Detection of KRAS Oncogene in Peripheral Blood as a Predictor of the Response to Cetuximab Plus Chemotherapy in Patients with Metastatic Colorectal Cancer
| Autor: | Hsiang Lin Tsai, Hwei-Ming Wang, Jaw-Yuan Wang, Shiu-Ru Lin, Chien-Yu Lu, Yung-Sung Yeh, Yu-Tang Chang, Koung-Shing Chu, Chao-Wen Chen, Li-Chen Yen |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Oncology Cancer Research Pathology Organoplatinum Compounds Colorectal cancer medicine.medical_treatment DNA Mutational Analysis Leucovorin Cetuximab medicine.disease_cause Metastasis Circulating tumor cell Antineoplastic Combined Chemotherapy Protocols Neoplasm Metastasis Aged 80 and over Antibodies Monoclonal Middle Aged Neoplastic Cells Circulating Prognosis Treatment Outcome FOLFIRI Female Fluorouracil KRAS Colorectal Neoplasms medicine.drug Adult medicine.medical_specialty Antineoplastic Agents Antibodies Monoclonal Humanized Proto-Oncogene Proteins p21(ras) Proto-Oncogene Proteins Internal medicine medicine Humans neoplasms Aged Retrospective Studies Chemotherapy business.industry Carcinoma Cancer medicine.disease digestive system diseases ras Proteins Camptothecin business |
| Zdroj: | Clinical Cancer Research. 15:4508-4513 |
| ISSN: | 1557-3265 1078-0432 |
| Popis: | Purpose: Previously we developed membrane-arrays as a promising tool to detect circulating tumor cells (CTC) with KRAS oncogene in patients with malignancies. This study was conducted to determinate the predictive values of CTCs with KARS mutation by membrane-arrays for metastatic colorectal cancer patients treated with cetuximab plus chemotherapy. Experimental Design: Seventy-six metastatic colorectal cancer patients receiving cetuximab plus FOLFIRI or FOLFOX-4 chemotherapy were enrolled. KRAS mutation status in the peripheral blood of these patients was analyzed using membrane-arrays, and KRAS mutation status in tumors was analyzed by DNA sequencing. Results: Among 76 metastatic colorectal cancer patients, KRAS mutations in tumors and in peripheral blood were identified in 33 (43.4%) and 30 (39.5%) patients, respectively. The detection sensitivity, specificity, and accuracy of membrane-arrays for CTCs with KRAS oncogene were 84.4%, 95.3%, and 90.8%, respectively, and indeed a highly significant correlation to KRAS mutations in tumors (P < 0.0001) was observed. Forty-five (59.2%) patients responded to cetuximab plus chemotherapy, and 41 and 40 were wild-type KRAS in tumors and peripheral blood, respectively (both P < 0.0001). Patients with tumors that harbor wild-type KRAS are more likely to have a better progression-free survival and overall survival when treated with cetuximab plus chemotherapy (P < 0.0001). Likewise, patients with CTCs of wild-type KRAS in peripheral blood express a better progression-free survival and overall survival when treated with cetuximab plus chemotherapy (P < 0.0001). Conclusions: These findings provide evidence that detection of KRAS mutational status in CTCs, by gene expression array, has potential for clinical application in selecting metastatic colorectal cancer patients most likely to benefit from cetuximab therapy. |
| Databáze: | OpenAIRE |
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