Immune Score Indicator for the Survival of Melanoma Patients Based on Tumor Microenvironment

Abstract

Background

Tumor microenvironment (TME) refers to the cellular environment where tumors exist, including immune cells, fibroblasts, stromal cells, chemokines, etc. TME is closely related to the prognosis of various tumors; nevertheless, limited studies have established predictive prognosis models based on TME. This work aims to construct a survival prediction model for melanoma patients based on TME.

Methods

Data of 482 melanoma patients were extracted from The Cancer Genome Atlas (TCGA) database. Based on the infiltration of immune cells (Immune score), stromal cells (Stromal score), and tumor purity (Estimate score), the “Estimate” algorithm was used to construct 3 scores for each patient. To identify the differentially expressed genes (DEGs), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using DAVID database and visualized using the R software. The STRING database was used to construct the protein-protein interaction (PPI) network and functional modules. FGD2 expression was confirmed via Western Blotting and quantitative reverse transcription PCR (RT-qPCR) analyses.

Results

Patients with higher immune scores estimate scores showed better OS than those with lower scores. All three scores were related to age and primary tumor stage. Further, DEGs between patients with high immune/stromal scores and low immune/stromal scores were screened. Eventually, 10 down-regulated DEGs and 201 up-regulated DEGs were identified as TME associated genes. Out of these, the FGD2 gene demonstrated close association with survival and was confirmed in the included melanoma patients.

Conclusion

In summary, TME is closely associated with the prognosis of melanoma patients. Besides, genes including FGD2 promote the TME-mediated regulation of melanoma.

Keywords:

• tumor microenvironment
• the cancer genome atlas
• melanoma
• FGD2

Data Sharing Statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Ethics Approval and Consent to Participate

All patients provided and signed informed consents. The study was approved by the Ethical Committee of the Affiliated Hospital of Qingdao University and experiments were performed as per the Ethical Committee’s guidelines and regulations. All procedures involving human participants were performed based on the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Acknowledgments

The results here are in part based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga.

Author Contributions

All authors made a significant contribution to the work reported, including in the conception, study design, execution, data acquisition, analysis, and interpretation. Also, the authors participated in drafting, revising, or critically reviewing the article; provided final approval of the version to be published; agreed on the journal to which the article has been submitted, and remain accountable for all aspects of the work. Xuchao Ning and Renzhi Li equally contributed to this paper.

Disclosure

The authors declare no conflicts of interest concerning the publication of this article.

Additional information

Funding

This study was supported by the Application of excipients loaded with platelet plasma in wound healing (Grant No.3457) and Qingdao Science and Technology Development Plan (Grant No.1651).