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Published on: May 1, 2020
Prognostic role of eIF2α protein in metastatic renal cell cancer patients
Ferhat Ekinci1, Hanife Seda Mavili2, Nalan Neşe3
1Faculty of Medicine, Department of Medical Oncology, Celal Bayar University, Uncubozköy Street, Manisa, Turkey. drferhatekinci@hotmail.com.
Background:
One of the major dilemmas in the treatment of renal cell carcinoma (RCC) is the resistance to therapy that leads to a state of unresponsiveness, which is observed after a certain period. Among the potential causes of this, the impact of autophagy activation and the resulting endoplasmic reticulum (ER) stress due to the accumulation of misfolded or unfolded proteins has not been previously investigated.
Methods:
Patients treated in medical oncology clinics of a total of 3 centers between January 2011 and May 2022 were included. In the pathology preparations of a total of 83 patients diagnosed with metastatic RCC, we examined the effects of autophagy activation induced by mTOR inhibition through the analysis of LC3 and Beclin1 molecules, the differentiation from classical apoptosis pathways with the Bcl-2 level, the hypoxic condition with the HIF-1α level, and ER stress with the eukaryotic initiation factor 2α (eIF2α) level.
Results:
İn our study, found no significant effects of LC3 (p = 0.298), Beclin1 (p = 0.287), Bcl-2 (p = 0.435), and HIF-1α (p = 0.179) levels on either progression-free survival or overall survival. However, eIF2α (p = 0.017) was found to be a significantly decisive factor.
Conclusion:
Based on these results, we suggest that eIF2α may serve as a novel biomarker to predict survival and treatment response in metastatic RCC patients.
Insights
Therapy resistance in metastatic renal cell carcinoma (RCC) is a challenge. Endoplasmic reticulum (ER) stress, indicated by eIF2α levels, may predict patient survival and treatment response.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Metastatic renal cell carcinoma (RCC) presents treatment resistance challenges.
- Autophagy activation and endoplasmic reticulum (ER) stress are potential contributors to RCC resistance.
- The role of ER stress in RCC therapy resistance has not been previously explored.
Purpose of the Study:
- To investigate the impact of autophagy activation and ER stress on treatment resistance in metastatic RCC.
- To analyze specific molecular markers associated with autophagy, apoptosis, hypoxia, and ER stress.
Main Methods:
- Analysis of pathology preparations from 83 metastatic RCC patients.
- Examination of autophagy markers (LC3, Beclin1), apoptosis marker (Bcl-2), hypoxia marker (HIF-1α), and ER stress marker (eIF2α).
- Correlation of marker levels with progression-free and overall survival.
Main Results:
- No significant correlation was found between LC3, Beclin1, Bcl-2, or HIF-1α levels and patient survival.
- Elevated eukaryotic initiation factor 2α (eIF2α) levels were significantly associated with patient survival.
- eIF2α emerged as a decisive factor in predicting outcomes for metastatic RCC patients.
Conclusions:
- Eukaryotic initiation factor 2α (eIF2α) may serve as a novel biomarker for predicting survival in metastatic RCC.
- eIF2α levels could potentially predict treatment response in patients with metastatic RCC.
- Targeting ER stress pathways may offer new therapeutic strategies for overcoming RCC resistance.
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