Novel Biomarkers for the Clinical Management of Bladder Cancer

用于膀胱癌临床管理的新型生物标志物

基本信息

批准号：
10198863
负责人：
Vinata B Lokeshwar
金额：
$ 1.57万
依托单位：
AUGUSTA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-13 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10198863
关键词：
Adjuvant Benign Biological Markers Bladder Bladder Neoplasm Blinded Cancer Patient Chemoresistance Chemotherapy-Oncologic Procedure Chondroitin Sulfate Proteoglycan Chondroitinases Cisplatin Clinic Clinical Clinical Management Cystectomy Cystoscopy Cytology Diagnosis Diagnostic Disease Disease Progression Early Diagnosis Early Intervention Enzyme-Linked Immunosorbent Assay Enzymes Evaluation Excision FDA approved Family Future Genes Genitourinary system Glycosaminoglycans Goals Growth Hematuria Human Immunohistochemistry Infection Invaded Laboratories Longitudinal prospective study Malignant - descriptor Malignant Neoplasms Malignant neoplasm of urinary bladder Measures Messenger RNA Microscopic Monitor Morbidity - disease rate Muscle Development Names Neoplasm Metastasis Non-Invasive Cancer Detection Operative Surgical Procedures Outcome Pain Painless Patients Persons Pilot Projects Positive Test Result Procedures Prospective Studies RNA Splicing Recurrence Research Design Resistance Retrospective Studies Risk Risk Factors Specificity Specimen Spottings Symptoms Test Result Testing Tissues Urine Urography Urothelial Cell Validation Variant accurate diagnosis base cancer diagnosis cancer recurrence chemotherapy clinical practice cost design detrusor muscle diagnosis evaluation efficacy testing follow-up gemcitabine improved individualized medicine member mortality muscle invasive bladder cancer noninvasive diagnosis novel novel marker predict clinical outcome predicting response prognostic public health relevance rate of change response tissue biomarkers treatment response tumor tumor growth urologic validation studies

项目摘要

ABSTRACT: The current clinical practice of invasive diagnostic workup, frequent recurrence following bladder tumor resection, and high propensity of muscle invasive bladder cancer (MIBCa) for metastasis, contribute to the significant morbidity and mortality associated with bladder cancer (BCa); one of the costliest cancer to manage clinically. Painless hematuria is the common presenting symptom among BCa patients. However, only 15-25% of patients with visible hematuria and about 10% of the patients with microscopic hematuria actually have BCa. Patients presenting with hematuria undergo urological workup that involves cystoscopy and CT- urography. Cystoscopy is invasive and uncomfortable and both procedures associate with considerable risk for morbidity and are costly. Frequent BCa recurrence requires surveillance by cystoscopy every 3 to 6 months. Non-invasive biomarkers, including urine cytology, can reduce the invasive and costly workup among patients with hematuria or for those under surveillance for monitoring BCa recurrence. However, existing biomarkers are not used in clinic due to their sub-optimal efficacy and/or high false-positive rate. Further, biomarkers are not used for predicting clinical outcome in terms of metastasis or treatment response after a bladder removal surgery. In pilot studies, two new non-invasive tests based on a novel member of a glycosaminoglycan family, showed high accuracy to detect BCa, for non-invasively evaluating its grade and for early detection of BCa recurrence. Biomarker levels in BCa tissues correlated with clinical outcome. This project is designed to evaluate a hypothesis that this two urine tests can accurately diagnose BCa and non-invasively evaluate its grade among patients needing urological workup for hematuria, or to monitor BCa recurrence. Furthermore the tissue-based biomarkers accurately predict clinical outcome. The efficacy of both urine tests will be evaluated for BCa diagnosis and for evaluation of its grade among patients undergoing urological workup for hematuria (Aim 1). Efficacy of these urine tests will be compared to cystoscopy findings in patients under surveillance for monitoring BCa recurrence. The tests’ findings will also be evaluated for predicting future recurrence (Aim 2). The biomarkers’ expression in BCa tissues will be examined for predicting the development of MIBCa, metastasis and overall clinical outcome (Aim3). Impact: The study may result in two validated urine tests for non-invasively and accurately detecting BCa with grade evaluation as an added benefit. This could substantially reduce the number of patients undergoing urological workup for hematuria or surveillance cystoscopies for monitoring BCa recurrence. Tissue biomarkers, if found to be accurate prognosticators, could reduce unnecessary invasive bladder re-resections for MIBCa, and aid in early intervention and individualized treatment for patients with advanced BCa. Overall, if efficacious, these biomarkers could reduce BCa-related morbidity, and costs, while improving clinical outcome by early predictions.

摘要：当前侵入性诊断检查的临床实践，经常在膀胱后复发肿瘤切除和肌肉浸润性膀胱癌（MIBCA）的高度可靠性，有助于与膀胱癌（BCA）相关的显着发病率和死亡率；最昂贵的癌症之一临床管理。无痛性血尿是BCA患者中常见的症状。但是，只有 15-25％的可见血尿患者和大约10％的微观血尿患者有BCA。出现血尿的患者接受泌尿科检查，涉及膀胱镜检查和CT- 泌尿外科。膀胱镜检查是侵入性和不舒服的，这两个程序都与可考虑的风险有关发病率很高。频繁的BCA复发需要每3至6个月进行一次膀胱镜检查进行监视。非侵入性生物标志物（包括尿细胞学）可以减少患者的侵入性和昂贵的检查使用血液或正在监视的监测患者进行监测BCA复发。但是，现有的生物标志物是由于其亚最佳效率和/或高阳性率，因此未在诊所中使用。此外，生物标志物不是用于预测膀胱清除手术后转移或治疗反应的临床结果。在试点研究中，基于糖胺聚糖家族的新成员的两个新的非侵入性测试，表现出很高的检测BCA的精度，用于非侵入性评估其等级和早期检测到BCA 复发。 BCA组织中的生物标志物水平与临床结果相关。该项目旨在评估这两个尿液测试可以准确诊断BCA并非侵入性评估其等级的假设需要泌尿外科检查的患者或监测BCA复发的患者。此外，基于组织生物标志物可以准确预测临床结果。两种尿液测试的效率将用于BCA诊断和评估其等级接受血尿泌尿外科检查的患者（AIM 1）。将这些尿液检查的功效与监测监测BCA复发的患者的膀胱镜检查结果。测试的发现也将是评估预测未来复发（AIM 2）。将检查生物标志物在BCA组织中的表达用于预测MIBCA，转移和整体临床结果的发展（AIM3）。影响：该研究可能会导致两次经过验证的尿液测试，以便非侵入性准确检测BCA 等级评估是一个额外的好处。这可以大大减少正在接受的患者的数量血尿或监测膀胱镜检查的泌尿外科检查，用于监测BCA复发。组织生物标志物，如果发现是准确的预后剂，则可以减少对Mibca的不必要的侵入性膀胱重新分辨并为晚期BCA患者提供早期干预和个性化治疗。总的来说，即使效率这些生物标志物可以降低与BCA相关的发病率和成本，同时早期改善临床结果预测。