Literature DB >> 24889488

KRAS mutation is associated with worse prognosis in stage III or high-risk stage II colon cancer patients treated with adjuvant FOLFOX.

Dae-Won Lee1, Kyung Ju Kim, Sae-Won Han, Hyun Jung Lee, Ye Young Rhee, Jeong Mo Bae, Nam-Yun Cho, Kyung-Hun Lee, Tae-Yong Kim, Do-Youn Oh, Seock-Ah Im, Yung-Jue Bang, Seung-Yong Jeong, Kyu Joo Park, Jae-Gahb Park, Gyeong Hoon Kang, Tae-You Kim.   

Abstract

BACKGROUND: Although KRAS mutation has a predictive role in stage IV colorectal cancer (CRC) patients treated with anti-EGFR therapy, there have been controversies in the prognostic impact of KRAS mutation in stage II or III disease. The purpose of this study was to assess the prognostic impact of KRAS and BRAF mutation in patients treated with adjuvant 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX).
METHODS: KRAS exon 2 and BRAF codon 600 were analyzed in patients with stage II and III CRC who underwent curative resection followed by adjuvant FOLFOX. Clinicopathologic features and disease-free survival (DFS) were compared.
RESULTS: Among a total of 437 patients, mutational data of KRAS and BRAF were available in 388 and 433 patients, respectively. KRAS mutation (codon 12 and 13) and BRAF V600E mutation was found in 26.5 and 3.7 % of patients. DFS was significantly worse in the KRAS mutant patients compared to KRAS wild type patients (3-year DFS 79 and 92 %, p = 0.006). Multivariate analysis revealed KRAS mutation as an independent negative prognostic factor for DFS (adjusted hazard ratio 2.30, 95 % confidence interval 1.23-4.32). Among the various subtypes of KRAS mutation, G13D (3-year DFS 76 %, p = 0.008) was significantly associated with poor DFS, while G12D was not associated with prognosis (3-year DFS 86 %, p = 0.61). There was no association between BRAF mutation and DFS.
CONCLUSIONS: KRAS mutation has an adverse prognostic impact on stage II or III CRC treated with adjuvant FOLFOX.

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Year:  2014        PMID: 24889488     DOI: 10.1245/s10434-014-3826-z

Source DB:  PubMed          Journal:  Ann Surg Oncol        ISSN: 1068-9265            Impact factor:   5.344


  25 in total

Review 1.  Molecular markers predictive of chemotherapy response in colorectal cancer.

Authors:  Stacey Shiovitz; William M Grady
Journal:  Curr Gastroenterol Rep       Date:  2015-02

2.  KRAS as a predictor of poor prognosis and benefit from postoperative FOLFOX chemotherapy in patients with stage II and III colorectal cancer.

Authors:  Yanhong Deng; Li Wang; Shuyun Tan; George P Kim; Ruoxu Dou; Dianke Chen; Yue Cai; Xinhui Fu; Lei Wang; Jun Zhu; Jianping Wang
Journal:  Mol Oncol       Date:  2015-03-27       Impact factor: 6.603

3.  Nuclear maspin expression correlates with the CpG island methylator phenotype and tumor aggressiveness in colorectal cancer.

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Journal:  Int J Clin Exp Pathol       Date:  2015-02-01

4.  Molecular subtypes in early colorectal cancer associated with clinical features and patient prognosis.

Authors:  M Gil-Raga; E Jantus-Lewintre; S Gallach; V Giner-Bosch; A Frangi-Caregnato; M J Safont-Aguilera; J Garde-Noguera; E Zorraquino-Pina; M García-Martínez; C Camps-Herrero
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Review 5.  RAS signaling and anti-RAS therapy: lessons learned from genetically engineered mouse models, human cancer cells, and patient-related studies.

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Journal:  Acta Biochim Biophys Sin (Shanghai)       Date:  2015-09-07       Impact factor: 3.848

Review 6.  KRAS: A Druggable Target in Colon Cancer Patients.

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Journal:  Int J Mol Sci       Date:  2022-04-08       Impact factor: 6.208

7.  Age-dependent prognostic value of KRAS mutation in metastatic colorectal cancer.

Authors:  Muhammet Ozer; Suleyman Yasin Goksu; Nina Niu Sanford; Chul Ahn; Muhammad Shaalan Beg; Syed Mohammad Ali Kazmi
Journal:  Future Oncol       Date:  2021-11-11       Impact factor: 3.674

8.  KRAS and Combined KRAS/TP53 Mutations in Locally Advanced Rectal Cancer are Independently Associated with Decreased Response to Neoadjuvant Therapy.

Authors:  Oliver S Chow; Deborah Kuk; Metin Keskin; J Joshua Smith; Niedzica Camacho; Raphael Pelossof; Chin-Tung Chen; Zhenbin Chen; Karin Avila; Martin R Weiser; Michael F Berger; Sujata Patil; Emily Bergsland; Julio Garcia-Aguilar
Journal:  Ann Surg Oncol       Date:  2016-03-28       Impact factor: 5.344

9.  Synchronous metastatic colon cancer and the importance of primary tumor laterality - A National Cancer Database analysis of right- versus left-sided colon cancer.

Authors:  Beiqun Zhao; Nicole E Lopez; Samuel Eisenstein; Gabriel T Schnickel; Jason K Sicklick; Sonia L Ramamoorthy; Bryan M Clary
Journal:  Am J Surg       Date:  2019-12-12       Impact factor: 2.565

10.  Image analyzer-based assessment of tumor-infiltrating T cell subsets and their prognostic values in colorectal carcinomas.

Authors:  Younghoon Kim; Jeong Mo Bae; Gang Li; Nam Yun Cho; Gyeong Hoon Kang
Journal:  PLoS One       Date:  2015-04-15       Impact factor: 3.240

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