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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2022

Open Access 01-12-2022 | Checkpoint Inhibitors | Research

Construction of a predictive model for immunotherapy efficacy in lung squamous cell carcinoma based on the degree of tumor-infiltrating immune cells and molecular typing

Authors: Lingge Yang, Shuli Wei, Jingnan Zhang, Qiongjie Hu, Wansong Hu, Mengqing Cao, Long Zhang, Yongfang Wang, Pingli Wang, Kai Wang

Published in: Journal of Translational Medicine | Issue 1/2022

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Abstract

Background

To construct a predictive model of immunotherapy efficacy for patients with lung squamous cell carcinoma (LUSC) based on the degree of tumor-infiltrating immune cells (TIIC) in the tumor microenvironment (TME).

Methods

The data of 501 patients with LUSC in the TCGA database were used as a training set, and grouped using non-negative matrix factorization (NMF) based on the degree of TIIC assessed by single-sample gene set enrichment analysis (GSEA). Two data sets (GSE126044 and GSE135222) were used as validation sets. Genes screened for modeling by least absolute shrinkage and selection operator (LASSO) regression and used to construct a model based on immunophenotyping score (IPTS). RNA extraction and qPCR were performed to validate the prognostic value of IPTS in our independent LUSC cohort. The receiver operating characteristic (ROC) curve was constructed to determine the predictive value of the immune efficacy. Kaplan–Meier survival curve analysis was performed to evaluate the prognostic predictive ability. Correlation analysis and enrichment analysis were used to explore the potential mechanism of IPTS molecular typing involved in predicting the immunotherapy efficacy for patients with LUSC.

Results

The training set was divided into a low immune cell infiltration type (C1) and a high immune cell infiltration type (C2) by NMF typing, and the IPTS molecular typing based on the 17-gene model could replace the results of the NMF typing. The area under the ROC curve (AUC) was 0.82. In both validation sets, the IPTS of patients who responded to immunotherapy were significantly higher than those who did not respond to immunotherapy (P = 0.0032 and P = 0.0451), whereas the AUC was 0.95 (95% CI = 1.00–0.84) and 0.77 (95% CI = 0.58–0.96), respectively. In our independent cohort, we validated its ability to predict the response to cancer immunotherapy, for the AUC was 0.88 (95% CI = 1.00–0.66). GSEA suggested that the high IPTS group was mainly involved in immune-related signaling pathways.

Conclusions

IPTS molecular typing based on the degree of TIIC in the TME could well predict the efficacy of immunotherapy in patients with LUSC with a certain prognostic value.
Appendix
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Metadata
Title
Construction of a predictive model for immunotherapy efficacy in lung squamous cell carcinoma based on the degree of tumor-infiltrating immune cells and molecular typing
Authors
Lingge Yang
Shuli Wei
Jingnan Zhang
Qiongjie Hu
Wansong Hu
Mengqing Cao
Long Zhang
Yongfang Wang
Pingli Wang
Kai Wang
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-022-03565-7

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