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

PeerJ. 2023 Aug 18:11:e15839. doi: 10.7717/peerj.15839. eCollection 2023.

Abstract

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.

Keywords: Chemoradiotherapy sensitivity; Differential expression genes; Esophageal squamous cell carcinoma; Interleukins; Neoadjuvant chemoradiotherapy; Prognosis; Signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemoradiotherapy
  • Esophageal Neoplasms* / genetics
  • Esophageal Squamous Cell Carcinoma* / genetics
  • Humans
  • Interleukin-17 / genetics
  • Interleukin-4
  • Matrix Metalloproteinase 13
  • Prognosis

Substances

  • Interleukin-17
  • Interleukin-4
  • Matrix Metalloproteinase 13

Grants and funding

This work was supported by the 2022 Science and Technology Plan Projects of Ordos Municipal Bureau of Science and Technology (No. 2022YY014), the Natural Science Foundation of China (No. 81874220) and the Natural Science Foundation of Guangdong Province (No. 2022A1515012483 and No. 2020A1515010030). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.