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开发用于早期检测微转移性胃癌的替代分子标记。胃腺癌是世界上癌症相关死亡的第二大原因。尽管美国的患病率为每 100,000 人 5-7 例，每年新增 20,000 例胃癌，但胃癌仍占美国癌症死亡总数的 3%。胃肿瘤主要（95%）是腺癌，很少在早期诊断出来。诊断时，25%的患者疾病局限于胃部，50%显示局部淋巴结转移和胃外扩散，25%有远处转移。那些患有局限于胃的癌症的患者是治愈性胃切除术的候选者。不幸的是，大约 70% 的患者在手术后 5 年内死于疾病复发。因此，胃微转移的早期检测是一项重大的临床挑战。推动这项研究的假设是，淋巴结异位胃肿瘤细胞表达的胃上皮细胞特异性基因是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 可以轻松检测人胃活检和人胃腺癌细胞中几种 mRNA 转录本的表达。基于这些以及测量纵隔淋巴结中肺癌相关mRNA表达的相关RT-PCR数据，我们提出了两个具体目标：1）确定一组RT-PCR引物对，用于定量检测胃癌患者恶性淋巴结中可能过度表达的基因，2）通过筛选建立标记基因RT-PCR数据的解释标准 胃癌患者的淋巴结抽吸。我们预计，拟议的研究将为通过内镜超声细针抽吸获得的淋巴结细胞的 RT-PCR 数据的解释建立标准，并将作为定量实时 RT-PCR 的前瞻性评估及其与更全面的患者队列中临床结果的相关性的基础。基于淋巴结 RT-PCR 的微转移性胃癌检测方法的成功开发和验证可能会产生重大的临床影响。