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Comprehensive analysis of the lncRNAs-related immune gene signatures and their correlation with immunotherapy in lung adenocarcinoma

British Journal of Cancer volume 129, pages 1397–1408 (2023)Cite this article

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Abstract

Background

Long non-coding RNAs (lncRNAs)-related immune genes (lrRIGs) play a crucial role in the development and progression of lung adenocarcinoma (LUAD). However, reliable prognostic signatures based on lrRIGs have not yet been identified.

Methods

We screened lrRIGs associated with the prognosis of LUAD using The Cancer Genome Atlas (TCGA) database and then established a novel prognostic nine-gene signature composed of CD79A, INHA, SHC3, LIFR, TNFRSF11A, GPI, F2RL1, SEMA7A and WFDC2 through bioinformatic approaches. A risk score derived from this gene signature was used to divide LUAD patients into the low- and high-risk groups. The latter was confirmed to have markedly worse overall survival (O.S.). A nomogram was developed using the risk score and other independent prognostic elements, demonstrating excellent performance in predicting the O.S. rate of LUAD patients.

Results

We observed that the infiltration of diverse immune cell subtypes and response to immunotherapy and chemotherapy significantly differed between the low- and high-risk groups.

Conclusions

Overall, stratification based on this gene signature could be used to guide better therapeutic management and improve outcomes for LUAD patients.

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Fig. 1: Identifying prognostic risk genes and analyzing their expression based on differentially expressed lncRNA-related immune genes (DE-lrRIGs) using the TCGA_LUAD database.
Fig. 2: Prognostic performance of the lrRIGs signature.
Fig. 3: Association between indicated variables and prognosis of patients with LUAD.
Fig. 4: Comparison of immune microenvironments between high- and low-risk groups defined by the 9-gene signature.
Fig. 5: Analysis of immune checkpoints, HLA and mismatch repair genes expression and TMB.
Fig. 6: Predicted patients' response in TCGA database to targeted therapies and standard chemotherapies in different risk groups.
Fig. 7: To investigate the possible mechanism of prognostic signature gene GPI affecting the prognosis of LUAD patients.

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Data availability

Relevant research data have been presented in the text. All data will be provided upon request if necessary.

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Acknowledgements

We sincerely acknowledge the contributions from the TCGA, GEO, innateDB, GDSC and GSEA databases. This work was supported by the National Natural Science Foundation of China (Nos. 81372147, 81803575, 31902287), Henan University support grant CX3070A0780502, the Key Science and Technology Research and Development and Promotion Special Project of Henan Province (No. 232102311205), and the Key R&D and promotion projects of Kaifeng (No. 2203008).

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  1. These authors contributed equally: Zhengyan Yang, Jianling Zhu.

Authors and Affiliations

  1. Joint National Laboratory for Antibody Drug Engineering, the First Affiliated Hospital, School of Basic Medical Sciences, Henan University, Kaifeng, China

    Zhengyan Yang, Jianling Zhu, Tiantian Yang, Wenjun Tang, Zhiguang Ren & Feng Lu

  2. Department of Immunology, School of Basic Medical Sciences, Henan University, Kaifeng, China

    Jianling Zhu, Tiantian Yang, Wenjun Tang & Feng Lu

  3. Department of Clinical Laboratory, Puyang Hospital of Traditional Chinese Medicine, Puyang, China

    Xiaowei Zheng

  4. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, China

    Shaoping Ji

  5. Institute of Traditional Chinese Medicine, Henan University, Kaifeng, China

    Zhiguang Ren

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Contributions

FL conceived and designed this article. ZY, JZ, TY, WT, and XZ participated in the experimental data collection; SJ provided technical assistance; FL drafted the manuscript; ZR revised the study draft. All authors contributed to the article and approved the submitted version.

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Correspondence to Zhiguang Ren or Feng Lu.

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The studies involving human participants were reviewed and approved by the Ethics Committee of Medical School of Henan University, China (HUSOM-2018-282). Informed consent was obtained from all subjects involved in the study.

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Cell Culture and Stable Transfection of shRNA

41416_2023_2379_MOESM3_ESM.xlsx

Table S1. The clinicopathologic characteristics of 30 matched clinical LUAD samples employed for Western blot assay of protein expression of candidate genes.

Table S2. The antibodies used in this study.

Table S3. Immune-related genes matrix based on TCGA_LUAD database.

Table S4. A total of 889 lncRNAs-related immune genes (lrRIGs) were identified.

Table S5. 329 differentially expressed lncRNAs-related immune genes were identified.

41416_2023_2379_MOESM8_ESM.xlsx

Table S6. 27 lncRNAs-related immune genes were significantly associated with the OS of LUAD patients through univariate Cox regression analysis.

41416_2023_2379_MOESM9_ESM.xlsx

Table S7. Nine genes were screened to construct a significant prognostic signature by multivariate Cox regression analysis.

41416_2023_2379_MOESM10_ESM.xlsx

Table S8. Gene Set Enrichment Analysis (GSEA) was performed by comparing the high expression and low expression of the GPI gene based on the TCGA_LUAD, GSE31210, GSE68465 and GSE13213 databases.

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Yang, Z., Zhu, J., Yang, T. et al. Comprehensive analysis of the lncRNAs-related immune gene signatures and their correlation with immunotherapy in lung adenocarcinoma. Br J Cancer 129, 1397–1408 (2023). https://doi.org/10.1038/s41416-023-02379-8

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