Serum metabolite levels identify incipient metastatic progression of rectal cancer.

backgroundThe cellular metabolism undergoes reprogramming during the metastatic process. We hypothesised that serum metabolites at the time of primary tumour diagnosis might identify rectal cancer patients prone to metastatic progression.

methodsOne hundred twenty-three rectal cancer patients from a prospective observational biomarker study were followed up to 5 years after study entry. We have assessed metabolites in serum sampled at the time of diagnosis by

resultsHere we show that patients who develop overt metastatic disease more than 6 months after the primary tumour diagnosis have elevated serum levels (Kruskal-Wallis test) of alanine (P = 0.005), lactate (P = 0.023), pyruvate (P = 0.041) and citrate (P = 0.007) compared to those without metastases at the 5-year follow-up or with metastases already 6 months or sooner after the cancer diagnosis. Patients with serum citrate above 0.24 mmol/L have poorer progression-free survival compared to those with levels below (P < 0.001; log-rank test).

conclusionsWe observe a distinct serum metabolite profile, in particular involving citrate to the best of our knowledge shown for the first time clinically, in rectal cancer patients at heightened risk of metastasis already when the primary tumour is diagnosed, offering insights into the metabolism of metastatic progression.