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

• 批准号: 10461807
• 负责人: Vinata B Lokeshwar
• 金额: $ 44.52万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 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/10461807
• 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

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：目前临床多采用有创诊断检查，术后复发频繁