Development of Metabolomic and Molecular Probes for Prostate Cancer Assessment

用于前列腺癌评估的代谢组学和分子探针的开发

基本信息

批准号：
8332771
负责人：
Leo L Cheng
金额：
$ 18.93万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-14 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8332771
关键词：
Adjuvant Therapy Age Aggressive behavior Benign Prostatic Hypertrophy Biochemical Biological Biological Assay Biopsy Cancer Patient Caring Cells Citrates Clinic Clinical Clinical Protocols Complex Data Degradation Pathway Development Diagnosis Diagnostic Early Diagnosis Engineering Enzymes Evaluation Gleason Grade for Prostate Cancer Growth Human Hyperplasia Individual Indolent Knowledge Lead Life Magnetic Resonance Spectroscopy Malignant Neoplasms Malignant neoplasm of prostate Measurement Measures Messenger RNA Metabolic Metabolism Methods Modality Molecular Molecular Biology Molecular Probes Molecular Profiling Morphology Pathological Staging Pathology Pathway interactions Patients Personal Satisfaction Polymerase Chain Reaction Prostate Prostate Adenocarcinoma Prostate-Specific Antigen Prostatectomy Prostatic Intraepithelial Neoplasias Prostatic Neoplasms Proteins Publishing Quality of life Recurrence Screening for cancer Screening procedure Serum Specimen Spermine Staging Survival Rate System Testing Time Tissues Work Zinc base cancer prevention cancer recurrence clinically significant cost insight laser capture microdissection latent prostate cancer metabolomics outcome forecast patient population preclinical study success tool tumor uptake

项目摘要

DESCRIPTION (provided by applicant): The development of PSA testing for prostate cancer (PCa) resulted in rising diagnoses of early latent PCa that may not become clinically significant in a patient's lifetime. Unfortunately, a lack of clinical capability to identify these cases often leads to aggressive treatments that unnecessarily reduce the quality of life for this large patient population. Tools that can measure PCa growth rate and aggressiveness are urgently needed to facilitate the precise and accurate differentiation of relatively indolent tumors from more threatening ones at different stages of care to benefit the well-being of the patients and reduce costs of care on the whole. Based on published data and our preliminary results, this project will test the hypothesis that PCa growth and aggression potential may be evaluated through measurement of spermine and citrate levels with intact-tissue magnetic resonance spectroscopy (MRS) and quantification of the expression levels of mRNAs in the spermine synthesis/degradation and zinc-citrate complex pathways with real-time quantitative (rt-q) PCR for different pathological components obtained from laser capture microdissection (LCM). Specifically, we will measure correlations of PCa growth rates with metabolomic profiles, spermine and citrate concentrations according to quantitative pathology, and with expression levels of mRNAs for enzymes in the spermine synthesis/degradation pathways and zinc uptake protein, hZIP1, for different pathological components isolated with LCM from patients of clinically proven benign prostatic hyperplasia (BPH), prostatrophic hyperplasia (PAH), prostatic intraepithelial neoplasm (PIN), and different grades of prostate adenocarcinomas (PCa), all with reliable PSA velocity (Vpsa) calculated from multiple PSA results over time. We will retrospectively measure correlations of PCa aggressiveness with these measured biological parameters for age-, Gleason-score- (GS), pathological-stage-, and adjuvant-therapy-matched PCa patients with and without cancer biochemical recurrence (BCR) after prostatectomies. Success of the studies will enable us to establish a biochemical diagnostic system for PCa that expands the current morphology-based pathology to include information on tumor metabolism and molecular biology. These results will help clinicians assess bioactivity in specific tumors, determine patient prognosis, and select the most appropriate therapy for individual patients and contribute profound understanding of human malignancy and provide new insights into possible new directions for cancer prevention, diagnosis, and treatment.

描述（由申请人提供）：前列腺癌 (PCa) PSA 检测的发展导致早期潜伏性 PCa 的诊断率上升，而这些早期潜伏性 PCa 在患者的一生中可能不会变得具有临床意义。不幸的是，缺乏识别这些病例的临床能力往往会导致积极的治疗，从而不必要地降低大量患者的生活质量。迫切需要能够测量 PCa 生长速度和侵袭性的工具，以促进在不同护理阶段精确地区分相对惰性的肿瘤和更具威胁性的肿瘤，从而有利于患者的福祉并降低整体护理成本。根据已发表的数据和我们的初步结果，该项目将测试以下假设：可以通过使用完整组织磁共振波谱 (MRS) 测量精胺和柠檬酸盐水平以及对 PCa 中 mRNA 表达水平进行定量来评估 PCa 生长和攻击潜力。通过实时定量 (rt-q) PCR 分析精胺合成/降解和柠檬酸锌复合物途径，以检测从激光捕获显微切割 (LCM) 获得的不同病理成分。具体来说，我们将根据定量病理学测量 PCa 生长速率与代谢组学特征、精胺和柠檬酸盐浓度的相关性，以及针对分离的不同病理成分的精胺合成/降解途径中的酶和锌摄取蛋白 hZIP1 的 mRNA 表达水平的相关性来自临床证实的良性前列腺增生（BPH）、前列腺增生（PAH）、前列腺上皮内肿瘤（PIN）和不同级别患者的LCM前列腺腺癌 (PCa)，所有这些都具有根据一段时间内的多个 PSA 结果计算得出的可靠 PSA 速度 (Vpsa)。我们将回顾性地测量前列腺切除术后有或没有癌症生化复发（BCR）的年龄、格里森评分（GS）、病理分期和辅助治疗匹配的 PCa 患者的 PCa 侵袭性与这些测量的生物学参数的相关性。研究的成功将使我们能够建立前列腺癌的生化诊断系统，将当前基于形态学的病理学扩展到包括肿瘤代谢和分子生物学的信息。这些结果将帮助临床医生评估特定肿瘤的生物活性，确定患者预后，并为个体患者选择最合适的治疗方法，有助于加深对人类恶性肿瘤的认识，并为癌症预防、诊断和治疗的可能新方向提供新见解。