Biomarkers of survival in glioma epidemiology

神经胶质瘤流行病学中的生存生物标志物

基本信息

批准号：
7934298
负责人：
John K. Wiencke
金额：
$ 46.45万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-07-01 至 2011-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7934298
关键词：
Abbreviations Address Adult Adult Glioma Area Asthma Biological Assay Biological Markers Biopsy Blood Brain Neoplasms CCR CD14 gene California Cancer Center Caring Case Series Case-Control Studies Characteristics Clinic Clinical Clinical Investigator Clinical Research Clinical Trials Clinical trial protocol document Collaborations Confidence Intervals Confusion Country Data Data Set Diagnosis Disease Enrollment Epidemiology Epidermal Growth Factor Receptor Evaluation Excision Family Formalin Funding Genes Genetic Genetic Polymorphism Genetic Transcription Genotype Glioblastoma Glioma Goals Grant HLA Antigens Haplotypes Hypersensitivity IL13RA1 gene IL4 gene IL4R gene IgE Immune Immunoglobulins Immunohistochemistry Inflammation Mediators Interleukin-13 Interleukins Intervention Investigation Karnofsky Performance Status Laboratories Low affinity IgE receptor Malignant Neoplasms Measures Medicine Methylation Molecular Mutation Names Neuraxis Newly Diagnosed O(6)-Methylguanine-DNA Methyltransferase Paraffin Embedding Parents Patient Recruitments Patients Pharmaceutical Preparations Prognostic Marker Proteins Public Health Questionnaires Radiation Radiation Therapy Oncology Group Recruitment Activity Reproduction spores Research Research Personnel Resources SEER Program San Francisco Series Serological Serum Serum Markers Single Nucleotide Polymorphism Source Specialized Program of Research Excellence Specimen Stratification Subgroup TP53 gene Time Treatment Factor Tumor Markers Tumor Tissue Universities Validation Vital Status Work base case control chemotherapy hazard improved innovation mRNA Expression medical specialties neoplasm registry neuro-oncology novel oncology service outcome forecast population based prognostic programs public health relevance receptor response temozolomide tumor validation studies

项目摘要

DESCRIPTION (provided by applicant): To address the great need for improved therapies for adult glioma, this project will evaluate molecular features of tumor tissue, serologic immune factors and genetic polymorphisms as biomarkers of patient surival. The proposed studies are additions to ongoing recruitment of patients in a 16 year R01 funded population-based case control study and 5 years of SPORE funded clinic-based research in the UCSF Neuro-oncology Clinic (NOC). Together these sources provide among the country s largest datasets of well-characterized adult glioma patients with polymorphism, serologic, tumor marker, demographic and other epidemiologic, treatment, and survival data. We will continue to determine vital status and relevant treatment information for population based adult onset glioma cases diagnosed 1997-99 and 2001-04 and patients accrued through the UCSF NOC 2002-2006 (total number ~1500) and (b) accrue ~720 patients (questionnaire, blood, buccal, and tumor specimens) in the UCSF NOC 2007-2011. (Another population based series to begin May 2006 will bring the total number of patients diagnosed from 2006-2011 to ~960). Several biomarkers identified in our ongoing and other studies warrant further research. In Aims 1,2 of this proposal we will obtain a greater understanding of the mechanisms of improved survival among glioblastoma cases with elevated versus normal or borderline serum IgE levels observed in our current series and validate and expand findings to other potentially related serum markers (sCD23 and sCD14), tumor markers (CD23 protein and IL13RA2 mRNA expression), and constitutive SNPs in IL4, IL13, IL4R, IL13RA1, and IL13RA2. These markers will also be assessed in relation to tumor TP53 mutation and expression and EGFR amplification and expression (markers measured in the parent R01 study). In Aim 3 we will determine whether polymorphisms in MGMT or tumor TP53 mutation or expression influence survival in the presence or absence of tumor MGMT methylation in patients treated or not treated with temozolomide. In Aim 4 we will validate promising markers obtained from Aims 2 and 3 in newly diagnosed patients seen at the UCSF NOC from July 1, 2007-June 30, 2011 in ~120 of these GM cases on clinical trial protocols. Identification of predictive biomarkers related glioma survival is likely to aid in choosing the best treatments for each glioma patient, in enhancing definition of homogeneous subgroups for clinical trials based on uniform prognosis for rapid treatment evaluation, and in providing better prognostic information to patients. PUBLIC HEALTH RELEVANCE: The proposed study will help identify markers that may be useful in the treatment of adult glioma brain tumors. Specific therapies may be more effective in some patient groups that display specific genetic, immulogical, and tumor characteristics. The relevance of individualizing brain tumor treatment to public health and cancer medicine lies in sparing patients ineffective and potentially toxic therapies while guideing newer experimental treatments to those patients who may benefit the most from such interventions.

描述（由申请人提供）：为了满足改善成人神经胶质瘤疗法的巨大需求，该项目将评估肿瘤组织的分子特征，血清学免疫因子和遗传多态性，作为患者临床的生物标志物。拟议的研究是在16年R01资助的基于人群的病例对照研究中持续招募患者的补充，以及在UCSF神经肿瘤学诊所（NOC）中基于孢子的5年基于孢子的基于诊所的研究。这些来源共同提供了具有多态性，血清学，肿瘤标记，人口统计学和其他流行病学，治疗和生存数据的良好表征成人神经胶质瘤患者的最大数据集。 We will continue to determine vital status and relevant treatment information for population based adult onset glioma cases diagnosed 1997-99 and 2001-04 and patients accrued through the UCSF NOC 2002-2006 (total number ~1500) and (b) accrue ~720 patients (questionnaire, blood, buccal, and tumor specimens) in the UCSF NOC 2007-2011. （2006年5月开始的另一个基于人群的系列将使2006 - 2011年诊断为诊断的患者总数达到〜960）。我们正在进行的研究和其他研究中确定的几种生物标志物值得进一步研究。在该提案的目标1,2中，我们将对胶质母细胞瘤病例中提高生存的机制有更深入的了解，这些病例的生存机制升高，与正常或边界血清或边界血清IgE水平升高，并在我们当前的系列中观察到，并验证并将发现和扩展到其他潜在相关的血清标记物（SCD23和SCD14）（SCD23和SCD14），肿瘤标志物（CD23蛋白和cont prount and conts in in in il13 prount and iil133333333333 prom in iil1333333 prot in in iil133333 prot in。 IL13，IL4R，IL13RA1和IL13RA2。这些标记也将根据肿瘤TP53突变和表达以及EGFR扩增和表达评估（在父R01研究中测量）。在AIM 3中，我们将确定MGMT或肿瘤TP53突变中的多态性或表达是否在存在或不接受替莫唑胺治疗的患者的肿瘤MGMT甲基化的情况下会影响存活。在AIM 4中，我们将验证从AIMS 2和3获得的有希望的标记，从2007年7月1日至2011年7月30日在UCSF NOC中看到的新诊断的患者在临床试验方案中的这些GM案例中有约120例。鉴定预测生物标志物相关的神经胶质瘤存活率可能有助于为每位神经胶质瘤患者选择最佳治疗方法，以增强基于均匀预后的临床试验的同质亚组的定义，以快速治疗评估，并为患者提供更好的预后信息。公共卫生相关性：拟议的研究将有助于确定可能在治疗成人神经胶质瘤脑肿瘤的标志物。在某些表现出特定遗传，免疫和肿瘤特征的患者组中，特定疗法可能更有效。个性化脑肿瘤治疗与公共卫生和癌症医学的相关性在于保留患者无效且潜在的有毒疗法，同时指导那些可能从这种干预措施中受益最大的患者的新实验疗法。