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Single-Cell and Integrative Analyses Uncover Therapeutic Potential of RFX1-Mediated Cuproptosis in PitNETs.
Shuangjian Yang1, Changqin Pu1, Congcong Deng1
1Department of Neurosurgery, China Pituitary Disease Registry Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 100730 Beijing, China.
Journal of Integrative Neuroscience
|May 30, 2026
Summary
This study reveals that copper-induced cell death (cuproptosis) is crucial in pituitary neuroendocrine tumors (PitNETs). The gene RFX1 suppresses tumor growth and offers a potential new therapeutic target for PitNETs.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Pituitary neuroendocrine tumors (PitNETs) exhibit diverse cellular compositions and growth patterns, with underlying mechanisms poorly understood.
- Cuproptosis, a copper-dependent cell death pathway, is implicated in various cancers but its role in PitNETs remains unexplored.
Purpose of the Study:
- To investigate the role and mechanisms of cuproptosis in the progression of PitNETs.
- To identify key regulators of cuproptosis and their impact on tumor invasiveness and growth.
Main Methods:
- Utilized bulk and single-cell sequencing, machine learning, Weighted Gene Co-expression Network Analysis (WGCNA), and random forest algorithms.
- Performed laboratory validation of identified key genes and pathways.
Main Results:
- Discovered significant differences in cuproptosis-related gene expression and immune profiles between invasive and non-invasive PitNETs.
- Developed a predictive model for tumor invasiveness based on cuproptosis-related genes, identifying distinct molecular subtypes.
- Identified and validated Regulatory Factor X1 (RFX1) as a crucial suppressor of PitNET growth that enhances sensitivity to cuproptosis.
Conclusions:
- Established a single-cell-level molecular understanding of PitNETs, highlighting RFX1-mediated cuproptosis as a key mechanism inhibiting tumor progression.
- RFX1 emerges as a promising therapeutic target for managing PitNETs, offering new avenues for treatment.
