Pan-cancer analysis of FBXW family with potential implications in prognosis and immune infiltration

Front Immunol. 2022 Dec 14:13:1084339. doi: 10.3389/fimmu.2022.1084339. eCollection 2022.

Abstract

Background: The F-box and WD repeat domain containing (FBXW) family of SCF E3 complexes has 10 members that are responsible for ubiquitination and degradation of substrate proteins involved in cell cycle regulation and tumorigenesis. Among them, FBXW1 (also called b-TrCP1/BTRC) and FBXW7 are the central proteins in this category. However, there is still a lack of elaborate exploration of the contribution of FBXW family members, especially FBXW1 and FBXW7, in various tumor types.

Methods: In this present study, we preliminarily analyzed the genetic structure characteristics of the FBXW family, and systematically investigated their expression patterns and clinical correlations based on the TCGA pan-cancer data. Survival analysis of FBXWs was also conducted through the Kaplan-Meier method. In addition, we assessed their immune infiltration level through immune-related algorithms like Timer and xCell.

Results: There were obvious genetic heterogeneity and different clinical traits in FBXW family members. Moreover, we found that FBXW family genes may be useful in predicting prognosis and therapeutic efficacy using survival analysis. In addition, the immune infiltration of FBXW family was also clearly illustrated in this study. The results showed these genes were closely involved in immune components such as immune score, immune subtypes, tumor-infiltrating lymphocytes and immune checkpoints. Notedly, FBXW1 as an oncogene and FBXW7 as a tumor suppressor gene also show opposite relationships on immune cells.

Conclusion: Our results provided valuable strategies to guide the therapeutic orientation concerning the role of FBXW family genes in cancer.

Keywords: FBXW family; immune infiltration; pan-cancer; prognosis; therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Checkpoints
  • F-Box Proteins* / genetics
  • F-Box Proteins* / immunology
  • F-Box-WD Repeat-Containing Protein 7 / genetics
  • F-Box-WD Repeat-Containing Protein 7 / immunology
  • Humans
  • Neoplasms* / genetics
  • Neoplasms* / immunology
  • Prognosis
  • Ubiquitination

Substances

  • F-Box-WD Repeat-Containing Protein 7
  • FBXW7 protein, human
  • BTRC protein, human
  • F-Box Proteins