BACKGROUND: The discovery of practical biomarkers is important to realize personalized medicine for patients with malignant neoplasias, including colorectal cancer (CRC). PURPOSE: The aim of this study was to determine reliable prognostic biomarkers by the analysis of patients with resectable colorectal liver metastases (CRLM). METHODS: Genomic DNA was obtained from the CRLM tissues of a cohort of 126 patients with CRLM with curative hepatic resection. The KRAS/BRAF mutation spectrum and microsatellite instability (MSI) status were successfully analyzed in 100 of the 126 CRLM tissues and these findings were examined in relation to the patients' clinical outcomes. RESULTS: The cohort of 100 CRLM patients consisted of 46 with synchronous and 54 with metachronous liver metastasis. Overall survival and disease-free survival at 5 years were 57.4 and 24.9 %, respectively. MSI analysis revealed that none of the 100 CRLM specimens showed any evidence of MSI. By KRAS/BRAF mutation analysis, the analyzed CRLM patients were divided into 3 groups; KRAS-mutant (KRAS-Mt; n = 27), BRAF-mutant (BRAF-Mt; n = 3), and wild-types of both genes (Wild-type; n = 70). In the survival analysis, both KRAS-Mt and BRAF-Mt patients showed significantly poorer prognoses compared with Wild-type patients. Furthermore, although the population with the BRAF mutation was small, this mutation had a significant negative impact on disease-free survival. CONCLUSIONS: In this study, all tumors in the cohort of CRLM patients were non-MSI tumors, suggesting MSI cancer in primary CRC would rarely reveal metastatic potential. KRAS and BRAF mutations are suggested to be poor prognostic factors in CRLM. Genetic information has an essential role as a prognostic marker and could contribute to the decisions on treatment strategy for CRLM.
BACKGROUND: The discovery of practical biomarkers is important to realize personalized medicine for patients with malignant neoplasias, including colorectal cancer (CRC). PURPOSE: The aim of this study was to determine reliable prognostic biomarkers by the analysis of patients with resectable colorectal liver metastases (CRLM). METHODS: Genomic DNA was obtained from the CRLM tissues of a cohort of 126 patients with CRLM with curative hepatic resection. The KRAS/BRAF mutation spectrum and microsatellite instability (MSI) status were successfully analyzed in 100 of the 126 CRLM tissues and these findings were examined in relation to the patients' clinical outcomes. RESULTS: The cohort of 100 CRLM patients consisted of 46 with synchronous and 54 with metachronous liver metastasis. Overall survival and disease-free survival at 5 years were 57.4 and 24.9 %, respectively. MSI analysis revealed that none of the 100 CRLM specimens showed any evidence of MSI. By KRAS/BRAF mutation analysis, the analyzed CRLM patients were divided into 3 groups; KRAS-mutant (KRAS-Mt; n = 27), BRAF-mutant (BRAF-Mt; n = 3), and wild-types of both genes (Wild-type; n = 70). In the survival analysis, both KRAS-Mt and BRAF-Mt patients showed significantly poorer prognoses compared with Wild-type patients. Furthermore, although the population with the BRAF mutation was small, this mutation had a significant negative impact on disease-free survival. CONCLUSIONS: In this study, all tumors in the cohort of CRLM patients were non-MSI tumors, suggesting MSI cancer in primary CRC would rarely reveal metastatic potential. KRAS and BRAF mutations are suggested to be poor prognostic factors in CRLM. Genetic information has an essential role as a prognostic marker and could contribute to the decisions on treatment strategy for CRLM.
Authors: Yoshikuni Kawaguchi; Scott Kopetz; Timothy E Newhook; Mario De Bellis; Yun Shin Chun; Ching-Wei D Tzeng; Thomas A Aloia; Jean-Nicolas Vauthey Journal: Clin Cancer Res Date: 2019-06-20 Impact factor: 12.531
Authors: Georgios Antonios Margonis; Stefan Buettner; Nikolaos Andreatos; Yuhree Kim; Doris Wagner; Kazunari Sasaki; Andrea Beer; Christoph Schwarz; Inger Marie Løes; Maria Smolle; Carsten Kamphues; Jin He; Timothy M Pawlik; Klaus Kaczirek; George Poultsides; Per Eystein Lønning; John L Cameron; Richard A Burkhart; Armin Gerger; Federico N Aucejo; Martin E Kreis; Christopher L Wolfgang; Matthew J Weiss Journal: JAMA Surg Date: 2018-07-18 Impact factor: 14.766
Authors: Cristian D Valenzuela; Omeed Moaven; Rohin Gawdi; John A Stauffer; Nico R Del Piccolo; Tan To Cheung; Carlos U Corvera; Andrew D Wisneski; Charles Cha; Christopher W Mangieri; Nima P Zarandi; Justin Dourado; Kathleen C Perry; Gregory Russell; Perry Shen Journal: HPB (Oxford) Date: 2022-02-28 Impact factor: 3.842
Authors: M Schirripa; F Bergamo; C Cremolini; M Casagrande; S Lonardi; G Aprile; D Yang; F Marmorino; G Pasquini; E Sensi; C Lupi; G De Maglio; N Borrelli; S Pizzolitto; G Fasola; R Bertorelle; M Rugge; G Fontanini; V Zagonel; F Loupakis; A Falcone Journal: Br J Cancer Date: 2015-05-05 Impact factor: 7.640
Authors: Carrie Luu; Eileen L Heinrich; Marjun Duldulao; Amanda K Arrington; Marwan Fakih; Julio Garcia-Aguilar; Joseph Kim Journal: PLoS One Date: 2013-08-01 Impact factor: 3.240