Transcriptomic classification of non-muscle invasive bladder cancer and its clinical and prognostic implication
非肌层浸润性膀胱癌的转录组学分类及其临床和预后意义
基本信息
- 批准号:10693811
- 负责人:
- 金额:$ 128.98万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-01 至 2027-08-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAddressAdjuvant TherapyAdverse effectsBCG LiveBacillus Calmette-Guerin TherapyBiological AssayCancer PatientClassificationClinicalClinical ManagementConsensusDataDemographic FactorsDiagnosisDiseaseEarly treatmentEthnic OriginEtiologyEventFailureGenerationsGenesGoalsHealthcare SystemsHeterogeneityImmuneIndividualIntravesical AdministrationInvestigationKnowledgeLife StyleMalignant NeoplasmsMalignant neoplasm of urinary bladderModelingMolecularMolecular ProfilingMuscleNatureNewly DiagnosedOccupationalOutcomePathologicPatient-Focused OutcomesPatientsProspective cohortRaceRecurrenceRecurrent Malignant NeoplasmRecurrent diseaseResearchResearch PriorityRiskRisk FactorsSample SizeSmokingSpecimenSurvival RateSystemTaxonomyTherapeuticTranslatingTranslationsTreatment outcomeTumor SubtypeValidationaggressive therapycancer carecancer epidemiologycancer heterogeneitycancer recurrencecancer subtypesclinical careclinical practiceclinical translationcohortcosteffective therapyenvironmental chemical exposurefollow-uphealth care deliveryhigh riskimmunogenicimprovedindividualized medicineintravesicalmeetingsmolecular markermolecular subtypesnano-stringnon-muscle invasive bladder cancerpopulation basedpredicting responsepredictive modelingpredictive toolspreventprimary outcomeprognosticprognostic valueresponserisk prediction modelrisk stratificationsextooltranscriptometranscriptomicstreatment responsetumortumor progression
项目摘要
This study addresses the unmet clinical needs for management of non-muscle invasive bladder cancer
(NMIBC). NMIBC represents ~75% of bladder cancer cases and has a favorable five-year survival rate, but
typically recurs (50-70% in 5 years) and progresses to muscle-invasive disease (MIBC, 10-30%). Intravesical
Bacillus Calmette-Guerin (BCG) is the most effective therapy to prevent NMIBC recurrence and progression,
yet BCG has a 30% failure rate, with various adverse effects leading to intolerance. Two critical needs exist: 1)
a risk stratification tool to identify patients at high risk of recurrence and progression for early and aggressive
treatment, and 2) a response prediction tool to identify patients who are unresponsive or intolerant to BCG for
other treatment options. Our goal is to develop and validate risk-stratification and BCG-response tools by
incorporating molecular signatures into the current pathological system for optimal clinical care of NMIBC.
Transcriptome analysis is powerful to identify genes, and importantly, to define cancer molecular subtypes
associated with different therapeutic and prognostic outcomes. This approach has been applied in bladder
cancer but primarily focused on MIBC. Research on NMIBC is an unmet need. Building on the Bladder Cancer
Epidemiology, Wellness, and Lifestyle Study (Be-Well), one of the largest prospective cohorts of NMIBC
patients, we propose to conduct a comprehensive transcriptomic analysis of NMIBC and examine the utility of
molecular subtypes with additional prognostic genes in predicting NMIBC treatment response and prognostic
outcomes. Our central hypothesis is that molecular signatures (i.e., molecular subtypes and/or other
genes) could unveil NMIBC heterogeneity and thus improve the current pathological classification
system for tailored NMIBC care. We will: Aim 1. Develop a risk stratification tool for NMIBC prognostic
outcomes by incorporating molecular subtypes, genes, clinicopathological and demographic factors. Primary
outcomes will be disease recurrence and progression, with survival explored. We will define molecular
subtypes and identify genes by NMIBC prognostic outcomes (1a), build risk prediction models in Be-Well
(n=928) (1b), validate molecular signatures and the risk-stratification tool in an independent validation cohort
(n=959) (1c), and explore the tool in sex and race specific groups in the pooled cohorts (1d). Aim 2. Develop a
response prediction tool for BCG outcomes by incorporating molecular subtypes, immune signatures, genes,
clinicopathological and demographic factors. Primary outcomes will be BCG unresponsive with BCG intolerant
explored. Given the high immunogenic nature of bladder cancer and BCG therapy, we will develop the BCG-
response prediction tool with further consideration of immune signatures in patients who received BCG in Be-
Well (n=426) and a validation cohort (n=691). We will explore characterization of molecular subtypes by sex,
race/ethnicity, and etiological risk factors. Clinical translation will be accelerated given the generation of
NMIBC-specific molecular signatures using NanoString in a large health care delivery system setting.
本研究旨在解决非肌肉浸润性膀胱癌治疗的临床需求
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Marilyn L Kwan其他文献
Marilyn L Kwan的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Marilyn L Kwan', 18)}}的其他基金
Impact of Body Composition and Related Inflammatory and Immune States on Prognosis of Non-Muscle Invasive Bladder Cancer
身体成分及相关炎症和免疫状态对非肌肉浸润性膀胱癌预后的影响
- 批准号:
10674401 - 财政年份:2023
- 资助金额:
$ 128.98万 - 项目类别:
Transcriptomic classification of non-muscle invasive bladder cancer and its clinical and prognostic implication
非肌层浸润性膀胱癌的转录组学分类及其临床和预后意义
- 批准号:
10388707 - 财政年份:2022
- 资助金额:
$ 128.98万 - 项目类别:
Lifestyle and Molecular Factors of Bone Health in Breast Cancer Survivors
乳腺癌幸存者的生活方式和骨骼健康的分子因素
- 批准号:
8539751 - 财政年份:2012
- 资助金额:
$ 128.98万 - 项目类别:
Lifestyle and Molecular Factors of Bone Health in Breast Cancer Survivors
乳腺癌幸存者的生活方式和骨骼健康的分子因素
- 批准号:
8688963 - 财政年份:2012
- 资助金额:
$ 128.98万 - 项目类别:
Lifestyle and Molecular Factors of Bone Health in Breast Cancer Survivors
乳腺癌幸存者的生活方式和骨骼健康的分子因素
- 批准号:
8399485 - 财政年份:2012
- 资助金额:
$ 128.98万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 128.98万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 128.98万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 128.98万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 128.98万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 128.98万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 128.98万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 128.98万 - 项目类别:
EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 128.98万 - 项目类别:
Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 128.98万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 128.98万 - 项目类别:
Research Grant