期致力于口腔颌面外科、口腔颌面头颈肿瘤精准诊治与功能性重建、微创数字化外科等临床与科研工作，主持多项研究课题，并发表多篇高质量科研论文。临床工作中，他带领团队于院内首次成功开展多项高难度恶性肿瘤根治和功能重建等手术，在浙江省内率先开展口腔颌面肿瘤全内镜手术；主持开展多项新技术、新项目，并参与发表相关专家共识。曾获“全国优秀指导教师”“浙大口腔好医师”称号，指导的学生获2024全国口腔医学临床技能大赛一等奖。刘宇，副主任医师. E-mail: 7514061@zju.edu.cn

王慧明，教授，博士生导师，浙江大学口腔医学研究所所长、浙江大学医学院附属口腔医院主任医师、浙江省口腔生物医学重点实验室主任、浙江大学特聘教授、国务院政府特殊津贴专家。王慧明教授致力于口腔种植与口腔颌面外科的临床与基础研究工作30余年，近5年来，在Biomaterials、Journal of Dental Research、ACS Applied Materials Interfaces、Stem Cell等期刊发表SCI论文140余篇。其研究主要涵盖以下方面：种植体表面改性、生物学评价与新型种植体研发；血管化预成型组织工程肌肉骨骼瓣修复下颌复合缺损；下颌组织缺损功能重建的创新技术及相关基础研究。主持多项国家自然科学基金及省部级重大科研项目，曾获得省部级科技进步奖8项，包括“下颌组织缺损功能重建的创新技术”及相关创新技术与基础研究等。他还主持制定了《无牙颌数字化种植修复技术专家共识》等3项行业共识，积极推动口腔及颌面重建诊疗流程的规范化和标准化。

基金资助:
浙江省“尖兵领雁+X”科技计划(2025C02101)

Abstract

Abstract:

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck, accounting for 90% of all oral cancers. The disease is prone to recurrence, invasion, and metastasis, leading to a poor prognosis with a five-year survival rate of approximately 50%–60%. The invasive front of OSCC is a critical region for tumor recurrence and metastasis, characterized by high heterogeneity and aggressiveness. Metabolic reprogramming in this area drives malignant progression and offers potential targets for the development of imaging biomarkers. This review summarizes the metabolic features of the invasive front and their underlying molecular mechanisms, with a focus on how aberrant activation of pathways such as glucose metabolism, lipid metabolism, and amino acid metabolism promotes tumor cell migration, invasion, and immune evasion. Additionally, it discusses the translational applications of metabolic traits at the OSCC invasive front as imaging biomarkers, including the application value of spatial metabolomics, Raman spectroscopy, and positron emission tomography/computed tomography (PET-CT) in predicting tumor boundaries and visualizing metabolic profiles of the invasive front. In the future, integrating multi-omics data with imaging analysis may facilitate the development of clinical translation pathways based on metabolic markers of the invasive front, thereby providing new strategies for precise diagnosis, surgical navigation, and prognosis evaluation of OSCC, and advancing precision diagnosis and treatment for OSCC at the level of small-molecule metabolites.

Key words: oral squamous cell carcinoma, invasive front, metabolic reprogramming, spatial metabolomics, Raman spectroscopy, positron emission tomography/computed tomography

摘要：

口腔鳞状细胞癌（oral squamous cell carcinoma，OSCC）是头颈部最常见的恶性肿瘤，占所有口腔癌的90%。该病易复发和发生侵袭转移，患者预后较差，5年生存率约50%~60%。OSCC的侵袭前缘是肿瘤复发和转移的关键区域，具有高度异质性和侵袭性。该区域的代谢重编程驱动肿瘤恶性进展，并为影像学生物标志物的开发提供了潜在靶点。本文综述了侵袭前缘的代谢特征及其分子机制，重点探讨了糖代谢、脂质代谢和氨基酸代谢等通路的异常活化如何促进肿瘤细胞的迁移、侵袭及免疫逃逸；同时，分析了OSCC侵袭前缘代谢特征作为影像标志物的转化应用，包括空间代谢组学技术、拉曼光谱及正电子发射断层显像-计算机断层扫描（positron emission tomography / computed tomography，PET-CT）等在预测肿瘤边界、可视化侵袭前缘代谢特征中的应用价值。未来，通过整合多组学数据与影像学分析，有望构建基于侵袭前缘代谢标志物的临床转化路径，从而为OSCC的精准诊断、手术导航及预后评估提供新策略，推动该疾病在小分子代谢物层面的精准诊疗进展。

关键词: 口腔鳞状细胞癌, 侵袭前缘, 代谢重编程, 空间代谢组, 拉曼光谱, 正电子发射断层显像-计算机断层扫描

LIU Yu, KONG Jianlu, ZHU Ziyu, ZHANG Chuhan, YANG Yemu, ZHOU Siyi, HONG Kaizhe, YU Mengfei, WANG Huiming. Research advances in metabolic profiling and imaging markers of invasive front of OSCC[J]. 《Journal of Oral and Maxillofacial Surgery》, 2025, 35(5): 331-342.

刘宇, 孔建鲁, 朱子羽, 章楚晗, 杨也牧, 周思怡, 洪凯哲, 俞梦飞, 王慧明. 口腔鳞状细胞癌侵袭前缘的代谢特征及其影像标志物的研究进展[J]. 《口腔颌面外科杂志》, 2025, 35(5): 331-342.

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URL: https://journal06.magtech.org.cn/Jweb_joms/EN/10.12439/kqhm.1005-4979.2025.05.001

https://journal06.magtech.org.cn/Jweb_joms/EN/Y2025/V35/I5/331

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技术参数	PET-CT	空间代谢组学	拉曼光谱
原理	基于放射性示踪剂（如¹⁸F-FDG）的代谢成像	原位质谱分析分子空间分布	分子振动光谱(非弹性光散射)
分辨率	4~5 mm	10~200 μm	0.5~1.0 μm
检测深度	全身扫描	组织切片表面（0~10 μm），需切片	表面下50~100 μm（共聚焦拉曼）
代谢信息	糖代谢（Warburg效应）为主	多分子覆盖（脂质、氨基酸、糖等）；分子量<1 500 Da	全分子指纹（蛋白质、脂质、核酸等）；分子量无限制（依赖振动峰）
侵入性	低（静脉注射）	离体组织检测	无（可活体检测）
临床应用成熟度	高（常规肿瘤分期）	科研阶段（少数临床试验）	探索阶段
优势	全身性评估、定量标准化[基于标准摄取值（standardized uptake value，SUV）]	多代谢物同步检测、空间关联分析	无标记、高分辨率、可行活体动态监测
局限性	分辨率低、辐射暴露、成本高	设备昂贵、样本制备复杂	信号弱、深度受限、数据库不完善
典型OSCC应用	评估肿瘤浸润深度及转移情况，并可基于最大标准摄取值（SUVmax）预测预后	切缘鉴定（天冬氨酸、鞘脂、胆固醇硫酸盐、油酸等）	术中边界界定（色氨酸、角蛋白、水含量、脂质含量等）

技术参数	PET-CT	空间代谢组学	拉曼光谱
原理	基于放射性示踪剂（如¹⁸F-FDG）的代谢成像	原位质谱分析分子空间分布	分子振动光谱(非弹性光散射)
分辨率	4~5 mm	10~200 μm	0.5~1.0 μm
检测深度	全身扫描	组织切片表面（0~10 μm），需切片	表面下50~100 μm（共聚焦拉曼）
代谢信息	糖代谢（Warburg效应）为主	多分子覆盖（脂质、氨基酸、糖等）；分子量<1 500 Da	全分子指纹（蛋白质、脂质、核酸等）；分子量无限制（依赖振动峰）
侵入性	低（静脉注射）	离体组织检测	无（可活体检测）
临床应用成熟度	高（常规肿瘤分期）	科研阶段（少数临床试验）	探索阶段
优势	全身性评估、定量标准化[基于标准摄取值（standardized uptake value，SUV）]	多代谢物同步检测、空间关联分析	无标记、高分辨率、可行活体动态监测
局限性	分辨率低、辐射暴露、成本高	设备昂贵、样本制备复杂	信号弱、深度受限、数据库不完善
典型OSCC应用	评估肿瘤浸润深度及转移情况，并可基于最大标准摄取值（SUVmax）预测预后	切缘鉴定（天冬氨酸、鞘脂、胆固醇硫酸盐、油酸等）	术中边界界定（色氨酸、角蛋白、水含量、脂质含量等）

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