Use of exosome transcriptome-based analysis to identify novel biomarkers in patients with locally advanced esophageal squamous cell carcinoma undergoing neoadjuvant chemoradiotherapy

BACKGROUND: The prognosis of esophageal squamous cell carcinoma (ESCC) is improved by neoadjuvant chemoradiotherapy (nCRT), especially for patients with pathologic complete response (pCR). Despite the efforts to predict treatment response using multimodality, no molecule has proven to be a strong biomarker. This study aimed to profile the expression of exosome transcriptome that could predict pCR in ESCC before and after nCRT. METHODS: We collected paired blood samples of 15 patients with ESCC who received nCRT and radical surgery. They were divided into 3 groups: (A) residual tumor in the first clinical response evaluation (CRE-1), (B) no residual tumor in CRE-1 but with residual tumor in CRE-2 which was performed after 5–6 weeks, and (C) no residual tumor in CRE-1 or CRE-2. For each patient, the blood sample was collected before nCRT (time point 0); and then 6 weeks after nCRT, the clinical response was evaluated, and another blood sample was collected (time point 1). RESULTS: Using the intersection of different sets, we found 23 progression-associated messenger RNAs (mRNAs) and 67 remission-associated mRNAs. Between remission-associated mRNAs and the targets of progression-associated (carcinogenic) microRNAs (miRNAs), the intersection was acquired, and 2 miRNA-mRNA networks (IFIT2-miR-3615-IFIT2-miR-484 and BTN3A3-miR-6803-3p) were identified. Among the intersection of progression-associated (carcinogenic) mRNAs and the targets of remission-associated miRNAs, there is a network with miR-132-3p (remission-associated miRNA) located at the core, matched with DICER1, KLHL8, ANKRD12, ASH1L, and IMP4. CONCLUSIONS: Our findings identified altered plasma exosome RNAs among the different groups and between different time points of nCRT, as well as the corresponding enrichments and regulatory networks, which may serve as potentially predictors of treatment response for patients with ESCC after nCRT.