Abstract

BackgroundTo investigate the differences in plasma metabolomic characteristics between pathological complete response (pCR) and non-pCR patients and identify biomarker candidates for predicting the response to neoadjuvant chemoradiotherapy (nCRT) in esophageal squamous cell carcinoma (ESCC).MethodsA total of 46 ESCC patients were included in this study. Gas chromatography time-of- flight mass spectrometry (GC-TOF/MS) technology was applied to detect the plasma samples collected before nCRT via untargeted metabolomics analysis.ResultsFive differentially expressed metabolites (out of 109) was found in plasma between pCR and non-pCR groups. Compared with non-pCR group, isocitric acid (p = 0.0129), linoleic acid (p = 0.0137), citric acid (p = 0.0473) were upregulated, while L-histidine (p = 0.0155), 3′4 dihydroxyhydrocinnamic acid (p = 0.0339) were downregulated in the pCR plasma samples. Pathway analyses unveiled that citrate cycle (TCA cycle), glyoxylate and dicarboxylate metabolic pathway were associated with ESCC chemoradiosensitivity.ConclusionThe present study provided supporting evidence that GC-TOF/MS based metabolomics approach allowed identification of metabolite differences between pCR and non-pCR patients in plasma levels, and the systemic metabolic status of patients may reflect the response of ESCC patient to neoadjuvant chemoradiotherapy.

Highlights

  • We aim to investigate the differences in plasma metabolomic characteristics between pathological complete response (pCR) and non-pCR patients and identify biomarker candidates for predicting the response to neoadjuvant chemoradiotherapy in esophageal squamous cell carcinoma (ESCC)

  • The results showed that five metabolites demonstrated differences between pCR and non-pCR patients in the plasma collected before the onset of neoadjuvant therapy

  • This study provided supporting evidence that GC-TOF/Liquid chromatography mass spectrometry (MS) based metabolomics approach allowed identification of metabolite differences between pCR and non-pCR patients in plasma levels, and the systemic metabolic status of patients may reflect the response of ESCC to neoadjuvant chemoradiotherapy

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Summary

Introduction

To investigate the differences in plasma metabolomic characteristics between pathological complete response (pCR) and non-pCR patients and identify biomarker candidates for predicting the response to neoadjuvant chemoradiotherapy (nCRT) in esophageal squamous cell carcinoma (ESCC). Over 50% of all EC-related deaths occur in China where esophageal squamous cell carcinoma (ESCC) is the predominant histologic subtype [2]. Surgery is the primary treatment of esophageal cancer, especially for patients with early stage [3, 4]. Most esophageal cancer cases has progressed to advanced stage before they are diagnosed [5]. Neoadjuvant chemoradiotherapy (nCRT) has been considered as a promising therapy strategy for patients with stage II or III esophageal cancer. It is essential to find a reliable marker of chemoradiosensitivity in esophageal cancer to avoid wasting valuable time and obtain a more favorable prognosis for patients

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