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An LSCC-specific R-loop-related model predicts prognosis and neoadjuvant immunotherapy response and identifies
Jie Dai1, Ziyu Qiao1,2, Jia Wang1,2
1Department of Otolaryngology, General Hospital of Northern Theater Command, No.83, Wenhua Road, Shenhe District, Shenyang, 110016, Liaoning, China.
World Journal of Surgical Oncology
|June 20, 2026
Summary
This study developed a new prognostic model for laryngeal squamous cell carcinoma (LSCC) using R-loop-related genes. The model predicts patient outcomes and response to immunotherapy, identifying EIF5A2 as a key immune regulator.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Laryngeal squamous cell carcinoma (LSCC) lacks effective biomarkers for prognosis and predicting immunotherapy response.
- R-loops are implicated in cancer but their role in LSCC is not well understood.
Purpose of the Study:
- To develop an R-loop-related gene signature for prognostic stratification and immunotherapy prediction in LSCC.
- To identify key immune-regulatory genes within the model and elucidate their mechanisms in LSCC.
Main Methods:
- Generated an LSCC-specific R-loop gene set and built a prognostic model using LASSO-Cox regression.
- Validated the model in external cohorts and assessed its relevance for neoadjuvant immunotherapy.
- Utilized single-cell RNA sequencing to identify core immune-regulatory genes and analyze tumor-immune interactions.
Main Results:
- A three-gene R-loop-related model was established, accurately stratifying LSCC patients and showing prognostic value.
- The model predicted immune microenvironment states and response to neoadjuvant immunotherapy.
- EIF5A2 was identified as the core gene, interacting with exhausted CD8 T cells via MIF-CD74 signaling.
Conclusions:
- An LSCC-specific R-loop-related prognostic and immunotherapy prediction model was developed.
- EIF5A2 is a core immune-regulatory gene in LSCC, linking R-loop states to prognosis and immune remodeling.
