http://scholars.ntou.edu.tw/handle/123456789/19270
標題: | Molecular Detection of APC, K-ras, and p53 Mutations in the Serum of Colorectal Cancer Patients as Circulating Biomarkers | 作者: | Jaw-Yuan Wang Jan-Sing Hsieh Mei-Yin Chang Tsung-Jen Huang Fang-Ming Chen Tian-Lu Cheng Ketil Alexandersen Yu-Sheng Huang Wen-Shyong Tzou Shiu-Ru Lin |
公開日期: | 七月-2004 | 出版社: | World Journal of Surgery | 卷: | 28 | 期: | 7 | 起(迄)頁: | 721-726 | 來源出版物: | Original Scientific Reports | 摘要: | Early detection of tumor DNA in serum/plasma prior to the development of recurrence or metastases could help improve the outcome of patients with colorectal cancer (CRC) after tumor resection. Recent advances in the detection of tumor DNA in the serum/plasma has opened up numerous new areas for investigation and new possibilities for molecular diagnosis. APC and K-ras mutations are considered to be early-stage developments of CRCs, whereas p53 mutations are thought to be relatively late events in the tumorigenesis of CRCs. The aim of this study was to search for the presence of genetic mutations in the DNA extracted from the serum of CRC patients and healthy subjects. We simultaneously evaluate the significance of APC, K-ras, and p53 gene mutations in cancer tissues and their paired serum samples of 104 CRC patients by polymerase chain reaction-single strand conformation polymorphism analysis (PCR-SSCP) followed by direct sequencing. Additionally, analysis was carried out to detect the serum carcinoembryonic antigen (CEA) levels in CRC patients. Overall, we found at least one of the gene mutations in tumor tissues from 75% (78/104) of the CRC patients. Comparison of the three molecular markers showed that the detection rates in the serum were 30.4%, 34.0%, and 34.2% for APC, K-ras, and p53 genes, respectively. Of these patients, 46.2% (36/78) were identified as having positive serum results, whereas all healthy controls remained negative. The overall positive tumor DNA detection rates in the serum were 0% (0/7) for Dukes’ A classification, 22.4% (11/49) for Dukes’ B, 48.7% (19/39) for Dukes’ C, and 66.7% (6/9) for Dukes’ D. The detection rate increased as the tumor stage progressed (p = 0.012). Concurrently, a significant difference was observed between lymph node metastases and positive serum tumor DNA detection (p < 0.001). A significantly higher postoperative metastasis/recurrence rate in patients harboring gene mutations with serum tumor DNA than those without serum tumor DNA was also demonstrated (p < 0.001). However, no significant correlation between the postoperative metastasis/recurrence and serum CEA levels was observed (p = 0.247). These data suggest that the identification of circulating tumor DNA using the molecular detection of APC, K-ras, and p53 gene mutations is a potential tool for early detection of postoperative recurrence/metastases. Moreover, these genes may be potential molecular markers of poor clinical outcome in CRC patients. |
URI: | http://scholars.ntou.edu.tw/handle/123456789/19270 | DOI: | 10.1007/s00268-004-7366-8 |
顯示於: | 生命科學暨生物科技學系 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。