FFPE Validation of a Survival Gene Signature in HPV-Negative Oral Cavity Cancer

HPV 阴性口腔癌生存基因特征的 FFPE 验证

基本信息

批准号：
9197967
负责人：
CHU CHEN
金额：
$ 61.2万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-01-01 至 2020-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9197967
关键词：
Adjuvant American Joint Committee on Cancer Biological Assay Breast Canada Cancer Center Cancer Patient Cessation of life Characteristics Clinical Colon DNA Data Set Diagnostic Disease Formalin France Fred Hutchinson Cancer Research Center Freezing Gene Chips Gene Expression Gene Expression Profile Gene Expression Profiling Genes Goals Head and Neck Cancer Hospitals Human Papillomavirus International Agency for Research on Cancer Lead Lung Malignant Neoplasms Michigan Modality Modeling Molecular Mouth Neoplasms Multi-Institutional Clinical Trial Operative Surgical Procedures Oral Stage Oral cavity Oropharyngeal Pain Paraffin Embedding Participant Patient Care Patients Phase Physicians Prognostic Marker Radiation Radiosurgery Running Sampling Staging Technology Testing Time Training Tumor Tissue Tumor stage Utah Validation Washington Work base chemotherapy clinical Diagnosis clinical care clinical practice cohort cost effective genetic signature global health improved malignant breast neoplasm malignant mouth neoplasm malignant oropharynx neoplasm molecular marker mouth squamous cell carcinoma nano-string novel orofacial outcome forecast personalized management personalized medicine prognostic prospective public health relevance research clinical testing survival outcome survival prediction treatment choice tumor

项目摘要

DESCRIPTION (provided by applicant): Squamous cell carcinoma of the oral cavity and oropharynx (OSCC) is a substantial global health burden, with an estimate of 529,000 new cases and over 292,000 deaths in 2012. OSCC can be further subclassified into entities with a different prognosis. For example, patients with human papillomavirus (HPV)-positive oropharyngeal cancer (OPC) tend to have better survival than those with HPV-negative OPC. However, prognostication for oral cavity cancer, which comprises the majority of OSCC and is mostly HPV-negative, is largely based on clinical staging, and molecular markers that could be used in clinical practice have not been identified. There is an urgent need to develop better prognostic markers for personalized clinical management of these patients. Our long-term goal is to develop simple, reliable, and cost-effective gene expression signatures to guide the management of OSCC patients. In our prior work (the Oralchip study, 5 R01 CA095419, PI: Chu Chen), we have identified a prognostic gene expression signature in tumor tissue that showed a greater ability than tumor stage to predict OSCC-specific survival for patients with HPV-negative OSCC, irrespective of types of treatment. We validated this signature using an independent set of patients with oral cavity cancer from the MD Anderson Cancer Center. This was the first demonstration of a gene expression signature that provides prognostic information beyond AJCC stage for oral cavity cancer patients. The specific aims of the proposed study are to leverage the available diagnostic tumor blocks, demographic and clinical information and survival outcomes of oral cavity cancer patients from five head and neck cancer studies (Fred Hutchinson Cancer Research Center/Univ. of Washington; Univ. of Calgary; Univ. of Michigan; Univ. of Utah; and the International Agency of Research on Cancer) to 1) test the hypothesis that the prognostic ability of our 9-gene signature for HPV-negative OSCC patients, that was developed and validated using snap frozen fresh tumor tissue and Affymetrix gene expression arrays, can be transported to formalin-fixed paraffin embedded (FFPE) hospital tumor blocks of HPV-negative, p16-negative oral cavity cancer patients and NanoString nCounter technology, and to build prediction models for overall and oral cavity cancer-specific survival; 2) validate th prediction models using independent cohorts of HPV-negative, p16-negative oral cavity cancer patients; and 3) evaluate whether the ability of the gene signature to predict survival, overall an OSCC-specific, would be influenced by treatment modalities (surgery alone; surgery + radiation; and surgery + radiation + chemotherapy) that collectively were administered to ~90% of the study participants. This study is significant and novel because it has the potential to deliver, fr the first time, a rapid, inexpensive, and reliable multi-marker assay that can be run on hospital diagnostic FFPE samples, routinely prepared by the hospital at the time of surgery, to improve survival prediction of HPV-negative oral cavity cancer patients, and thus lead to improved clinical care of patients with this often lethal disease.

描述（由申请人提供）：口腔和口腔咽部（OSCC）的鳞状细胞癌是全球巨大的健康负担，估计为529,000例新病例，2012年超过292,000例死亡。OSCC可以进一步将其进一步分为具有不同预后的实体。例如，人乳头瘤病毒（HPV） - 阳性口咽癌（OPC）的患者比患有HPV阴性OPC的患者的存活率往往更好。但是，对大多数OSCC组成的口腔癌的预后主要是HPV阴性，主要基于临床分期，并且尚未在临床实践中使用的分子标记。迫切需要为这些患者的个性化临床管理开发更好的预后标记。我们的长期目标是开发简单，可靠和具有成本效益的基因表达特征，以指导OSCC患者的管理。在我们先前的工作（口腔琴研究，5 R01 CA095419，PI：Chu Chen）中，我们已经在肿瘤组织中鉴定出预后的基因表达特征，这些能力比肿瘤期更大的能力预测HPV阴性OSCC患者的OSCC特异性生存率，而治疗类型的治疗类型不适合治疗类型。我们使用MD安德森癌症中心的一组独立的口腔癌患者验证了该签名。这是基因表达特征的首次演示，该标志为口腔癌患者提供了AJCC阶段以外的预后信息。拟议研究的具体目的是利用来自五个头和颈部癌症研究的口腔癌症患者的可用诊断肿瘤块，人口统计和临床信息以及口腔癌症患者的生存结果（华盛顿州的弗雷德·哈钦森癌研究中心/卡尔加里大学；密歇根大学； 9-gene signature for HPV-negative OSCC patients, that was developed and validated using snap frozen fresh tumor tissue and Affymetrix gene expression arrays, can be transported to formalin-fixed paraffin embedded (FFPE) hospital tumor blocks of HPV-negative, p16-negative oral cavity cancer patients and NanoString nCounter technology, and to build prediction models for overall and oral腔癌特异性生存； 2）使用独立的HPV阴性，P16阴性口腔癌患者验证预测模型； 3）评估基因签名预测生存的能力（总体OSCC特异性）是否会受到治疗方式（单独手术；手术 +辐射 +辐射 +辐射 +辐射 +化学疗法），该方法统称为约90％的研究参与者。这项研究是重要和新颖的，因为它有可能第一次提供，这是一种快速，廉价且可靠的多标志物测定法，可以在医院在手术时由医院常规准备的医院诊断FFPE样品进行，以改善HPV阴性预测的HPV-Negaltic癌症患者的生存预测，从而改善了临床疾病的临床护理患者。