Molecular subtypes in early colorectal cancer associated with clinical features and patient prognosis
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After surgical resection, an ample prognosis variability among stages is observed. Multiple prognostic factors are individually studied and some CRC classifiers have been proposed. Not one have been implemented into clinical practice.
We classified 105 patients with resected CRC (stage I–III) into five molecular subtypes using BRAF V600E and RAS (KRAS; NRAS) status, and the expression of DNA mismatch repair (MMR) proteins (MLH1 and MSH2). Clinicopathological features and DFS) of distincts groups were evaluated.
Results and conclusions
RAS and BRAFV600E mutations were detected in 43.8 and 11.4% of patients, respectively. 19% of tumours had lack of expression of any MMR proteins reflecting a system deficiency (dMMR). Patients with any RAS mutation had lower DFS that patients with RAS wild type (wt) (40.23 vs 45.26 months; p value = 0.035). Of a total of five molecular subtypes, three were MMR proficient (pMMR): RAS mutated (39%), BRAFV600E mutated (6.7%) and RAS/BRAFV600E wt (35.2%); and two were dMMR: BRAFV600E mutated (4.8%) and BRAFV600E wt (14.3%). Left side tumours were more frequently observed in pMMR/RAS and BRAFV600E wt subtype, and right side tumours in dMMR subtypes. Among the three pMMR subtypes, a benefit survival was observed for patients without any mutation in BRAF v600E or RAS oncogenes (median of DFS = 45.5 vs 40.98 months in RAS mutated group; p = 0.084 and vs 34.13 in BRAF v600E mutated group; p = 0.031). Molecular classification using these biomarkers can be useful to identify groups with differences in prognosis.
KeywordsColorectal cancer Prognostic factor Molecular subtypes
Compliance with ethical standards
Conflict of interest
All authors declare that they have no competing interest.
Research involving human participants and/or animals/ethical approval
All procedures performed in studies involving human participants were in accordance with the Clinical Research Ethics Committee of General University Hospital of Valencia and by The Research Committee of Hospital of Sagunto, in accordance with the Declaration of Helsinki (1964), the Good Clinical Practices and local ethical and legal requirements (Spanish laws). This study complied with all applicable regulations for human participant studies. All authors reviewed and approved the final manuscript.
Prior to study entry, all patients provided written informed consent according to the local ethics committee regulations.
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