Prognostic Significance of CHIP and RIPK3 in Non-Small Cell Lung Cancer
Jisup Kim1, Joon-Yong Chung2, Young Soo Park1
1Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
Abstract:
RIPK3 is a key regulator of necroptosis, which plays a double-edged sword role in tumor progression. CHIP is an E3 ubiquitin ligase that regulates necroptosis by degrading RIPK3. Here, we investigated the prognostic value of RIPK3 and CHIP expression in 404 patients with non-small cell lung cancer (NSCLC). Expressions of CHIP and RIPK3 showed opposite correlations with survival. CHIP expression was associated with the longer overall survival (OS), whereas RIPK3 expression was associated with the shorter OS. RIPK3 positivity showed marginal association with shorter OS and disease-free survival (DFS) in adjuvant radiotherapy recipients but not in non-recipients, suggesting that necroptosis may induce radioresistance. In multivariate analysis, CHIP expression was associated with longer OS. Compared with other patients, CHIP(-)/RIPK3(+) patients had shorter OS and DFS. In summary, in patients with NSCLC, the expression of CHIP was an independent favorable prognostic factor while that of RIPK3 was an adverse prognostic factor.
Insights
In non-small cell lung cancer (NSCLC), higher expression of CHIP correlates with longer survival, while higher RIPK3 expression is linked to shorter survival. These findings suggest CHIP and RIPK3 have opposing prognostic values in NSCLC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Necroptosis, regulated by RIPK3, has a complex role in tumor progression.
- CHIP, an E3 ubiquitin ligase, modulates necroptosis by targeting RIPK3 for degradation.
Purpose of the Study:
- To investigate the prognostic significance of Receptor-Interacting Protein Kinase 3 (RIPK3) and Carboxyl Terminus of Hsp70-Interacting Protein (CHIP) expression in non-small cell lung cancer (NSCLC).
Main Methods:
- Analysis of RIPK3 and CHIP expression levels in 404 NSCLC patients.
- Correlation of expression levels with overall survival (OS) and disease-free survival (DFS).
- Multivariate analysis to determine independent prognostic factors.
Main Results:
- CHIP expression was positively correlated with longer OS, while RIPK3 expression was associated with shorter OS.
- RIPK3 positivity suggested potential radioresistance in NSCLC patients receiving adjuvant radiotherapy.
- CHIP expression emerged as an independent favorable prognostic factor in multivariate analysis.
Conclusions:
- CHIP expression is a favorable prognostic indicator in NSCLC.
- RIPK3 expression is an adverse prognostic indicator in NSCLC.
- The opposing roles of CHIP and RIPK3 highlight their significance in NSCLC prognosis and potential therapeutic targeting.
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