A Novel Oncogenic Role of Disulfidptosis-related Gene SLC7A11 in Anti--tumor Immunotherapy Response to Human Cancers

Curr Cancer Drug Targets. 2024 Jan 31. doi: 10.2174/0115680096277818231229105732. Online ahead of print.

Abstract

Background: The protein Solute Carrier Family 7 Member 11 (SLC7A11) plays a pivotal role in cellular redox homeostasis by suppressing disulfidptosis, which restricts tumor growth. Yet, its relevance in prognosis, immunity, and cancer treatment efficacy is not well understood.

Methods: We conducted a comprehensive analysis of the expression of SLC7A11 across 33 cancer types, employing datasets from public databases. Methods, such as Cox regression and survival analyses assessed its prognostic significance, while functional enrichment explored the biological processes tied to SLC7A11. The association between SLC7A11 expression, immune cell infiltration, and immune-related gene expression was also scrutinized.

Results: Notably, SLC7A11 expression was more pronounced in cancerous compared to normal samples and correlated with higher tumor grades. Increased SLC7A11 expression was linked to poor outcomes, particularly in liver hepatocellular carcinoma (LIHC). This protein's expression also showcased significant relationships with diverse molecular and immune subtypes. Additionally, a prognostic nomogram was devised, integrating SLC7A11 expression and clinical variables. High SLC7A11 levels corresponded with cell growth and senescence pathways in various cancers and with lipid and cholesterol metabolism in LIHC. Furthermore, potential therapeutic compounds for LIHC with high SLC7A11 were identified. Real-time PCR (qPCR) and Western blot were conducted to explore the expression of SLC7A11 in tumor tissues and cancer cell lines.

Conclusion: In summation, this study emphasizes the prognostic and immunological importance of SLC7A11, spotlighting its potential as a therapeutic target in LIHC.

Keywords: Solute carrier family 7 member 11; cancer therapy.; hepatocellular carcinoma; pan-cancer; prognostic biomarker; tumor microenvironment.