The prognostic significance of KRAS and BRAF mutation status in Korean colorectal cancer patients

被引:35
作者
Won, Daeyoun David [1 ]
Lee, Jae Im [2 ]
Lee, In Kyu [1 ]
Oh, Seong-Taek [2 ]
Jung, Eun Sun [3 ]
Lee, Sung Hak [3 ]
机构
[1] Catholic Univ Korea, Seoul St Marys Hosp, Coll Med, Dept Surg, Seoul, South Korea
[2] Catholic Univ Korea, Uijeongbu St Marys Hosp, Coll Med, Dept Surg, Seoul, South Korea
[3] Catholic Univ Korea, Seoul St Marys Hosp, Coll Med, Dept Hosp Pathol, 222 Banpo Daero, Seoul 06591, South Korea
关键词
BRAF mutation; KRAS mutation; MSI; Colorectal cancer; DNA MISMATCH REPAIR; III COLON-CANCER; STAGE-III; MICROSATELLITE INSTABILITY; V600E MUTATION; POOR SURVIVAL; IMPACT; METASTASECTOMY; CHEMOTHERAPY; CARCINOMAS;
D O I
10.1186/s12885-017-3381-7
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: BRAF and KRAS mutations are well-established biomarkers in anti-EGFR therapy. However, the prognostic significance of these mutations is still being examined. We determined the prognostic value of BRAF and KRAS mutations in Korean colorectal cancer (CRC) patients. Methods: From July 2010 to September 2013, 1096 patients who underwent surgery for CRC at Seoul St. Mary's Hospital were included in the analysis. Resected specimens were examined for BRAF, KRAS, and microsatellite instability (MSI) status. All data were reviewed retrospectively. Results: Among 1096 patients, 401 (36.7%) had KRAS mutations and 44 (4.0%) had BRAF mutations. Of 83 patients, 77 (92.8%) had microsatellite stable (MSS) or MSI low (MSI-L) status while 6 (7.2%) patients had MSI high (MSI-H) status. Patients with BRAF mutation demonstrated a worse disease-free survival (DFS, HR 1.990, CI 1.080-3.660, P = 0. 02) and overall survival (OS, HR 3.470, CI 1.900-6.330, P < 0.0001). Regarding KRAS status, no significant difference was noted in DFS (P = 0.0548) or OS (P = 0.107). Comparing the MSS/MSI-L and MSI-H groups there were no significant differences in either DFS (P = 0.294) or OS (P = 0.557). Conclusions: BRAF mutation, rather than KRAS, was a significant prognostic factor in Korean CRC patients at both early and advanced stages. The subgroup analysis for MSI did not show significant differences in clinical outcome. BRAF should be included in future larger prospective biomarker studies on CRC.
引用
收藏
页数:12
相关论文
共 55 条
[1]   Cetuximab therapy in first-line metastatic colorectal cancer and intermittent palliative chemotherapy: review of the COIN trial [J].
Adams, Richard ;
Meade, Angela ;
Wasan, Harpreet ;
Griffiths, Gareth ;
Maughan, Tim .
EXPERT REVIEW OF ANTICANCER THERAPY, 2008, 8 (08) :1237-1245
[2]   The BRAF mutation is associated with the prognosis in colorectal cancer [J].
Ahn, Tae Sung ;
Jeong, Dongjun ;
Son, Myoung Won ;
Jung, Haeil ;
Park, Soyoung ;
Kim, Hyungjoo ;
Bae, Sang Byung ;
Kim, Han Jo ;
Jeon, Young-Woo ;
Lee, Moon Soo ;
Baek, Moo-Jun .
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2014, 140 (11) :1863-1871
[3]   Kirsten ras mutations in patients with colorectal cancer: the multicenter "RASCAL" study [J].
Andreyev, HJN ;
Norman, AR ;
Cunningham, D ;
Oates, JR ;
Clarke, PA .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1998, 90 (09) :675-684
[4]   Prognostic and Predictive Roles of KRAS Mutation in Colorectal Cancer [J].
Arrington, Amanda K. ;
Heinrich, Eileen L. ;
Lee, Wendy ;
Duldulao, Marjun ;
Patel, Supriya ;
Sanchez, Julian ;
Garcia-Aguilar, Julio ;
Kim, Joseph .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2012, 13 (10) :12153-12168
[5]  
Boland CR, 1998, CANCER RES, V58, P5248
[6]  
*CANC GEN ATL NETW, 2012, NATURE, V487, P330, DOI [10.1038/nature11252, DOI 10.1038/NATURE11252]
[7]   BRAFV600E Mutation and Its Association with Clinicopathological Features of Colorectal Cancer: A Systematic Review and Meta-Analysis [J].
Chen, Dong ;
Huang, Jun-Fu ;
Liu, Kai ;
Zhang, Li-Qun ;
Yang, Zhao ;
Chuai, Zheng-Ran ;
Wang, Yun-Xia ;
Shi, Da-Chuan ;
Huang, Qing ;
Fu, Wei-Ling .
PLOS ONE, 2014, 9 (03)
[8]  
Chen JQ, 2014, BMC CANCER, V14, DOI [10.1186/1471-2407-14-15, 10.1186/1471-2407-14-802]
[9]   Mutations of the BRAF gene in human cancer [J].
Davies, H ;
Bignell, GR ;
Cox, C ;
Stephens, P ;
Edkins, S ;
Clegg, S ;
Teague, J ;
Woffendin, H ;
Garnett, MJ ;
Bottomley, W ;
Davis, N ;
Dicks, N ;
Ewing, R ;
Floyd, Y ;
Gray, K ;
Hall, S ;
Hawes, R ;
Hughes, J ;
Kosmidou, V ;
Menzies, A ;
Mould, C ;
Parker, A ;
Stevens, C ;
Watt, S ;
Hooper, S ;
Wilson, R ;
Jayatilake, H ;
Gusterson, BA ;
Cooper, C ;
Shipley, J ;
Hargrave, D ;
Pritchard-Jones, K ;
Maitland, N ;
Chenevix-Trench, G ;
Riggins, GJ ;
Bigner, DD ;
Palmieri, G ;
Cossu, A ;
Flanagan, A ;
Nicholson, A ;
Ho, JWC ;
Leung, SY ;
Yuen, ST ;
Weber, BL ;
Siegler, HF ;
Darrow, TL ;
Paterson, H ;
Marais, R ;
Marshall, CJ ;
Wooster, R .
NATURE, 2002, 417 (6892) :949-954
[10]  
de Cuba EM, 2015, INT J CANC BOSCH LJ