Prosaposin, a novel tumor marker for prostate cancer

Prosaposin，前列腺癌的新型肿瘤标志物

• 批准号: 7230060
• 负责人: SHAHRIAR KOOCHEKPOUR
• 金额: $ 13.1万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7230060
• 关键词: Affect; Age; Androgens; Apoptotic; Atrophic; Behavior; Biological; Biological Assay; Biological Markers; Biopsy Specimen; Cancer Patient; Cell Proliferation; Cell Survival; Characteristics; Clinical; Clinical Trials; Data; Development; Diagnosis; Differentiation Antigens; Disease; Disease Progression; Early Diagnosis; Endopeptidases; Epithelial Cells; Freezing; Future; Genes; Gleason Grade for Prostate Cancer; Goals; Growth; Growth Factor; Hormones; Indolent; Investigation; Laboratories; Lead; Malignant neoplasm of prostate; Measures; Messenger RNA; Metastatic Prostate Cancer; Methodology; Molecular; PC3 cell line; PSA level; Paraffin Embedding; Patients; Pattern; Peptide Hydrolases; Polymerase Chain Reaction; Population; Predictive Factor; Proliferating; Prostate; Prostatic; Prostatic Epithelium; Proteins; Punch Biopsy; Race; Radical Prostatectomy; Recurrence; Refractory; Research Personnel; Risk Factors; Role; Screening for Prostate Cancer; Secretory Cell; Sensitivity and Specificity; Serum; Severities; Specimen; Staging; Stratification; TNM; Testing; Time; Tissue Microarray; Tissue Sample; Tissue Stains; Tissues; Transgenic Mice; Treatment outcome; Tumor Markers; Tumor Volume; Undifferentiated; Validity and Reliability; Xenograft procedure; base; cancer cell; carcinogenesis; clinically significant; design; disease characteristic; follow-up; hormone refractory prostate cancer; improved; laser capture microdissection; lymph nodes; male; malignant state; migration; neoplastic cell; novel; prognostic; programs; prospective; protein expression; response; serum PSA; tumor

DESCRIPTION (provided by applicant): Identification of tumor markers that are expressed at high amounts only in malignant state and correlate with disease stage and progression are needed to improve the diagnosis and treatment of prostate cancer (PCa). We have cloned prosaposin from the poorly differentiated androgen-independent (Al) PCa cell line, PC-3. Our results to date show: 1) prosaposin expression is higher in metastatic Al than in androgen-dependent (AD) PCa cells, 2) serum levels of prosaposin is higher in hormone-refractory PCa patients than in the normal male population, 3) prosaposin gene is amplified in PCa cells and punch biopsy specimens of prostate cancer xenografts and metastatic lymph nodes, and 4) prosaposin stimulates growth, migration, and invasion and acts as a cell survival and anti-apoptotic factor in both AD and Al PCa cells. These results lead us to propose the hypothesis that prosaposin contributes to prostate carcinogenesis and has the characteristics of a PCa tumor marker. Thus, the goal of this project is to establish the usefulness of this molecule as a tumor marker for prostate cancer. The Specific Aims of this R21 project are: 1. To assess, in proliferating tumor cells from prostate cancer tissues, the relationship between prosaposin expression and patients' Gleason's score and serum-PSA level. We will use immunohistochemical staining and tissue microarray to measure prosaposin expression level in proliferating (Ki-67 positive) tumor cells and its relationship with the two most important current predictive factors, Gleason's score (GS) and PSA. 2. To define the clinical significance of prosaposin expression as a marker of differentiation or disease progression in prostate cancer. Using sensitive quantitative laser capture microdissection, Real-Time PCR, and DELFIA-prosaposin immunoquantification assays, we will: a) in frozen tissue sections of radical prostatectomy specimens, assess the correlation between prosaposin (mRNA and protein) expression and dominant Gleason's pattern (as a measure of glandular differentiation), and b) in sera from patients, evaluate the relationship between prosaposin and metastatic versus non-metastatic PCa, hormone-sensitive versus hormone-refractory, and other prognostic or risk factors (e.g., PSA, GS, age, race) Significance. The results of this exploratory (R21) project will provide the basis for design of future large- scale prospective clinical investigation that will test the validity, reliability, and predictability of prosaposin as a tumor marker in relationship to PCa severity, progression, response to treatment, and outcomes.

描述（由申请人提供）：需要鉴定仅在恶性状态下大量表达且与疾病阶段和进展相关的肿瘤标志物，以改善前列腺癌（PCa）的诊断和治疗。我们从低分化的雄激素非依赖性（A1）PCa细胞系PC-3中克隆了prosaposin。迄今为止，我们的结果显示：1) 转移性 A1 中的前列腺素表达高于雄激素依赖性 (AD) PCa 细胞，2) 激素难治性前列腺癌患者中前列腺素的血清水平高于正常男性人群，3) 前列腺癌异种移植物和转移淋巴结的 PCa 细胞和穿刺活检标本中前列腺素基因被扩增，4) 前列腺素 刺激生长、迁移和侵袭，并在 AD 和 Al PCa 细胞中充当细胞存活和抗凋亡因子。这些结果使我们提出这样的假设：prosaposin 有助于前列腺癌发生并具有 PCa 肿瘤标志物的特征。因此，该项目的目标是确定该分子作为前列腺癌肿瘤标志物的有用性。该R21项目的具体目标是： 1. 评估前列腺癌组织中增殖的肿瘤细胞中prosaposin表达与患者Gleason评分和血清PSA水平之间的关系。我们将使用免疫组织化学染色和组织微阵列来测量增殖（Ki-67 阳性）肿瘤细胞中 prosaposin 的表达水平及其与当前两个最重要的预测因素 Gleason 评分 (GS) 和 PSA 的关系。 2. 确定前列腺癌中前列腺癌分化或疾病进展标志物的前列腺素表达的临床意义。使用敏感定量激光捕获显微切割、实时 PCR 和 DELFIA-prosaposin 免疫定量测定，我们将：a) 在根治性前列腺切除术标本的冷冻组织切片中，评估 prosaposin（mRNA 和蛋白质）表达与显性格里森模式（作为腺体分化的测量）之间的相关性，b) 在患者血清中，评估之间的关系 前列腺素与转移性与非转移性 PCa、激素敏感与激素难治性以及其他预后或风险因素（例如 PSA、GS、年龄、种族）的意义。该探索性 (R21) 项目的结果将为未来大规模前瞻性临床研究的设计提供基础，该研究将测试 proaposin 作为肿瘤标志物与 PCa 严重程度、进展、治疗反应和结果相关的有效性、可靠性和可预测性。