Multidiciplinary Integrative Genomic Approach to Distinguish Lethal from Indolent Prostate Cancer in Men of Europena and African Ancestry

多学科综合基因组方法区分欧洲和非洲血统男性的致命性前列腺癌和惰性前列腺癌

• 批准号: 10253255
• 负责人: ANGELO Michael DE MARZO
• 金额: $ 64.84万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-10 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10253255
• 关键词: Address; Advocate; African; African American; Aging; Algorithms; American; Architecture; Automobile Driving; Autopsy; Baltimore; Bioinformatics; Biological Markers; Biometry; Biopsy; Cancer Etiology; Cancer Patient; Categories; Cessation of life; Clinical; Clinical Management; Collaborations; Collection; Coupled; DNA Methylation; DNA Sequence Rearrangement; DNA sequencing; Data Analyses; Data Set; Databases; Development; Diagnosis; Disease; Epidemiology; Equilibrium; Expression Profiling; Follow-Up Studies; Freezing; Frequencies; Genomic approach; Genomics; Gleason Grade for Prostate Cancer; Health; Health Professional; Immunohistochemistry; In Situ; In Situ Hybridization; Individual; Indolent; Intervention; Kinetics; Lesion; Localized Malignant Neoplasm; Longitudinal Studies; Longterm Follow-up; Malignant Neoplasms; Malignant neoplasm of prostate; Medical Oncology; Messenger RNA; Methods; Modernization; Molecular; Molecular Biology; Molecular Profiling; Monitor; Mutation; Nature; Neoplasm Metastasis; Nomograms; Organ; Outcome; PSA screening; Pathologic; Pathology; Pathway interactions; Patient Care; Patient-Focused Outcomes; Patients; Phase; Phenotype; Physicians; Population; Progressive Disease; Prostate Adenocarcinoma; Race; Radical Prostatectomy; Recurrence; Research Personnel; Resources; Risk; Risk stratification; Screening for Prostate Cancer; Sum; Technology; Testing; Therapeutic Intervention; Urology; Validation; Variant; Visceral; Work; base; biobank; cancer therapy; caucasian American; cell type; cohort; computer science; design; epigenomics; exome sequencing; experience; genome sequencing; genome-wide; improved; interdisciplinary approach; men; minimally invasive; mortality; multidisciplinary; multimodality; neoplastic cell; next generation; novel; novel marker; outcome forecast; outcome prediction; overtreatment; predictive signature; prostate cancer risk; public health relevance; racial disparity; screening; tool; transcriptome sequencing; treatment strategy; tumor; unnecessary treatment; whole genome

 DESCRIPTION (provided by applicant): There are several critical unmet needs in the management of localized prostate cancer. Central among them is the development of minimally invasive tools to distinguish localized cancers that are truly indolent from cancers that are progressive and potentially lethal. To address this key need, we first propose to perform an integrated, multi-dimensional genomic, epigenomic and expression analysis to uncover novel molecular pathways that characterize indolent vs. aggressive prostate cancers. In this approach we define indolent tumors as those screen detected (e.g. PSA screening) lesions that are Gleason score 6 (or less) that are organ confined at radical prostatectomy. We consider these tumors indolent as they do not appear capable of metastasis. In contrast, we equate Gleason score 8-10 tumors as "interval" or symptomatic since, even with primary treatment, these tumors often recur and metastasize at high frequencies. Additionally, we will validate our key markers/pathways discovered in this project using additional populations with long term outcomes. We hypothesize that our multi-modality genomic-based integrated approach, contrasting these two divergent tumor types, will reveal signatures that distinguish cancers with dichotomous phenotypes. We also hypothesize that these signatures will vary based on race and thus in parallel we will comprehensively characterize African American prostate cancers to reveal molecular features driving racial disparities in outcomes. We will validate the signatures obtained using large cohorts of cases with established outcomes including: (1) the Johns Hopkins Active surveillance cohort and (2) Prostate cancer cases from the BLSA (Baltimore Longitudinal Study of Aging), an observational cohort of men followed since 1954 with autopsy documented indolent or aggressive/lethal disease. We also propose that these signatures will be able to predict outcomes of cancers with indeterminate kinetics and propose to test this through analysis of cases of intermediate risk prostate cancer with long-term follow-up and known outcomes from Johns Hopkins and in collaboration with colleagues from Harvard, from the Physician's Health and Health Professionals follow-up studies. Together this work will yield highly relevant information that can be directly applied to the clinical management of localized prostate cancer. Specifically, it will yield an integrated signature that distinguishes localized - indolent tumors from localized tumors with lethal potential. Additionally we believe these signatures will be critical in determining treatment strategies for individuals with prostate cancers of indeterminate kinetics.



项目成果

Transcriptional landscape of PTEN loss in primary prostate cancer.

• DOI: 10.1186/s12885-021-08593-y
• 发表时间: 2021-07-26
• 期刊: BMC cancer
• 影响因子: 3.8
• 作者: Imada EL;Sanchez DF;Dinalankara W;Vidotto T;Ebot EM;Tyekucheva S;Franco GR;Mucci LA;Loda M;Schaeffer EM;Lotan T;Marchionni L
• 通讯作者: Marchionni L

Contemporary Incidence and Outcomes of Prostate Cancer Lymph Node Metastases.

• DOI: 10.1016/j.juro.2017.12.048
• 发表时间: 2018-06
• 期刊: The Journal of urology
• 作者: Bernstein AN;Shoag JE;Golan R;Halpern JA;Schaeffer EM;Hsu WC;Nguyen PL;Sedrakyan A;Chen RC;Eggener SE;Hu JC
• 通讯作者: Hu JC

Correlation of B7-H3 with androgen receptor, immune pathways and poor outcome in prostate cancer: an expression-based analysis.

B7-H3与雄激素受体，免疫途径和前列腺癌预后不良的相关性：基于表达的分析。

• DOI: 10.1038/pcan.2016.49
• 发表时间: 2017-03
• 期刊: Prostate cancer and prostatic diseases
• 影响因子: 4.8
• 作者: Benzon B;Zhao SG;Haffner MC;Takhar M;Erho N;Yousefi K;Hurley P;Bishop JL;Tosoian J;Ghabili K;Alshalalfa M;Glavaris S;Simons BW;Tran P;Davicioni E;Karnes RJ;Boudadi K;Antonarakis ES;Schaeffer EM;Drake CG;Feng F;Ross AE
• 通讯作者: Ross AE

Use of the Prostate Health Index for detection of prostate cancer: results from a large academic practice.

• DOI: 10.1038/pcan.2016.72
• 发表时间: 2017-06
• 期刊: Prostate cancer and prostatic diseases
• 影响因子: 4.8
• 作者: Tosoian JJ;Druskin SC;Andreas D;Mullane P;Chappidi M;Joo S;Ghabili K;Agostino J;Macura KJ;Carter HB;Schaeffer EM;Partin AW;Sokoll LJ;Ross AE
• 通讯作者: Ross AE

Risk of Pathological Upgrading and Up Staging among Men with Low Risk Prostate Cancer Varies by Race: Results from the National Cancer Database.

患有低风险前列腺癌的男性病理升级和上台的风险因种族而有所不同：国家癌症数据库的结果。

• DOI: 10.1016/j.juro.2016.08.095
• 发表时间: 2017-03
• 期刊: The Journal of urology
• 作者: Maurice MJ;Sundi D;Schaeffer EM;Abouassaly R
• 通讯作者: Abouassaly R