Development of Innovative Automatic KRAS Mutation Detecting System

• Main Authors: Ming-Je Yang, 楊明哲
• Other Authors: Jaw-Yuan Wang
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/67517440745259257191

博士 === 高雄醫學大學 === 醫學研究所 === 98 === KRAS is an important oncogene which participates in the mitogen-activated protein kinase (MAPK) pathway. The activation of MAPK pathway involves in various cellular functions, including cell proliferation, differentiation and migration. Another important gene, epidermal growth factor receptor (EGFR), is also well known to play a crucial role in tumorigenesis. EGFR and KRAS mutations are found in many types of malignancies. However, mutations in these two genes are mutually exclusive, and they exhibit many contrasting characteristics like clinical background, pathological features of patients harboring each mutation, and prognostic or predictive implications. Accordingly, first we analyzed KRAS and EGFR variants in non-small cell lung cancer and compare the results with literature review. Nowadays, the identification of metastatic colorectal cancer (mCRC) patients who harbor KRAS mutants is an important work prior to addition of anti-EGFR monoclonal antibodies to standard chemotherapy. Previously we have successively established colorimetric membrane array (CLMA) for detecting KRAS mutation from circular tumor cells of various cancer patients, this technique might be applied in clinical evaluation of anti-EGFR monoclonal antibodies to predict the therapeutic response of metastatic cancer patients, especially in non-small cell lung cancer (NSCLC) and mCRC. In order to improve the detecting efficiency, we developed a novel platform-weighted chemiluminescent membrane array (WCHMA). The current results demonstrate that the accuracy of WCHMA (NSCLC: 93.8%, mCRC: 93.5%) is higher than that of CLMA (NSCLC: 91.9%, mCRC: 90.8%). Furthermore, medical automation technology is the futured trend for which it can reduce labor, operation errors, and time-consumimg. Finally, we intend to establish an automatic gene chip detecting system for medical diagnosis. We have confidence in that WCHMA and automatic gene chip detecting system have great potential and advantage for basic research and clinical implication in the future.