DEVELOPMENT AND VALIDATION OF PROGNOSTIC MODEL FOR GASTRIC CANCER

描述(申请人提供)：胃癌(GC)是世界上最致命的癌症之一。全球每年有超过93万人被诊断为GC，70万人死亡(第二大死因)。局限性胃癌患者最常接受手术治疗(在亚洲)或手术加辅助治疗(北美)。这一治疗决定是经验性的。没有方法可以选择特定的疗法或避免特定的疗法。因此，几乎所有AJCC/UICC II或III期癌症患者都得到了类似的治疗，但他们的结果是不可预测的。我们有相当多的初步数据表明，所有病理阶段基于聚合酶链式反应的实用预后标志(允许我们计算连续的“风险”评分)是可能的。我们的主要目标是开发一种基于聚合酶链式反应的生物标记物预后测试，以预测接受手术或不接受辅助治疗的局部胃癌患者的早期(=12个月)无复发生存(RFS)事件。如果新出现的预后征象具有很高的准确率(=80%)，可以开发替代策略来优化治疗。目前，我们不能优化治疗，最终对所有阶段相似的患者给予相同的治疗。我们的总体目标是在更大的独立亚洲GC患者队列和西方GC患者队列中验证先前识别的预后基因签名，并通过识别更多的生物标记物来构建更好的预后签名和风险评分来提高签名的可预测性。 公共卫生相关性：这项建议的总体目标是开发新的预后风险评分，可以预测胃癌患者早期复发的可能性。我们的方法将为根据患者的相对风险优化患者的治疗铺平道路。目前，我们不能优化治疗，最终对所有阶段相似的患者给予相同的治疗。

DESCRIPTION (provided by applicant): Gastric cancer (GC) is one of the most virulent cancers in the world. Each year over 930,000 of people are diagnosed with GC and 700,000 die (2nd leading cause of death) worldwide. Patients with localized gastric cancer are most often treated surgery alone (in Asia) or surgery plus adjunct therapy (North America). This decision for treatment is empiric. There is no method to select a specific therapy or to avoid a specific one. Therefore, nearly all patients with AJCC/UICC stage II or III cancer are offered a similar treatment but their outcomes are unpredictable. We have considerable preliminary data that suggests a PCR-based practical prognostic signature (that allows us to compute a continuous "risk" score) for all pathologic stages is possible. Our main objective is to develop a PCR-based biomarker prognostic test for an "early" (= 12 months) recurrence-free survival (RFS) event for localized gastric cancer patients who undergo surgery with or without adjunct therapy. If the emerging prognostic signature has a high rate of accuracy (= 80%), alternate strategies can be developed to optimize treatment. Currently, we cannot optimize therapy and end up giving the same therapy to all patients with similar stage. Our overall goal is to validate previously identified prognostic gene signature in larger independent Asian GC patient cohort and Western GC patient cohorts, and improve the predictability of signatures by identifying more biomarkers to construct better prognostic signature and risk score. PUBLIC HEALTH RELEVANCE: The overall goal of this proposal is to develop novel prognostic risk score that can predict the likelihood of early recurrence in gastric cancer patients. Our approach will pave the way for the optimization of patient treatments according to relative risk of patients. Currently, we cannot optimize therapy and end up giving the same therapy to all patients with similar stage.