Detection of activated KRAS from cancer patient peripheral blood using a weighted enzymatic chip array
| Autor: | Jia-Yuan Chang, Shiu-Ru Lin, Chao-Peng Hsiao, Li-Chen Yen, Jaw-Yuan Wang, Ming-Yii Huang, Jian-Jhang Huang, Hsueh-Chiao Liu |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Oncology
medicine.medical_specialty Somatic cell Colorectal cancer Peripheral blood medicine.disease_cause Polymerase Chain Reaction General Biochemistry Genetics and Molecular Biology Neoplasms Internal medicine medicine Humans Lung cancer neoplasms DNA Primers Medicine(all) chemistry.chemical_classification Base Sequence Oncogene Biochemistry Genetics and Molecular Biology(all) business.industry Research Cancer General Medicine medicine.disease digestive system diseases respiratory tract diseases Genes ras Enzyme chemistry KRAS Activating KRAS Detection Chip Weighted enzymatic chip array (WEnCA) business |
| Zdroj: | Journal of Translational Medicine |
| ISSN: | 1479-5876 |
| DOI: | 10.1186/1479-5876-12-147 |
| Popis: | Background The KRAS oncogene was one of the earliest discoveries of genetic alterations in colorectal and lung cancers. Moreover, KRAS somatic mutations might be used for predicting the efficiency of anti-EGFR therapeutic drugs. The purpose of this research was to improve Activating KRAS Detection Chip by using a weighted enzymatic chip array (WEnCA) platform to detect activated KRAS mutations status in the peripheral blood of non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC) patients in Taiwan. Methods Our laboratory developed an Activating KRAS Detection Chip and a WEnCA technique that can detect activated KRAS mutation status by screening circulating cancer cells in the surrounding bloodstream. We collected 390 peripheral blood samples of NSCLC patients (n = 210) and CRC patients (n = 180) to evaluate clinical KRAS activation using this gene array diagnosis apparatus, an Activating KRAS Detection Chip and a WEnCA technique. Subsequently, we prospectively enrolled 88 stage III CRC patients who received adjuvant FOLFOX-4 chemotherapy with or without cetuximab. We compared the chip results of preoperative blood specimens and their relationship with disease control status in these patients. Results After statistical analysis, the sensitivity of WEnCA was found to be 93%, and the specificity was found to be 94%. Relapse status and chip results among the stage III CRC patients receiving FOLFOX-4 plus cetuximab (n = 59) and those receiving FOLFOX-4 alone (n = 29) were compared. Among the 51 stage III CRC patients with chip negative results who were treated with FOLFOX-4 plus cetuximab chemotherapy, the relapse rate was 33.3%; otherwise, the relapse rate was 48.5% among the 23 out of 88 patients with chip negative results who received FOLFOX-4 alone. Negative chip results were significantly associated to better treatment outcomes in the FOLFOX-4 plus cetuximab group (P = 0.047). Conclusions The results demonstrated that the WEnCA technique is a sensitive and convenient technique that produces easy-to-interpret results for detecting activated KRAS from the peripheral blood of cancer patients. We suggest that the WEnCA technique is also a potential tool for predicting responses in CRC patients following FOLFOX-4 plus cetuximab chemotherapy. |
| Databáze: | OpenAIRE |
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