GBP5 Expression Predicted Prognosis of Immune Checkpoint Inhibitors in Small Cell Lung Cancer and Correlated with Tumor Immune Microenvironment

Abstract

Background

The discovery and development of immune checkpoint inhibitors (ICIs) has significantly enhanced the arsenal of immunotherapy treatments available for cancer patients. The identification of biomarkers that are indicative of an individual’s sensitivity to treatment with ICIs is useful for screening SCLC patients prior to commencement of any ICIs based immunotherapy. However, the relationship between GBP5 and the prognosis of SCLC immunotherapy is still unclear and requires further study.

Methods

We downloaded two SCLC datasets, namely the George-SCLC and Jiang-SCLC cohorts. We used the TIDE algorithm to predict the efficacy of immunotherapy for SCLC patients. The QuanTIseq, MCPcounter, and EPIC algorithms are used to calculate the proportions of immune cells in SCLC patients. Additionally, we retrospectively collected 35 SCLC samples from the first affiliated hospital of the Hengyang Medical school.

Results

Patients in each cohort were devided into two groups with high (GBP5-High) and low (GBP5-Low) expression of GBP5. In both cohorts, the GBP5-High population had a higher proportion of patients that responded well to immunotherapy (responders) (p < 0.05). In addition, both GBP5-High subgroups had significantly increased cytotoxicity, chemokines, antigen presenting, and TNF family related genes. We also determined that GBP5 was related to high-level infiltration of B cells, CD4+T cells, CD8+T cells and NK cells.

Conclusion

In this study, we found that GBP5 has the potential to be used as a biomarker of ICIs efficacy for SCLC patients. GBP5 is related to the quantity of inflammatory molecules, a high level of immune infiltration, and a highly activated immune response pathway.

Keywords:

• GBP5
• small cell lung cancer
• prognosis
• tumor immune microenvironment
• immune checkpoint inhibitors

Data Sharing Statement

All the data generated or analyzed during this study are included in this article and its Supplementary Files.

Ethics Statement

The patients/participants provided their written informed consent to participate in this study and the research presented here has been performed in accordance with the Declaration of Helsinki and has been approved by the ethics committee of the first affiliated hospital of the Hengyang Medical school, University of South China.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Additional information

Funding

This work was supported by Project of Natural Science Foundation of Hunan Province (Grant No.2021JJ30622, 2021JJ70041), Clinical Medical Technology Innovation Guidance Project of Hunan Province (Grant No.2021SK51808, 2021SK51827), Project of Health Commission of Hunan Province (Grant No.20201992), Scientific Research Fund of Education Department of Hunan Province (Grant No.21B0430), The second batch of technological innovation plan projects of Hengyang City in 2021 (Study on the Mechanism of MYCN Targeting HES1 to Regulate Stem Cells and Chemotherapy Resistance of Small Cell Lung Cancer), Joint Funds for the Innovation of Science and Technology of Fujian Province, China (Grant No.2020Y9026).