ISG15

Overview

ISG15 encodes a ubiquitin-like protein that is robustly induced by type I interferons and plays roles in innate immune defense. In HGSOC, ISG15 is among the earliest upregulated IFN-stimulated genes in precursor lesions.

Alterations observed in the corpus

  • ISG15 is an IFN-stimulated gene upregulated early in HGSOC development beginning at the p53 signature stage; part of an IFN-alpha and IFN-gamma pathway gene upregulation program also including STAT1, IFITM1, IRF7, IRF9, TAP1, and HLA-A PMID:39386723.
  • ISG15 encodes an interferon-stimulated ubiquitin-like modifier that is targeted by UBA7 (a 3p-encoded E1 ubiquitin enzyme); UBA7 is up-regulated greater-than 2-fold in early-passage cells with engineered chromosome 3p deletion, consistent with IFN-pathway up-regulation observed by GSEA after 3p loss. PMID:29622463

Cancer types (linked)

  • HGSOC — upregulated in fallopian tube precursor lesions (p53 signatures, STICs) and invasive cancer; studied by GeoMx spatial transcriptomics on 44 specimens from 43 individuals PMID:39386723.

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • Early IFN pathway activation including ISG15 in HGSOC precursors could serve as a biomarker panel for risk stratification of high-risk patients PMID:39386723.

Open questions

  • Whether ISG15 has a direct functional role (e.g., via ISGylation of target proteins) in shaping the HGSOC immune microenvironment is unresolved PMID:39386723.

Sources

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