J Cancer 2020; 11(17):5245-5256. doi:10.7150/jca.46383

Research Paper

Prognostic implication and functional annotations of APOBEC3G expression in patients with Melanoma

Wei Han1,2#, Jun Xu1,2#, Guo-Liang Shen1,2✉

1. Department of Burn and Plastic Surgery , The First Affiliated Hospital of Soochow University, Suzhou, P.R. China, 215000.
2. Department of Surgery, Soochow University, Suzhou, P.R. China, 215000.
#These authors contributed equally to this work.

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Citation:
Han W, Xu J, Shen GL. Prognostic implication and functional annotations of APOBEC3G expression in patients with Melanoma. J Cancer 2020; 11(17):5245-5256. doi:10.7150/jca.46383. Available from https://www.jcancer.org/v11p5245.htm

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Abstract

Aim: Skin cutaneous melanoma (SKCM) is one of the most life-threatening malignancies damaging human health. APOBEC3G (A3G) has been found in several cancers; however, the role of A3G in SKCM is rarely studied. This study aimed to investigate the expression of A3G in tumor tissue and its prognostic value in SKCM patients.

Method: A total of 512 SKCM patients from the First Affiliated Hospital of Soochow University (FAHSU) and the Cancer Genome Atlas (TCGA) database were consecutively recruited in analyses. Differential transcriptional and proteome expression profiles were obtained from multiple datasets. GEPIA was used to assess the survival analysis between distinguished groups. Both univariate and multivariate Cox regression analysis was performed to address the influence of independent factors on disease-free survival (RFS) and overall survival (OS). In addition, 31 SKCM and 31 nevus tissues were collected for immunohistochemical (IHC) staining and evaluation. STRING, DAVID and Gene Set Enrichment Analysis (GSEA) was utilized to conduct a network of related genes and significant pathways. Furthermore, we investigated the relationship of A3G with tumor-infiltrating immune cells (TIICs) by TIMER and TISIDB.

Result: We found both transcriptional and proteomics expressions of A3G were elevated in SKCM. Survival analysis and ROC curves showed significant diagnostic and prognostic ability of A3G. IHC results showed increased expression of A3G in SKCM compared to nevus tissues. Importantly, A3G expression was closely associated with the immune-infiltrating levels of B cells, CD4+ T, CD8+ T, neutrophils, macrophages and dendritic cells.

Conclusion: In summary, our study first reveals that elevated A3G expression is significantly correlated with better prognosis in SKCM patients. The role of A3G in SKCM demonstrated that it might be a prognostic and immunotherapeutic biomarker for SKCM.

Keywords: APOBEC3G, melanoma, immune, prognosis