HCG Isoform Markers of Trophoblastic Malignancies

滋养细胞恶性肿瘤的 HCG 亚型标志物

• 批准号: 6784718
• 负责人: Steven Birken
• 金额: $ 20.44万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6784718
• 关键词: biomarker; carbohydrates; choriocarcinoma; chorionic gonadotropin; clinical research; diagnosis design /evaluation; embryo neoplasm; glycoprotein structure; glycosylation; human tissue; immunologic assay /test; neoplasm /cancer immunodiagnosis; pregnancy disorder; protein isoforms; trophoblast; women' s health

DESCRIPTION (provided by applicant): HCG is the main tumor marker for both gestational and non-gestational trophoblastic disease. After a pregnancy with partial or complete hydatidiform mole, some patients develop malignant gestational trophoblastic disease. Patients may display unexplained elevation of circulating hCG with no evidence of clinical disease and are treated solely because of their hCG marker. Other patients under treatment develop resistance to therapy or relapse as detected by the hCG marker. We propose to assess the utility of several new immunoassays for hCG isoforms, recently developed in our laboratory, as improved hCG-related tumor markers. New markers may help to identify the subpopulation of women who will require chemotherapy from those who will undergo spontaneous remission after a premalignant molar pregnancy. The new markers may also improve therapeutic care for both gestational and non-gestational trophoblastic disease patients, including testicular cancers. These markers are based on four differentiating immunoassay systems to: 1.carbohydrate-related variants of hCG. 2. "nicked" forms of hCG. 3. isoforms both "nicked" and hyperglycosylated. 4. hCG and hLH beta core fragments. Most of these hCG isoforms have been shown to be structurally altered in malignancies but no assay measurement systems existed previously to quantify these isoforms. The hCG isoforms produced by healthy individuals (from pituitary) must be clearly differentiated from those isoforms produced by malignant tissues. The detection of carbohydrate-variant hCG isoforms are based on the antibody B152 (developed to choriocarcinoma-secreted hCG isoforms) which detects a differentially O-glycosylated form of hCG produced very early in pregnancy as well as in various malignancies. HCG-secreting cancers have also been reported to produce "nicked" hCG isoforms with peptide bond cleavages within the beta subunit. These will be measured by assay system (B151) in conjunction with a rapid chromatographic procedure. Choriocarcinoma and other trophoblastic cancers produce isoforms, which are both "nicked", and hyperglycosylated. These are detected by a B151 capture B152 detection assay. Systems to specifically measure urinary hCG and urinary hLH metabolites have also been developed so that hCG-related metabolites can be distinguished from normal hLH metabolites in postmenopausal women. Structural analyses will be performed to correlate isoform structures with assay measurements.

描述（申请人提供）：HCG是妊娠和非妊娠滋养细胞疾病的主要肿瘤标志物。妊娠合并部分或完全性葡萄胎后，有些患者会发展为恶性妊娠滋养细胞疾病。患者可能会出现不明原因的循环hCG升高，没有临床疾病的证据，并仅因其hCG标志物而接受治疗。其他接受治疗的患者会对治疗产生耐药性或通过hCG标记物检测复发。我们建议评估几种新的免疫测定hCG亚型的效用，最近在我们的实验室开发的，作为改进的hCG相关的肿瘤标志物。新的标记物可能有助于鉴别需要化疗的妇女亚群和恶性前磨牙妊娠后自发缓解的妇女亚群。新的标记物还可以改善妊娠和非妊娠滋养细胞疾病患者的治疗护理，包括睾丸癌。这些标记物基于四种区分免疫测定系统：1. hCG的碳水化合物相关变体。2. hCG的"切口"形式。3. "切口的"和高糖基化的同种型。4. hCG和hLH β核心片段。这些hCG亚型中的大多数已被证明在恶性肿瘤中发生结构改变，但以前没有测定测量系统来定量这些亚型。由健康个体产生的hCG亚型（来自垂体）必须与由恶性组织产生的那些亚型明确区分。碳水化合物变体hCG同种型的检测基于抗体B152（开发用于绒毛膜癌分泌的hCG同种型），其检测在妊娠早期以及各种恶性肿瘤中产生的hCG的差异O-糖基化形式。据报道，HCG分泌型癌症也会产生β亚基内具有肽键断裂的"切口" hCG同种型。这些将通过测定系统（B151）结合快速色谱法进行测定。绒毛膜癌和其他滋养层癌产生同种型，其都是"切口的"和高糖基化的。这些通过B151捕获B152检测测定来检测。专门测量尿hCG和尿hLH代谢物的系统也已经开发出来，以便在绝经后妇女中将hCG相关代谢物与正常hLH代谢物区分开来。将进行结构分析，以将亚型结构与试验测量值相关联。