Surrogate Biomarkers of Micrometastatic Gastric Cancer

描述（由申请人提供）： 本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物。胃腺癌是世界上第二大癌症相关死亡原因。美国的患病率为每10万人5-7例，每年新发病例2万例，但胃癌仍占美国所有癌症死亡的3%。胃肿瘤主要是腺癌（95%），很少在早期诊断。在诊断时，25%的患者疾病局限于胃，50%显示局部淋巴结转移和胃外扩散，25%有远处转移。那些表现为局限于胃的癌症的患者是根治性胃切除术的候选者。不幸的是，这些患者中约有70%在手术后5年内死于疾病复发。因此，早期检测胃微转移是一个重大的临床挑战。该研究的假设是，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转移性胃癌早期检测的分子标志物。我们的初步数据表明，定量实时RT-PCR很容易检测几个mRNA转录在人胃活检和人胃腺癌细胞的表达。基于这些和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表达的基因，（2）通过对胃癌患者淋巴结穿刺物的筛选，建立标志基因RT-PCR数据的解释标准。我们预计，拟议的研究将建立标准的解释RT-PCR数据从淋巴结细胞获得的内镜超声细针穿刺，并将作为基础的前瞻性评价定量实时RT-PCR及其相关性与临床结果在一个更全面的队列的患者。淋巴结RT-PCR为基础的检测微转移胃癌的成功开发和验证可能会有显着的临床影响。

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.