MicroRNA marker-based prognosis of oral cancer survival

基于 MicroRNA 标记的口腔癌生存预后

• 批准号: 8581898
• 负责人: Angela Jiyeon Yoon
• 金额: $ 12万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8581898
• 关键词: Accounting; Adjuvant; Age; American; Area; Basic Science; Bioinformatics; Cancer Patient; Cessation of life; Clinical; Clinical Management; Cost Control; Data; Decision Making; Dental; Diagnosis; Diagnostic Neoplasm Staging; Disease; Disease-Free Survival; Enrollment; Evaluation; Excision; Future; Gender; Gene Expression; Gene Targeting; Generations; Genome; Goals; Grant; Hour; Investigator-Initiated Research; Malignant Neoplasms; Mediating; Medical center; Methods; MicroRNAs; Modality; Molecular; Molecular Profiling; National Institute of Dental and Craniofacial Research; Newly Diagnosed; Oncogenic; Operative Surgical Procedures; Outcome; Pathway interactions; Patients; Phase; Procedures; Process; Prognostic Marker; Prospective Studies; Radiation therapy; Research; Research Personnel; Research Project Grants; Scientist; Selection for Treatments; Sensitivity and Specificity; Staging; Subgroup; Survival Rate; Therapeutic Agents; Time; Tissue Sample; Translating; Tumor Tissue; Tumor stage; United States; Validation; Work; anticancer research; base; candidate marker; chemotherapeutic agent; chemotherapy; cohort; deep sequencing; experience; follow-up; genome wide association study; genome-wide; improved; innovation; insight; malignant mouth neoplasm; mouth squamous cell carcinoma; next generation sequencing; novel marker; oral carcinogenesis; outcome forecast; patient oriented research; prognostic; programs; public health relevance; research clinical testing; skills; treatment response; tumor

DESCRIPTION (provided by applicant): Each year an estimated 400,000 people globally, among them 30,000 Americans, are newly diagnosed with oral squamous cell carcinoma (OSCC). The 5-year survival rate is only about 50%, accounting for 1 death every hour in the US. Following the surgical removal of tumor, selection of adjuvant treatment is made largely based on the clinical stage of the tumor. However, despite the advances in treatment, survival rate has not improved significantly over the last several decades. Discovery of a strategy to identify cancer patients with poor prognosis and selectively directing those patients for additional adjuvant chemo/radiation therapy will significantly improve the cancer survival rate. Hence, it is imperative to discover a reliable and accurate prognostic indicator of oral cancer survival to be applied in the treatment decision making process and improve the overall survival of patients with oral cancer. The aim of the proposed study is to develop and validate a microRNA (miR) marker-based prognostic modality for oral cancer survival (5-year disease free survival versus death within 5-years). Those with less favorable prognosis with surgery alone may then be directed for additional treatment. In the initial phase of the study, we propose to perform a genome-wide miR expression assessment via next generation sequencing in 10 OSCC tissue samples from patients who had 5-year disease-free survival (Group 1), compared with 10 of those from age- and gender-matched cancer patients who died of the disease within 5 years (Group 2). Bioinformatics analysis will be performed to integrate sequencing data to identify miR target genes and miR-mediated oncogenic network and pathways. Top miR candidates that can identify those patients with poor prognosis with high sensitivity and specificity will be selected to form a prognostic miR marker panel in Aim 1. The candidate marker panel will then be validated in Aim 2 in additional 40 Group 1-Group 2 pairs using RT-qPCR. The proposed innovative approach has never been applied for prognosis of oral cancer survival before; it offers scalability and cost containment while allowing an agnostic approach to discovery of molecular changes across the genome that is followed by independent validation. Developing a new generation of dental scientists able to translate basic science into actionable clinical information and methods is imperative to progress. This NIDCR Small Grant Program for New Investigators (R03) proposal describes a 2-year research program aimed at developing highly specialized expertise in the molecular management of OSCC. The proposed study will serve as the candidate's platform to develop and fine-tune practical experience and skills in patient-oriented research, to establish independence in the area of oral cancer research, obtain preliminary data that may be used in the near future to support R01 applications and to expand the field of oral carcinogenesis towards a better understanding of this deadly disease. Through this R03 program for the new investigators, the candidate will reach her long-term goal of becoming an independent investigator with expertise in the management of oral cancer.

描述（由申请人提供）：全球每年估计有40万人，其中3万人是美国人，被新诊断为口腔鳞状细胞癌（OSCC）。5年生存率仅为50%左右，在美国每小时就有1例死亡。手术切除肿瘤后，辅助治疗的选择主要基于肿瘤的临床阶段。然而，尽管治疗取得了进展，但在过去几十年中，生存率并没有显著提高。发现一种识别预后不良的癌症患者并选择性地指导这些患者进行额外的辅助化疗/放疗的策略将显著提高癌症存活率。因此，迫切需要找到可靠、准确的口腔癌生存预后指标，应用于治疗决策过程，提高口腔癌患者的总生存率。这项研究的目的是开发和验证一种基于microRNA（miR）标记的口腔癌生存预后模式（5年无病生存与5年内死亡）。那些预后不太好的单独手术，然后可以直接进行额外的治疗。在研究的初始阶段，我们建议通过下一代测序对来自5年无病生存患者（第1组）的10个OSCC组织样本进行全基因组miR表达评估，与之相比，年龄和性别匹配的癌症患者中的10个在5年内死于该疾病（第2组）。将进行生物信息学分析以整合测序数据，以鉴定miR靶基因和miR介导的致癌网络和途径。将选择能够以高灵敏度和特异性鉴定具有不良预后的那些患者的最佳miR候选物以形成目标1中的预后miR标志物组。然后在目标2中使用RT-qPCR在另外40个组1-组2对中验证候选标记物组。所提出的创新方法以前从未应用于口腔癌生存的预后;它提供了可扩展性和成本控制，同时允许一种不可知的方法来发现整个基因组的分子变化，然后进行独立验证。培养能够将基础科学转化为可操作的临床信息和方法的新一代牙科科学家是进步的必要条件。NIDCR的新研究者小额资助计划（R03）提案描述了一项为期2年的研究计划，旨在发展口腔鳞状细胞癌分子管理方面的高度专业化的专业知识。拟议的研究将作为候选人的平台，以发展和微调以患者为导向的研究的实践经验和技能，建立在口腔癌研究领域的独立性，获得可能在不久的将来用于支持R01应用的初步数据，并扩大口腔癌发生领域，以更好地了解这种致命的疾病。通过新研究者的R03计划，候选人将实现成为一名具有口腔癌管理专业知识的独立研究者的长期目标。