Integrating artificial intelligence-driven digital pathology and genomics to establish patient-derived organoids as new approach methodologies for drug response in head and neck cancer

IF 4 2区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Oral oncology Pub Date : 2025-12-01 Epub Date: 2025-11-09 DOI:10.1016/j.oraloncology.2025.107742

Rose Doerfler , Jie Chen , Carl Kim , Joshua D. Smith , Micah Harris , Krishna B. Singh , Brian Isett , Rebekah E. Dadey , Daniel D. Brown , Adrian V. Lee , Xuefeng Wang , Matthew E. Spector , Seungwon Kim , Shaum Sridharan , Kevin Contrera , Katelyn Smith , Carly Reeder , Maureen Lyons , Jianhua Luo , Silvia Liu , Riyue Bao

{"title":"Integrating artificial intelligence-driven digital pathology and genomics to establish patient-derived organoids as new approach methodologies for drug response in head and neck cancer","authors":"Rose Doerfler , Jie Chen , Carl Kim , Joshua D. Smith , Micah Harris , Krishna B. Singh , Brian Isett , Rebekah E. Dadey , Daniel D. Brown , Adrian V. Lee , Xuefeng Wang , Matthew E. Spector , Seungwon Kim , Shaum Sridharan , Kevin Contrera , Katelyn Smith , Carly Reeder , Maureen Lyons , Jianhua Luo , Silvia Liu , Riyue Bao","doi":"10.1016/j.oraloncology.2025.107742","DOIUrl":null,"url":null,"abstract":"<div><div>Patient-derived organoids (PDOs) emerge as advanced 3D ex vivo New Approach Methodologies (NAM) preclinical models, offering significant advantages over traditional cell lines and monolayer cultures for therapeutic development. In this study, we established PDOs from surgically resected fresh tissues of human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) across anatomical sites, tumor T-categories, and sample types. These PDOs faithfully recapitulate the tumor’s pathology, mutational profile, and drug response. To enable rapid classification of PDO identity, we developed a new convolutional neural network (CNN) model, TransferNet-PDO, which accurately distinguished tumor <em>versus</em> normal PDOs in culture using digital histopathology images (AUC ≥ 0.88). PDOs maintained stable cultures and were cryopreserved between passages 5 and 12. Immunohistochemistry (IHC) staining (PanCK, p63, Cytokeratin 13, Ki67) confirmed squamous phenotype and histologic aggression of the original tumor. For tumors harboring TP53 mutations by whole-exome sequencing (WES), PDOs retained the corresponding p53 functional status as confirmed by IHC (enhanced or loss of protein expression). Somatic mutational landscape revealed that PDOs preserved driver somatic mutations, copy number variations (CNVs), and clonal architecture including low-prevalence subclones. Drug sensitivity assessment of PDOs showed that cisplatin reduced cell viability, whereas cetuximab and lenvatinib had minimal effects. Chemoradiation led to greater tumor organoid killing compared to radiation or chemotherapy alone. This study presents an integrated HNSCC PDO platform combining tissue biobanking, organoid establishment, multiomics characterization, functional drug screening, and AI-driven histopathologic classification, providing a comprehensive and scalable system for translational cancer research.</div></div>","PeriodicalId":19716,"journal":{"name":"Oral oncology","volume":"171 ","pages":"Article 107742"},"PeriodicalIF":4.0000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oral oncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1368837525005718","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/11/9 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}

引用次数: 0

Abstract

Patient-derived organoids (PDOs) emerge as advanced 3D ex vivo New Approach Methodologies (NAM) preclinical models, offering significant advantages over traditional cell lines and monolayer cultures for therapeutic development. In this study, we established PDOs from surgically resected fresh tissues of human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) across anatomical sites, tumor T-categories, and sample types. These PDOs faithfully recapitulate the tumor’s pathology, mutational profile, and drug response. To enable rapid classification of PDO identity, we developed a new convolutional neural network (CNN) model, TransferNet-PDO, which accurately distinguished tumor versus normal PDOs in culture using digital histopathology images (AUC ≥ 0.88). PDOs maintained stable cultures and were cryopreserved between passages 5 and 12. Immunohistochemistry (IHC) staining (PanCK, p63, Cytokeratin 13, Ki67) confirmed squamous phenotype and histologic aggression of the original tumor. For tumors harboring TP53 mutations by whole-exome sequencing (WES), PDOs retained the corresponding p53 functional status as confirmed by IHC (enhanced or loss of protein expression). Somatic mutational landscape revealed that PDOs preserved driver somatic mutations, copy number variations (CNVs), and clonal architecture including low-prevalence subclones. Drug sensitivity assessment of PDOs showed that cisplatin reduced cell viability, whereas cetuximab and lenvatinib had minimal effects. Chemoradiation led to greater tumor organoid killing compared to radiation or chemotherapy alone. This study presents an integrated HNSCC PDO platform combining tissue biobanking, organoid establishment, multiomics characterization, functional drug screening, and AI-driven histopathologic classification, providing a comprehensive and scalable system for translational cancer research.

查看原文本刊更多论文

整合人工智能驱动的数字病理学和基因组学，建立患者来源的类器官，作为头颈癌药物反应的新方法方法。

患者源性类器官（PDOs）作为先进的3D离体新方法（NAM）临床前模型出现，与传统细胞系和单层培养物相比，在治疗开发方面具有显著优势。在这项研究中，我们从手术切除的人乳头瘤病毒（HPV）阴性头颈部鳞状细胞癌（HNSCC）的新鲜组织中建立了跨解剖部位、肿瘤t分类和样本类型的PDOs。这些PDOs忠实地概括了肿瘤的病理、突变特征和药物反应。为了实现PDO身份的快速分类，我们开发了一种新的卷积神经网络（CNN）模型TransferNet-PDO，该模型使用数字组织病理学图像（AUC≥0.88）准确区分培养中的肿瘤与正常PDO。pdo保持稳定的培养，并在传代5和12之间冷冻保存。免疫组化（IHC）染色（PanCK, p63, Cytokeratin 13, Ki67）证实原肿瘤呈鳞状表型和组织学侵袭性。对于携带TP53突变的肿瘤，通过全外显子组测序（WES）， PDOs保留了相应的p53功能状态，IHC证实了这一点（蛋白质表达增强或丧失）。体细胞突变景观揭示了PDOs保留了驱动体细胞突变、拷贝数变异（CNVs）和包括低流行亚克隆在内的克隆结构。PDOs的药物敏感性评估显示，顺铂降低了细胞活力，而西妥昔单抗和lenvatinib的影响最小。与单独放疗或化疗相比，放化疗导致更大的肿瘤类器官杀伤。本研究提出了一个集组织生物库、类器官建立、多组学表征、功能药物筛选和人工智能驱动的组织病理学分类为一体的HNSCC PDO集成平台，为转化性癌症研究提供了一个全面、可扩展的系统。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Oral oncology 医学-牙科与口腔外科

CiteScore

8.70

自引率

10.40%

发文量

505

审稿时长

20 days

期刊介绍： Oral Oncology is an international interdisciplinary journal which publishes high quality original research, clinical trials and review articles, editorials, and commentaries relating to the etiopathogenesis, epidemiology, prevention, clinical features, diagnosis, treatment and management of patients with neoplasms in the head and neck. Oral Oncology is of interest to head and neck surgeons, radiation and medical oncologists, maxillo-facial surgeons, oto-rhino-laryngologists, plastic surgeons, pathologists, scientists, oral medical specialists, special care dentists, dental care professionals, general dental practitioners, public health physicians, palliative care physicians, nurses, radiologists, radiographers, dieticians, occupational therapists, speech and language therapists, nutritionists, clinical and health psychologists and counselors, professionals in end of life care, as well as others interested in these fields.