Strategy for the Incorporation of Tissue Biomarkers in the Clinical Management of

将组织生物标志物纳入临床管理的策略

• 批准号: 7962011
• 负责人: RUSSELL R BROADDUS
• 金额: $ 20.73万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7962011
• 关键词: Adjuvant Therapy; Adopted; Autophagocytosis; Binding Proteins; Biological Assay; Biological Markers; Biology; Biopsy; Cancer Center; Cancer Patient; Carcinoma; Caring; Clinic; Clinical; Clinical Management; Comorbidity; Data Set; Decision Making; Diabetes Mellitus; Diagnosis; Diagnostic; Diagnostic Neoplasm Staging; Disease; Doctor of Medicine; Endometrial; Endometrial Carcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrioid Carcinoma; Endometrium; Estrogen receptor positive; Estrogens; Evaluation; Fingerprint; Formalin; Fostering; Funding; Gene Expression; Genes; Genomics; Goals; Growth; Guidelines; High Risk Woman; Hypertension; Hysterectomy; In Vitro; Incidence; Insulin-Like Growth Factor I; Knowledge; Light; Lymph node excision; Malignant Neoplasms; Mesenchymal; Methodology; Modeling; Molecular; Obesity; Oncologist; Operative Surgical Procedures; Paraffin Embedding; Pathway interactions; Patient Care; Patients; Pelvis; Phase; Physicians; Positive Lymph Node; Postoperative Period; Protein Binding; Proteins; Quantitative Reverse Transcriptase PCR; Radiation therapy; Receiver Operating Characteristics; Recurrence; Reproduction spores; Research; Risk; Sampling; Series; Site; Specimen; Staging; Surgical Management; Techniques; Technology; Testing; Tissue Sample; Tissues; Translational Research; Tretinoin; Universities; University of Texas M D Anderson Cancer Center; Vagina; Validation; Vent; Washington; Woman; Work; base; chemotherapy; clinical care; clinical practice; follow-up; high risk; improved; innovation; kidney vascular structure; leukemia; malignant breast neoplasm; molecular marker; mortality; novel; outcome forecast; prevent; programs; protein degradation; repository; routine care; standard of care; tissue fixing; tool; tumor

Crucial gaps in knowledge prevent the providing of ideal individualized care to women with endometrial cancer. The extent of lymphadenectomy and the identification of which patients would benefit the most from complete surgical staging are unresolved clinical issues. A second important gap is the ability to predict which women with low stage endometrioid-type endometrial cancer will suffer recurrence. We have used genomic approaches to identify tissue biomarkers of endometrial cancer. These biomarkers have been validated in a large set of endometrial cancers at MDACC, and we have documented their close association with stage and recurrence. Next, we will validate these findings in independent data sets. We hypothesize that quantifying genes associated with EMT and estrogen's growth regulatory actions in the endometrium as a "biomarker score" will provide a clinically useful tool to assist in the decision to perform complete surgical staging on women diagnosed with endometrial cancer and will predict which women with stage I and stage II endometrioid carcinomas will recur. In Aim 1, we will validate the association of our biomarkers with endometrial cancer stage in an independent data set obtained from a series of patients who unden/vent comprehensive surgical staging at the Mayo clinic. We will also establish that the biomarker score computed from formalin-fixed, paraffin-embedded endometrial biopsies is a good approximation of the same scores based on tissue from the final hysterectomy. We will determine the association of the biomarker panel with endometrioid carcinoma recurrence in independent data sets obtained from Mayo Clinic and Washington University. In Aim 2, reverse phase protein lysate array (RPPA) will be used to identify proteins and phospho-proteins that are associated with endometrioid carcinoma stage. These newly identified biomarkers will be used to augment our currently existing panel. We will also develop methodology to perform RPPA using formalin-fixed tissues so that this technology becomes more relevant to clinical samples. Finally RPPA will be used to help identify proteins that interact with EIG121, one of the more exciting but least understood biomarkers in our existing panel.

知识上的关键差距阻碍了为子宫内膜异位症妇女提供理想的个性化护理 癌淋巴结切除的范围和确定哪些患者将受益最多 完整的手术分期是尚未解决的临床问题。第二个重要的差距是预测能力 患有低阶段类性腺型子宫内膜癌的妇女将遭受复发。我们已经使用 基因组方法来鉴定子宫内膜癌的组织生物标志物。这些生物标志物已经被 在MDACC的大量子宫内膜癌中得到验证，我们已经证明了它们之间的密切联系 分期和复发接下来，我们将在独立数据集中验证这些发现。我们假设 量化子宫内膜中与EMT和雌激素生长调节作用相关的基因， "生物标记物评分"将提供临床上有用的工具，以帮助决定是否进行完整的外科手术， 对诊断为子宫内膜癌的妇女进行分期，并预测哪些妇女患有I期和II期子宫内膜癌。 类胶质瘤会复发。在目标1中，我们将验证我们的生物标志物与 子宫内膜癌分期在一个独立的数据集，从一系列的患者谁unden/vent 在马约诊所进行全面的手术分期。我们还将确定计算的生物标志物评分 福尔马林固定石蜡包埋的子宫内膜活检组织中， 根据最后一次子宫切除的组织我们将确定生物标志物组与 从马约诊所和华盛顿获得的独立数据集中的类胶质瘤复发 大学在目标2中，反相蛋白裂解物阵列（RPPA）将用于鉴定蛋白质， 与类甲状腺癌阶段相关的磷蛋白。这些新发现的生物标志物 将被用来扩充我们现有的小组我们还将制定执行RPPA的方法 使用福尔马林固定的组织，使得该技术变得与临床样品更相关。最后 RPPA将用于帮助识别与EIG121相互作用的蛋白质，这是一种更令人兴奋但最不重要的蛋白质。 了解我们现有小组中的生物标志物。