A novel immune-related prognostic signature based on Chemoradiotherapy sensitivity predicts long-term survival in patients with esophageal squamous cell carcinoma

BACKGROUND: There is a heterogenous clinical response following chemoradiotherapy (CRT) in esophageal squamous cell carcinoma (ESCC). Therefore, we aimed to study signaling pathway genes that affect CRT sensitivity and prognosis. METHODS: Gene expression analyses were performed in the GEO and TCGA datasets. A immunohistochemistry (IHC) analysis was performed in pretreatment biopsies. RESULTS: MMP13 was found to be highly expressed in the “Pathologic Complete Response (pCR)” and “Complete Remission (CR)” and “Alive” groups. Th17 cells and MMP9/13 showed a negative correlation in immune infiltration analysis. In GSEA analysis, IL-4 and IL-13 signaling pathways were highly enriched in patients exhibiting high MMP expression in pCR and CR groups. IHC results suggested higher MMP13 & IL-4 and lower IL-17A & RORC expression in the CR group compared to the <CR (CR not achieved) group. Survival analyses further indicated that the prognosis was worse in the high IL-17A group (p = 0.046, HR = 2.15). Next, a prognostic model was established. In the training cohort, AUCs for the 1/2/3/4/5-year OS were all greater than 0.70. In the two validation cohorts, 1-year AUCs were also >0.70, and the model could well distinguish high-risk and low-risk subgroups. CONCLUSION: The above results may provide guidance for developing novel treatment and prognostic strategies in ESCC patients.