公开(公告)号：US20110306055A1

公开(公告)日：2011-12-15

申请号：US12935201

申请日：2010-02-24

申请人： Jean-Francois Haince ,  Guillaume Beaudry ,  Genevieve Garon ,  Michel Houde ,  Timothy J. Holzer ,  Martin Beaulieu ,  Nicolas Bertrand

发明人： Jean-Francois Haince ,  Guillaume Beaudry ,  Genevieve Garon ,  Michel Houde ,  Timothy J. Holzer ,  Martin Beaulieu ,  Nicolas Bertrand

IPC分类号： C12Q1/68

CPC分类号： G01N33/57419 ,  C12Q1/34 ,  C12Q1/527 ,  G01N33/573 ,  G01N2800/52

摘要： The present invention provides a novel method for diagnosing, monitoring, prognosing and staging Lymph Node (LN) status in colorectal cancer (CRC) that is more sensitive and accurate than conventional detection technologies such as histopathology. The Guanylyl Cyclase C (GCC) gene is specifically expressed in apical epithelial cells of the GI tract from the duodenum to the rectum and the detection of GCC mRNA in LNs is indicative of the presence of metastases. Quantitative RT-PCR (RT-qPCR) detection of GCC mRNA to identify the presence of colorectal cancer (CRC) cells in LNs has the potential to aid in CRC staging. When used in combination with glucuronidase B (GUSB), accurate quantification of GCC can be achieved with less than a 2-fold variation between intact and highly degraded RNA specimens. The invention also relates to a newly designed GCC/GUSB assay that uses relative quantification having improved prognostic value for time to recurrence and relapse-free survival in Stage I or II colon cancer patients. The GCC/GUSB assay also improves the statistical power of prognosis stratification for relative risk of recurrence and relapse-free survival.

摘要翻译： 本发明提供了一种用于诊断，监测，预后和分期结直肠癌（CRC）中的淋巴结（LN）状态的新方法，其比常规检测技术如组织病理学更灵敏和准确。 Guanylyl Cyclase C（GCC）基因在十二指肠至直肠胃肠道的顶端上皮细胞中特异性表达，LN检测GCC mRNA表示存在转移灶。 定量RT-PCR（RT-qPCR）检测GCC mRNA以鉴定LN中结肠直肠癌（CRC）细胞的存在有助于CRC分期。 当与葡糖醛酸糖苷酶B（GUSB）组合使用时，可以在完整和高度降解的RNA标本之间以小于2倍的变化实现GCC的准确定量。 本发明还涉及一种新设计的GCC / GUSB测定法，其使用相对定量，其具有改善I期或II期结肠癌患者的复发和无复发存活时间的预后价值。 GCC / GUSB测定还提高了复发和无复发生存相对风险的预后分层的统计学功能。