title: Detection of KRAS oncogene in peripheral blood as a predictor of the response to cetuximab plus chemotherapy in patients with metastatic colorectal cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors: Graduate Institute of Medicine, College of Medicine, College of Medicine, Taiwan.
authors: Li-Chen
authors: LC
authors: Yen
authors: Yung-Sung
authors: YS
authors: Yeh
authors: Chao-Wen
authors: CW
authors: Chen
authors: Hwei-Ming
authors: HM
authors: Wang
authors: Hsiang-Lin
authors: HL
authors: Tsai
authors: Chien-Yu
authors: CY
authors: Lu
authors: Yu-Tang
authors: YT
authors: Chang
authors: Koung-Shing
authors: KS
authors: Chu
authors: Shiu-Ru
authors: SR
authors: Lin
authors: Jaw-Yuan
authors: JY
authors: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002277:Carcinoma / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D016896:Treatment Outcome; D018631:ras Proteins / Q000032:analysis / Q000097:blood* / Q000235:genetics / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin