Background: Currently, there are insufficient indicators for the reliable assessment of treatment response following neoadjuvant chemoradiotherapy (nCRT) in patients with esophageal squamous cell carcinoma (ESCC). Considering the essential role of protein-coding and non-coding RNAs in gene regulation and cellular processes, we systematically explored the molecular features and clinical significance of mRNA and lncRNA in 249 pretreatment biopsies from four hospitals in three districts with a high incidence of ESCC patients in China.
Methods: During the discovery phrase, 13 differentially expressed genes were identified and validated between samples with a complete pathological response (pCR) and those with an incomplete pathological response (<pCR). Subsequently, we constructed a predictive mRNA and lncRNA signature (SERPINE1, LINC00592, and PRKAG2-AS1) using Fisher's linear discriminant analysis (FLDA) with stepwise variant-selection, followed by validation of its predictive ability in both internal and external cohorts.
Results: Our signature showed great value in predicting the response to nCRT among ESCC samples and acted as an independent predictive indicator, in addition to demonstrating great potential in estimating patient prognosis. Interestingly, we found that patients with a high signature score had lower PD-L1 and IDO1 expression levels but higher CD8+ T cells infiltration, suggesting that PD-L1 and IDO1 are negatively correlated with a high signature score and further associated with pCR and a better prognosis.
Conclusion: The present study identified a promising three-gene-based predictive signature that has powerful clinical implications for the identification of pCR and a good prognosis among patients with ESCC. Further immune-related exploration may provide an opportunity for future therapeutic combination.
Keywords: Esophageal squamous cell carcinoma; Immune microenvironment; Neoadjuvant chemoradiotherapy; Prognosis prediction; Therapeutic response.
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