Genomic Predictors of Oral Premalignancy Progression

口腔癌前病变进展的基因组预测因素

• 批准号: 7840924
• 负责人: XIAOFENG ZHOU
• 金额: $ 0.93万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-02 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7840924
• 关键词: Allelic Imbalance; Allelotyping; Award; Bioethics; Bioinformatics; Biological Testing; Biometry; Biopsy; Candidate Disease Gene; Chromosomes, Human, Pair 9; Classification; Clinical; Commit; Development; Development Plans; Disease; Environment; Epithelial; Faculty; Functional disorder; Future; Genes; Genome; Genomics; Goals; Grant; Head and Neck Cancer; Lead; Lesion; Loss of Heterozygosity; Malignant - descriptor; Malignant Neoplasms; Mentors; Molecular; Oral; Oral Pathology; Outcome; Pathway interactions; Patients; Pattern; Phase; Phase Transition; Predictive Value; Prema; Process; Research; Research Personnel; Research Training; Risk; Scientist; Series; Staging; Testing; Tissue Banking; Tissue Banks; Training; Writing; anticancer research; base; candidate validation; career; career development; genome-wide; improved; in vivo; innovation; laser capture microdissection; novel therapeutics; oral premalignancy; programs; responsible research conduct; tool; tumor progression

DESCRIPTION (provided by applicant): This K22 application is to support the scholarly training and career development of Dr. Xiaofeng Charles Zhou to become an independent investigator in head and neck cancer research. This application details the strengths and uniqueness of this proposal pertaining to the candidate, the mentor, the career development plan, the environment and the research plan. The proposed research is to test the hypothesis that there are genomic determinants that distinguish progressing from non-progressing oral precancers. The overall risk of malignant transformation of all grades of oral precancers is approximately 18%. It is impossible to predict progressiveness of any one lesion based on conventional clinical and histological features. Genomic-based new classifications are essential to distinguish the progressing from non-progressing oral precancers. The proposed research aims to determine genome-wide differential allelic imbalance (LOH) profiles for progressing and non-progressing oral precancers. Specific Aim 1 is to establish and optimize a series of innovative emerging genomic tools, to be used consecutively for the application on oral precancers in vivo. This will be accomplished during the Scholar Development Phase (2 years). Specific Aim 2, to be performed in the Faculty Transition Phase, is to determine the genome wide LOH profiles in progressing and non-progressing oral precancers and generate molecular classification for the prediction of oral precancer progression. Specific Aim 3 is to identify candidate genes for oral precancer progression in the identified LOH regions. Functional and biological tests are in place to evaluate the functional contribution of candidate genes to the tumor progression process. A career development plan is in place to prepare the candidate for translational head and neck cancer research. Defined and evaluative milestones are in place to assess the scientific progress of the candidate, particularly during transition to the Faculty Transition Phase. In addition to the research training, the candidate will receive didactic training in bioethics and responsible conduct of research, oral pathology, biostatistics, and grant writing. The outcome of this award will be a well prepared and competitive young scientist committed to a career in translational head and neck cancer research.

描述(申请人提供)：本次K22申请是为了支持周晓峰博士成为头颈癌研究领域的独立研究员进行学术培训和职业发展。这份申请详细说明了这项建议在候选人、导师、职业发展计划、环境和研究计划方面的优势和独特性。 这项拟议的研究是为了检验这样一个假设，即存在区分进展性和非进展性口腔癌前病变的基因组决定因素。所有级别的口腔癌前病变恶变的总体风险约为18%。根据传统的临床和组织学特征，不可能预测任何一种病变的进展。基于基因组的新分类对于区分进展期和非进展期口腔癌前病变是必不可少的。这项拟议的研究旨在确定进展性和非进展性口腔癌前病变的全基因组差异等位基因失衡(LOH)谱。具体目标1是建立和优化一系列创新的新兴基因组工具，以便连续用于口腔癌前病变的活体应用。这将在学者发展阶段(2年)完成。将在教师过渡阶段执行的特定目标2是确定进展期和非进展期口腔癌前病变的全基因组LOH谱，并产生用于预测口腔癌前病变进展的分子分类。具体目标3是在已确定的LOH区域中确定口腔癌前病变进展的候选基因。功能和生物学测试已经到位，以评估候选基因对肿瘤进展过程的功能贡献。 职业发展计划已经就位，为转化型头颈癌研究做准备。有明确的和评估的里程碑，以评估候选人的科学进步，特别是在过渡到教师过渡阶段期间。除了研究培训，候选人还将接受生物伦理学和负责任的研究、口腔病理学、生物统计学和拨款撰写方面的教学培训。这一奖项的结果将是一位准备充分、有竞争力的年轻科学家，他致力于转化头颈部癌症研究。

项目成果

MicroRNA-222 regulates cell invasion by targeting matrix metalloproteinase 1 (MMP1) and manganese superoxide dismutase 2 (SOD2) in tongue squamous cell carcinoma cell lines.

• 发表时间: 2009-05
• 期刊: Cancer genomics & proteomics
• 影响因子: 2.5
• 作者: Xiqiang Liu;Jinsheng Yu;Lu Jiang;Anxun Wang;Fei Shi;Hui Ye;Xiaofeng Zhou

Allelic imbalance analysis of oral tongue squamous cell carcinoma by high-density single nucleotide polymorphism arrays using whole-genome amplified DNA.

使用全基因组扩增 DNA 通过高密度单核苷酸多态性阵列对口腔舌鳞状细胞癌进行等位基因不平衡分析。

• DOI: 10.1007/s00439-005-0069-x
• 发表时间: 2005
• 期刊: Human genetics
• 影响因子: 5.3
• 作者: Zhou,Xiaofeng;Temam,Stephane;Chen,Zugen;Ye,Hui;Mao,Li;Wong,DavidTW
• 通讯作者: Wong,DavidTW

Proteomic based identification of manganese superoxide dismutase 2 (SOD2) as a metastasis marker for oral squamous cell carcinoma.

• 发表时间: 2008-03
• 期刊: Cancer genomics & proteomics
• 影响因子: 2.5
• 作者: Hui Ye;Anxun Wang;Bao-shiang Lee;Tianwei Yu;Shihu Sheng;Tingsheng Peng;Shen Hu;D. Crowe;Xiaofeng Zhou

MicroRNA profiling and head and neck cancer.

• DOI: 10.1155/2009/837514
• 发表时间: 2009
• 期刊: Comparative and functional genomics
• 作者: Liu X;Chen Z;Yu J;Xia J;Zhou X
• 通讯作者: Zhou X

Downregulation of the Rho GTPase signaling pathway is involved in the microRNA-138-mediated inhibition of cell migration and invasion in tongue squamous cell carcinoma.

• DOI: 10.1002/ijc.25320
• 发表时间: 2010-08-01
• 期刊: INTERNATIONAL JOURNAL OF CANCER
• 影响因子: 6.4
• 作者: Jiang, Lu;Liu, Xiqiang;Kolokythas, Antonia;Yu, Jinsheng;Wang, Anxun;Heidbreder, Caroline E.;Shi, Fei;Zhou, Xiaofeng
• 通讯作者: Zhou, Xiaofeng