Clinical and Mechanistic Insights Into the Expression of Sp100 Family Proteins in Various Cancers: A Systematic Review Publisher Pubmed



Azami M ; Sadeghi F ; Mohammadi N ; Shayegh ZS ; Hassanzadeh A ; Heidarzadeh MJ ; Zarinkhat A ; Mohamadi Z
Source: BMC Cancer Published:2025

Abstract

Introduction: Cancer remains a leading global health burden, with projections estimating 35 million new cases by 2050. The Speckled Protein 100 (SP100) family, comprising SP100, SP110, SP140, and SP140L, has emerged as a critical player in cancer biology due to their roles in transcriptional regulation, chromatin modification, and immune signaling. While SP100 acts as a tumor suppressor in malignancies like breast cancer, SP110 and SP140 are implicated in promoting oral squamous cell carcinoma and glioma progression, respectively, and SP140L is linked to poor prognosis in pancreatic adenocarcinoma. Despite growing evidence of their dual oncogenic and tumor-suppressive functions across cancers, inconsistencies in expression patterns, regulatory mechanisms, and clinical implications persist. The current review of the SP100 family’s roles in cancer aims to clarify any direct future translational research to enhance cancer outcomes. Method: Following PRISMA guidance, a comprehensive search was conducted in several databases (PubMed, Scopus, Web of Science, and Google Scholar). After RAYYAN-assisted deduplication and screening, studies analyzing SP100, SP110, SP140, or SP140L alterations in human cancers (excluding cell lines studies) were included. Data on genetic/epigenetic changes, cancer types, and clinical outcomes were extracted, with quality assessed via standardized tools. Results: This systematic review analyzed 29 studies (2004–2024) to evaluate the dual roles of SP100 family proteins (SP100, SP110, SP140, SP140L) across 25 cancer types. SP100 exhibited context-dependent roles: high expression correlated with better prognosis in breast/lung cancers but poorer outcomes in glioma/PAAD, while low expression in LSCC was linked to tumorigenesis. SP110 overexpression was tied to poor prognosis in oral, lung, and renal cancers but was protective in DLBCL. SP140, the most studied member, showed divergent associations: high expression worsened outcomes in ccRCC, glioma, and gynecologic cancers but improved survival in AML, osteosarcoma, and melanoma. Genetic/epigenetic alterations (mutations, copy number loss, and methylation) influenced prognosis in hematologic and solid tumors. SP140L, the least explored, correlated with poor PAAD prognosis. Conclusion: This study highlights the dual oncogenic/tumor-suppressive roles of SP100 family proteins across cancers. It also introduces this family as a therapeutic target. Further, it underscores their prognostic value in hematologic and solid tumors, highlighting SP140 as a key biomarker and SP100/SP140 inhibitors as promising strategies. Geographic bias and limited SP140L data reveal gaps; Future research should include multi-center studies, standardized methods, and mechanistic exploration of SP140L and SP110 in the immune microenvironment. Prioritizing clinical trials targeting SP100 family members could advance precision oncology and immunotherapy integration. © 2025 Elsevier B.V., All rights reserved.