A novel immune-related prognostic signature based on Chemoradiotherapy sensitivity predicts long-term survival in patients with esophageal squamous cell carcinoma
Zewei Zhang, Shiliang Liu, Tiantian Gao, Yuxian Yang, Quanfu Li, Lei Zhao- General Agricultural and Biological Sciences
- General Biochemistry, Genetics and Molecular Biology
- General Medicine
- General Neuroscience
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.