FANCI serve as a prognostic biomarker correlated with immune infiltrates in skin cutaneous melanoma

Front Immunol. 2023 Nov 22:14:1295831. doi: 10.3389/fimmu.2023.1295831. eCollection 2023.

Abstract

Background: As a member of tumor, Skin cutaneous melanoma (SKCM) poses a serious threat to people's health because of its strong malignancy. Unfortunately, effective treatment methods for SKCM remain lacking. FANCI plays a vital role in the occurrence and metastasis of various tumor types. However, its regulatory role in SKCM is unclear. The purpose of this study was to explore the association of FANCI with SKCM.

Methods: This study investigated the expression of FANCI in GSE46517, GSE15605, and GSE114445 from the Gene Expression Omnibus database and The Cancer Genome Atlas (TCGA)-SKCM datasets using the package "limma" or "DESeq2" in R environment and also investigated the prognostic significance of FANCI by utilizing the GEPIA database. Additionally, our research made use of real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical (IHC) staining to verify FANCI expression between SKCM and normal tissues and developed the knockdown of FANCI in A375 and A875 cells to further analyze the function of FANCI. Finally, this study analyzed the correlation of FANCI and tumor-infiltrating immune cells by CIBERSORT, ESTIMATE, and ssGSEA algorithms.

Results: The FANCI level was increasing in SKCM tissues from GSE46517, GSE15605, GSE114445, and TCGA-SKCM. However, high FANCI expression correlated with poor overall survival. The RT-qPCR and IHC confirmed the accuracy of bioinformatics. Knocking down FANCI suppresses A375 and A875 cell proliferation, migration, and invasion. FANCI could be involved in the immunological milieu of SKCM by regulating immune responses and infiltrating numerous immune cells, particularly neutrophils, CD8+ T cells, and B cells. Furthermore, patients with SKCM who have a high FANCI expression level are reported to exhibit immunosuppression, whereas those with a low FANCI expression level are more likely to experience positive outcomes from immunotherapy.

Conclusions: The increased FANCI expression in SKCM can be a prognostic biomarker. Knockdown FANCI can reduce the occurrence and progression of SKCM. The FANCI expression provides a foundation for predicting the immune status and treatment of SKCM.

Keywords: FANCI; immune infiltrates; immunotherapy; prognostic biomarker; skin cutaneous melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Fanconi Anemia Complementation Group Proteins
  • Humans
  • Melanoma* / genetics
  • Prognosis
  • Skin Neoplasms* / genetics

Substances

  • Biomarkers
  • FANCI protein, human
  • Fanconi Anemia Complementation Group Proteins

Supplementary concepts

  • Fanconi Anemia, Complementation Group I

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The whole program obtained sponsorship from National Natural Science Foundation of the People’s Republic of China (82004366), Natural Science Foundation of Shanghai (YKHHFX01190408), Training Program for High-caliber Talents of Clinical Research at Affiliated Hospitals of SHUTCM (NO. 2023LCRC09), Shanghai Municipal Commission of science and technology, Sailing Program (NO. 22YF1449500), and Special Clinical Research Special Project of Shanghai Municipal Health Commission (20234Y0163).