Surrogate Biomarkers of Micrometastatic Gastric Cancer

微转移性胃癌的替代生物标志物

• 批准号: 6804475
• 负责人: ADAM J SMOLKA
• 金额: $ 6.39万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6804475
• 关键词: adenocarcinoma; bioassay; biomarker; biotechnology; clinical research; diagnosis design /evaluation; diagnosis quality /standard; early diagnosis; fine needle aspiration; gel electrophoresis; gene expression; human subject; lymph nodes; metastasis; molecular oncology; molecular pathology; nucleic acid amplification techniques; nucleic acid quantitation /detection; nucleic acid sequence; polymerase chain reaction; spectrometry; stomach neoplasms

DESCRIPTION (provided by applicant): The long term goal of this study is development of surrogate molecular markers for early detection of micrometastatic stomach cancer. Gastric adenocarcinoma is the second leading cause of cancer-related death in the world. With a U.S. prevalence rate of 5-7 cases per 100,000 population and 20,000 new cases per year, gastric cancer nonetheless accounts for 3% of all U.S. cancer deaths. Gastric neoplasms are predominantly (95%) adenocarcinomas which are rarely diagnosed in their early stages. At diagnosis, 25% of patients have disease confined to the stomach, 50% show locoregional lymph node metastases and extragastric spread, and 25% have distant metastases. Those patients presenting with cancer confined to the stomach are candidates for curative gastric resection. Unfortunately, about 70% of these patients die from disease relapse within 5 years of surgery. Early detection of gastric micrometastases is thus a major clinical challenge. The hypothesis driving the proposed study is that gastric epithelial cell-specific genes expressed in ectopic gastric tumor cells in lymph nodes are molecular markers for early detection of metastatic gastric cancers. Our preliminary data indicate that quantitative real-time RT-PCR readily detects expression of several mRNA transcripts in human gastric biopsies and in human gastric adenocarcinoma cells. Based on these and related RT-PCR data measuring expression of lung cancer-associated mRNAs in mediastinal lymph nodes, we propose two specific aims: 1) To identify a panel of RT-PCR primer pairs for quantitative detection of genes that may be over-expressed in malignant lymph nodes of gastric cancer patients, and 2) To establish criteria for interpretation of marker gene RT-PCR data by screening lymph node aspirates from gastric cancer patients. We anticipate that the proposed study will establish criteria for interpretation of RT-PCR data from lymph node cells acquired by endoscopic ultrasonographic-fine needle aspiration, and will serve as the basis for prospective evaluation of quantitative real-time RT-PCR and its correlation with clinical outcome in a more comprehensive cohort of patients. The successful development and validation of a lymph node RT-PCR-based assay for micrometastatic stomach cancer is likely to have a significant clinical impact.

描述（由申请人提供）： 这项研究的长期目标是替代分子标记物的发展，用于早期检测微转移性胃癌。胃腺癌是世界上与癌症相关死亡的第二大原因。胃癌的美国患病率为每100,000人口为5-7例，每年有20,000例新病例，占美国癌症死亡人数的3％。胃肿瘤主要是（95％）腺癌，在早期阶段很少被诊断出来。在诊断时，有25％的患者局限于胃，有50％的患者显示局部淋巴结转移和胃外扩散，而25％的转移有较远的转移。那些局限于胃癌的患者是治愈胃切除术的候选者。不幸的是，这些患者中约有70％在手术后的5年内死于疾病复发。因此，早期检测胃微发生是一个主要的临床挑战。推动拟议研究的假设是，在淋巴结中异位胃肿瘤细胞中表达的胃上皮细胞特异性基因是用于早期检测转移性胃癌的分子标记。我们的初步数据表明，定量实时RT-PCR容易检测到人类胃活检和人胃腺癌细胞中几个mRNA转录本的表达。 Based on these and related RT-PCR data measuring expression of lung cancer-associated mRNAs in mediastinal lymph nodes, we propose two specific aims: 1) To identify a panel of RT-PCR primer pairs for quantitative detection of genes that may be over-expressed in malignant lymph nodes of gastric cancer patients, and 2) To establish criteria for interpretation of marker gene RT-PCR data by screening淋巴结从胃癌患者中抽出。我们预计，拟议的研究将建立通过内窥镜超声检查通过淋巴结细胞解释RT-PCR数据的标准，并将作为预期评估定量实时RT-PCR及其与更全面的患者群体中临床结果相关的基础。基于淋巴结RT-PCR对微转移胃癌的成功开发和验证可能会产生重大的临床影响。