Independent prognostic biomarker FERMT3 associated with immune infiltration and immunotherapy response in glioma

Abstract

Background

Adult glioma progresses rapidly and has a poor clinical outcome. The focal adhesion protein Kindlin-3 (encoded by the FERMT3 gene) participates in tumor development, drug resistance, and progression. However, the relationship between Kindlin-3 and glioma prognosis or immune microenvironment is poorly understood.

Methods

We comprehensively analyzed the expression, prognostic value, mutation landscape, functional enrichment, immune infiltration, and therapeutic role of FERMT3 in glioma using multiple datasets and validated Kindlin-3 expression in clinical tissue specimens by immunohistochemistry and multiple immunofluorescence staining.

Results

FERMT3 is an independent predictor of glioma prognosis and is highly expressed in glioblastoma tissues. Functional enrichment analyses indicated that FERMT3 participates in multiple immune-related pathways such as immune response and cytokine production. Furthermore, FERMT3 expression was positively correlated with the infiltration of several immune cells, immune scores, and the expression of genes related to immune checkpoints. Further analyses revealed that overexpression of FERMT3 was linked to a better response to anti-PD1 therapy. Data from single-cell RNA-seq reveal that FERMT3 was largely expressed in microglial cells and tissue-resident macrophages. Multiple immunofluorescence staining confirmed the overexpression of Kindlin-3 in the glioma-associated microglia/macrophages (GAMs).

Conclusion

The findings of this study provide a new perspective on the role of Kindlin-3 in glioma and may have a significant impact on the discovery of novel biomarkers and targeting of GAMs in the future.

Keywords:

• Glioma
• FERMT3
• prognosis
• tumor immune microenvironment
• immunotherapy

Acknowledgments

The authors gratefully acknowledge contributions from the CGGA, TCGA network, and other multiple databases used in this manuscript and sincerely thank the Home for Researchers editorial team for the language polishment.

Author contributions

KY and KW conceived and designed the study. SZ, CT, and LY contributed equally to the experimentation, data analysis, and manuscript writing. ZC and TC revised the manuscript. The final manuscript has been read and approved by all authors.

Ethics approval

The study methodologies conformed to the standards set by the Declara-tion of Helsinki. The studies involving human participants were reviewed and approved by the Medical Ethics Committee of the First Affiliated Hospital of Hainan Medical University (Approval number: 2022 (Scientifc Research L) No. (144)).

Patient consent

All participants were provided with written informed consent.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets presented in this study can be found in in the CGGA database (http://www.cgga.org.cn/).

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by the Finance Science and Technology Project of Hainan Province (Grant No. ZDYF2022SHFZ088), the National Nature Science Foundation of China (Grant No. 82060456), Hainan Provincial Natural Science Foundation of China (Grant No. 821MS137), the Innovative Research Project of Hainan Graduate Students (Grant No. Qhyb2021-58) and Hainan Province Clinical Medical Center.