Background: Colorectal cancer (CRC) patients with different molecular phenotypes, including microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and somatic mutations in BRAF  and KRAS  gene, vary in treatment response and prognosis. However, molecular phenotyping under adequate quality control in a community-based setting may be difficult. We aimed to build the nomograms based on easily accessible clinicopathological characteristics to predict molecular phenotypes.
Methods: Three hundred and six patients with pathologically confirmed stage I-IV CRC were included in the cohort. The assays for MSI, CIMP, and mutations in BRAF  and KRAS  gene were performed using resected tumor samples. The candidate predictors were identified from clinicopathological variables using multivariate Logistic regression analyses to construct the nomograms that could predict each molecular phenotype.
Results: The incidences of MSI, CIMP, BRAF  mutation and KRAS  mutation were 25.3% (72/285), 2.5% (7/270), 3.4% (10/293), and 34.8% (96/276) respectively. In the multivariate Logistic analysis, poor differentiation and high neutrophil/lymphocyte ratio (NLR) were independently associated with MSI; poor differentiation, high NLR and high carcinoembryonic antigen/tumor size ratio (CSR) were independently associated with CIMP; poor differentiation, lymphovascular invasion and high CSR were independently associated with BRAF  mutation; poor differentiation, proximal tumor, mucinous tumor and high NLR were independently associated with KRAS  mutation. Four nomograms for MSI, CIMP, BRAF  mutation and KRAS  mutation were developed based on these independent predictors, the C-indexes of which were 61.22% (95% CI: 60.28– 62.16%), 95.57% (95% CI: 95.20– 95.94%), 83.56% (95% CI: 81.54– 85.58%), and 69.12% (95% CI: 68.30– 69.94%) respectively.
Conclusion: We established four nomograms using easily accessible variables that could well predict the presence of MSI, CIMP, BRAF  mutation and KRAS  mutation in CRC patients.
Keywords: colorectal cancer, microsatellite instability, CpG island methylator phenotype, BRAF , KRAS , nomogram, prediction of molecular subtypes