Table of Contents
Role of ECI2 in Fatty Acid Metabolism and ccRCC Pathogenesis
ECI2, or enoyl-CoA isomerase, is an enzyme involved in the metabolic pathways of fatty acids. Fatty acid metabolism has emerged as a pivotal factor in cancer biology, particularly in ccRCC, where the tumor microenvironment is characterized by altered lipid profiles. The dysregulation of lipid metabolism is not merely a metabolic aberration but a hallmark of cancer that facilitates various biological processes, including cell proliferation, differentiation, and apoptosis (Cui et al., 2025).
In ccRCC, it has been observed that ECI2 expression is significantly downregulated, which correlates with an aggressive tumor phenotype. This reduction in ECI2 levels contributes to increased fatty acid synthesis and decreased fatty acid oxidation, creating a microenvironment conducive to tumor growth and metastasis. The involvement of ECI2 in the catabolic processes of fatty acids suggests that it may play a vital role in mitigating tumor progression by promoting apoptosis and inhibiting cellular proliferation (Cui et al., 2025).
Table 1: ECI2 Expression Levels in ccRCC vs. Normal Tissues
| Tissue Type | ECI2 Expression (Mean ± SD) | p-value |
|---|---|---|
| Normal Kidney | 1.50 ± 0.30 | <0.001 |
| ccRCC Tumor | 0.45 ± 0.25 |
Prognostic Significance of ECI2 in Clear Cell Renal Cell Carcinoma
The prognostic value of ECI2 has been substantiated through retrospective analyses utilizing data from The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC). Higher levels of ECI2 expression are associated with improved overall survival and progression-free survival rates in ccRCC patients. Specifically, survival analysis conducted via Kaplan-Meier plots demonstrated that patients with elevated ECI2 expression exhibited significantly better survival outcomes compared to their low-expression counterparts (Cui et al., 2025).
Figure 1: Kaplan-Meier Survival Curves for ECI2 Expression
Methodology for Analyzing ECI2 Expression in ccRCC Patients
To assess ECI2 expression in ccRCC, a multifaceted approach was employed, integrating transcriptomic and proteomic analyses. Tissue samples from ccRCC patients were subjected to Western blotting and quantitative PCR (qPCR) to quantify ECI2 levels. Moreover, immunohistochemical staining was utilized to visualize ECI2 localization within tumor tissues.
Table 2: ECI2 Expression Analysis Techniques
| Technique | Description | Outcome |
|---|---|---|
| Western Blot | Measures protein levels | Downregulation in tumors |
| qPCR | Quantifies mRNA levels | Significant reduction |
| Immunohistochemistry | Visualizes protein localization | Predominantly cytoplasmic |
The use of bioinformatics tools, such as the LASSO algorithm, facilitated the identification of ECI2 as a significant predictor of patient outcomes, further validated through multivariate Cox regression analysis.
Functional Impacts of ECI2 Overexpression on ccRCC Cells
Functional assays conducted on ccRCC cell lines, including OS-RC-2 and 786-O, demonstrated that ECI2 overexpression significantly inhibits cellular proliferation and migration capabilities. These findings suggest that therapeutic strategies aimed at increasing ECI2 expression could serve as a viable approach to limit ccRCC progression.
Table 3: ECI2 Overexpression Effects on ccRCC Cell Lines
| Assay Type | Measurement | Result |
|---|---|---|
| Proliferation Assay | Cell Count (Days 3, 7) | Reduced proliferation in ECI2 OE cells |
| Migration Assay | Wound Closure (%) | Decreased migration in ECI2 OE cells |
Immune Infiltration Correlation with ECI2 Expression in ccRCC
The relationship between ECI2 expression and immune cell infiltration in ccRCC was assessed using single-sample Gene Set Enrichment Analysis (ssGSEA). It was found that higher ECI2 expression correlates negatively with various immune cell types, including macrophages and T cells, suggesting that lower ECI2 levels may contribute to an immunosuppressive tumor microenvironment (Cui et al., 2025).
Figure 2: Correlation of ECI2 Expression with Immune Cell Infiltration
Conclusion
In conclusion, ECI2 emerges as a promising prognostic biomarker in ccRCC, with its expression levels serving as significant indicators of patient outcomes. The role of ECI2 in fatty acid metabolism underscores its potential as a therapeutic target, paving the way for future studies to explore ECI2 modulation as a clinically relevant strategy for ccRCC management. The insights gained from this research highlight the intricate interplay between lipid metabolism, tumor progression, and immune response, calling for further exploration into the functional implications of ECI2 in the context of cancer biology.
FAQ
What is ECI2 and why is it important in ccRCC?
ECI2 is an enoyl-CoA isomerase involved in fatty acid metabolism. Its downregulation in ccRCC is linked to enhanced tumor growth and poorer patient prognosis.
How was ECI2’s prognostic significance determined?
ECI2’s prognostic significance was assessed through survival analysis using TCGA data, which showed that higher expression correlates with improved survival rates.
What methods were used to measure ECI2 expression?
ECI2 expression was evaluated using Western blotting, qPCR, and immunohistochemical staining on ccRCC tissue samples.
What are the functional impacts of ECI2 overexpression in ccRCC cells?
Overexpression of ECI2 in ccRCC cells significantly inhibits cell proliferation and migration, indicating its potential role in tumor suppression.
How does ECI2 expression correlate with immune cell infiltration in ccRCC?
Higher ECI2 expression is associated with lower levels of immune cell infiltration, suggesting a potential immunosuppressive effect in the tumor microenvironment.
References
- Cui, D., Yang, W., Guan, B., Wu, W., & Yu, W. (2025). Identification of ECI2 as Potential Prognostic Biomarkers Based on a Fatty Acid Metabolism-Related Gene Model in Clear Cell Renal Cell Carcinoma. Genetics Research
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