D20Serum metabolomic as biomarkers to differentiate early from metastatic disease in elderly colorectal cancer (crc) patients

Background: Adjuvant chemotherapy improves survival in stage II and III CRC, although a significant proportion of patients are cured by surgery alone. Improved risk stratification is required to reduce the number of patients treated unnecessarily, particularly in elderly populations at risk for higher toxicity. Serum metabolomic profiles may act as biomarkers of residual (micrometastatic) disease, a prerequisite for relapse, and have been prognostic in other tumor types. This study aims to (1) identify in elderly patients a metabolomic “signature” for metastatic disease (mCRC) that differentiates it from early disease (eCRC) and (2) create a metabolomic index for eCRC patients that correlates with clinical outcomes and may be predictive for relapse. Materials & methods: Serum samples from 103 elderly patients (aged ≥ 70 years) with CRC (48 mCRC and 55 eCRC with ≥ 5 years follow-up) were pooled from 4 previous clinical trials. Samples were analyzed via Proton Nuclear Magnetic Resonance (NMR) and the spectra were used to characterize the metabolic profiles of the two cohorts. Principal component analysis (PCA) and canonical analysis (CA) were applied to obtain the supervised separation of eCRC and mCRC spectra. The K-nearest neighbors (k-NN) method was applied to the PCA-CA scores, for classification. Wilcoxon signed-rank test was then used to compare the levels of 34 quantified metabolites between eCRC and mCRC patients. Results: The median age was 78 years (range 70-89) for eCRC and 77 years (range 70-87) for mCRC. There were 4%, 49%, and 47% comprising stage I, II, and III, respectively. Around 44% (n = 24) received adjuvant chemotherapy and 27% (n = 15) had relapsed. PCA-CA-kNN classification of NMR spectra was able to discriminate eCRC and mCRC with an accuracy of 74%. A clear distinction was noted between eCRC without relapse and mCRC. Four metabolites (2-methylbutyrate, 2-methylsuccinate, histidine and formate) were found to differ significantly (p < 0.05) between eCRC and mCRC metabolomic profiles. Conclusion: NMR metabolomic profiles can discriminate early and metastatic CRC in elderly patients. Next, our team will work on a model to assess the likelihood of relapse, based on the degree an eCRC serum profile resembles the metastatic profiles and correlate this with clinical outcomes.