Exploring potential biomarkers of early stage esophageal squamous cell carcinoma in pre- and post-operative serum metabolomic fingerprint spectrum using 1H-NMR method.

ABSTRACT

Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent types of upper gastrointestinal malignancy. Here, we used 1H nuclear magnetic resonance spectroscopy (1H-NMR) to identify potential pre- and post-operative serum biomarkers in patients with early stage ESCC using metabolomic fingerprint spectrum. Serum samples from preoperative patients with ESCC (ESCC, n = 25), postoperative patients with ESCC (PO, n = 24), and controls (n = 40) were analysed using 1H-NMR spectroscopy. Using orthogonal partial least squares-discriminant analysis, 31 altered serum metabolites were successfully identified among the three groups. These metabolites are indicative of the changes that occur with glycometabolism, the metabolism of fatty acids, amino acids, choline, ketone bodies, nucleotides, and lipids. Based on receiver operating characteristic (ROC) curve analysis and a biomarker panel with an area under the curve (AUC) of 0.969, six serum metabolites (α-glucose, choline, glutamine, glutamate, valine, and dihydrothymine) were selected as potential diagnostic biomarkers for early stage ESCC. Additionally, four potential PO biomarkers (α-glucose, pyruvate, glutamate, and valine) with an AUC of 0.985 were selected to distinguish ESCC and PO. Many metabolites trended towards normalisation in PO patients, with only choline remaining high with an AUC of 0.858, suggesting that it may be a valuable potential biomarker for neoplasm progression, recurrence, chemoradiotherapy, and prognosis. 1H-NMR spectroscopy may be a useful tumour detection approach in the early diagnosis of ESCC. These results also indicate that it is useful to differentiate pre- and post-operative ESCC, evaluate surgery therapeutic responses, and monitor postoperative chemoradiotherapy.