Abstract
We report a pilot study on the feasibility of determinations of circulating levels of paraoxonase-1 (PON1) and compounds related to energy metabolism as biomarkers for the evaluation of patients with rectal cancer (RC), and the effects produced by neoadjuvant radiochemotherapy (NRCT). We studied 32 patients treated with radiotherapy plus capecitabine concomitant chemotherapy and 48 control subjects. We identified pre-NRCT PON1 and α-ketoglutarate as the parameters that best discriminated between RC patients and the control group. Receiver operating characteristics analysis of the combination of the two parameters showed an area under the curve (AUC) of 0.918. Moreover, patients who presented a pathological complete response (pCR) to treatment had lower plasma pre-NRCT valine concentrations (AUC of 0.826). Patients who had a relapse had lower concentrations of succinate (AUC of 0.833). The results of the present study illustrate the usefulness of investigating alterations in oxidative stress and metabolism in RC. Due to the small number of patients studied, our results must be considered preliminary, but they suggest that the determination of circulating levels of PON1 and α-ketoglutarate might be a valuable tool for the early diagnosis of RC, while the determination of valine and succinate might effectively predict pCR and the appearance of relapse.
Highlights
Rectal cancer (RC) is the eighth most common cancer worldwide
Serum PON1 activity correlated to some energy balance-related metabolites, which could be a reflection of the peripheral circulation of the protective effect of this enzyme on the mitochondria or that alterations in mitochondrial metabolism affect the activity of the enzyme both within the cell and in circulation, as it has been described in other chronic diseases [32]
An increase in oxidative stress, such as that produced by Neoadjuvant radiochemotherapy (NRCT), would be associated with a partial decrease in PON1 activity, which does not correlate with the increase in its concentration
Summary
Rectal cancer (RC) is the eighth most common cancer worldwide. It is associated with high mortality and morbidity, and is becoming increasing prevalent in young individuals. Neoadjuvant radiochemotherapy (NRCT) is the standard treatment for patients with this disease [1,2,3,4]. Data on the effects of this treatment on metabolism is scarce.
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