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Investigation and verification of GIMAP6 as a robust biomarker for prognosis and tumor immunity in lung adenocarcinoma

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Abstract

Background and aim

According to previous reports, GTPase of immunity-associated protein 6 (GIMAP6) is essential for autophagy. However, it is unclear how GIMAP6 affects the development and tumor immunity of lung adenocarcinoma (LUAD).

Methods

In the present study, the role of GIMAP6 in vivo and in vitro was examined using reverse transcription-quantitative PCR, western blotting, and Cell Counting Kit-8, colony formation and Transwell assays. Datasets from The Cancer Genome Atlas and Genotype-Tissue Expression databases were thoroughly analyzed using R software. A nomogram was created using GIMAP6 and prognostic characteristics. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and Gene Set Enrichment Analysis were applied to explore the potential mechanism of GIMAP6 in lung cancer. The link between GIMAP6 and the immunological landscape was studied using single-cell RNA sequencing datasets from Tumor Immune Estimation Resource (TIMER) 2.0 and Tumor Immune Single-cell Hub.

Results

Patients with high GIMAP6 expression had improved overall and disease-specific survival compared with those patients with low GIMAP6 expression. According to the receiver operating characteristic and calibration curve, the nomogram based on T stage, N stage and GIMAP6 had predictive value for prognosis. According to functional enrichment analysis, GIMAP6 was primarily involved in T-cell receptor signaling pathway, chemokine signaling pathway, cytokine and cytokine receptor interaction. GIMAP6 was shown to be favorably linked with the infiltration of immune cells and immune-related molecules, including cytotoxic T-lymphocyte associated protein 4, programmed death-ligand 1, and T cell immunoreceptor with Ig and ITIM domains, by single-cell sequencing and TIMER2.0 analysis. The role of GIMAP6 in lung cancer cell proliferation, invasion, migration and immunity was experimentally verified.

Conclusion

These findings confirmed that GIMAP6 was an effective prognostic molecule that was involved in the regulation of the immune microenvironment of LUAD, and may become a predictor for the efficacy of immunotherapy.

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Acknowledgements

We thank Tianjin Medical University Cancer Institute and Hospital for providing us with pathological specimens.

Funding

This present research was funded by the National Natural Science Foundation of China (to Richeng Jiang) (No. 82172620).

Author information

Author notes

  1. Xiuqiong Chen and Zhaona Li have share first authorship.

Authors and Affiliations

  1. Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China

    Xiuqiong Chen, Zhaona Li, Xinyue Wang, Jing Zhou, Qianhui Wei, Kaidi Chen & Richeng Jiang

  2. Key Laboratory of Cancer Prevention and Therapy, Tianjin, China

    Xiuqiong Chen, Zhaona Li, Xinyue Wang, Jing Zhou, Qianhui Wei, Kaidi Chen & Richeng Jiang

  3. Tianjin’s Clinical Research Center for Cancer, Tianjin, China

    Xiuqiong Chen, Zhaona Li, Xinyue Wang, Jing Zhou, Qianhui Wei, Kaidi Chen & Richeng Jiang

  4. Department of Thoracic Oncology, Tianjin Lung Cancer Center, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, People’s Republic of China

    Xiuqiong Chen, Zhaona Li, Xinyue Wang, Jing Zhou, Qianhui Wei, Kaidi Chen & Richeng Jiang

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  1. Xiuqiong Chen
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Contributions

XC and ZL: conceptualization, methodology, validation, formal analysis, writing-original draft. XC and JZ: software, validation, formal analysis. XW and JZ: software, validation, formal analysis. XC and QW: investigation, resources. XC, ZL, XW, JZ, QW, and KC: investigation, resources. RJ and XW: supervision. ZL: conceptualization, writing—review and editing, funding acquisition.

Corresponding author

Correspondence to Richeng Jiang.

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Conflict of interest

The authors declared that they have no competing interests.

Ethical approval

This study was approved by the institutional Ethics Committee of Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin, China (approval number was bc2022263).

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Chen, X., Li, Z., Wang, X. et al. Investigation and verification of GIMAP6 as a robust biomarker for prognosis and tumor immunity in lung adenocarcinoma. J Cancer Res Clin Oncol 149, 11041–11055 (2023). https://doi.org/10.1007/s00432-023-04980-z

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  • DOI: https://doi.org/10.1007/s00432-023-04980-z

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