Abstract: SA-PO0223
Effect of TMEM27 Expression on Metabolic Regulation in Clear Cell Renal Cell Carcinoma
Session Information
- Onconephrology: MGRS, HSCT, Electrolytes, RCC, and More
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1700 Onconephrology
Authors
- Grewal, Rickinder, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States
- Mills, Bradley N, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States
- Beane, Timothy Jason, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States
- Chen, Luojing, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States
- Rappold, Phillip, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States
- Le, Thu H., University of California Irvine School of Medicine, Irvine, California, United States
Background
Transmembrane protein 27 (TMEM27), or collectrin, a glycoprotein and homolog of angiotensin-converting enzyme-related carboxypeptidase 2 (ACE2), functions as a crucial regulator of amino acid (AA) uptake in the proximal tubule of the kidney. We previously reported that the absence of TMEM27 expression on clear cell renal cell carcinoma (ccRCC) cells correlates with more aggressive tumor characteristics and poorer all-cause mortality and disease-free survival. However, the mechanism underlying this association is unknown. We hypothesize that the loss of TMEM27 alters the metabolome of tumor cells through its effects on AA bioavailability in the tumor microenvironment.
Methods
The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma dataset was analyzed via the UCSC Xena tool. Cohorts containing the 50 highest and lowest TMEM27 expressing samples were analyzed via the Xena Differential Gene Expression Pipeline.
Results
Gene expression analysis revealed 6,498 genes that are differentially expressed between the two cohorts (Fig. 1; Red: up-regulated genes with logFC > 1.5; Blue: down-regulated genes with logFC < -1.5; p-value < 0.05). Pathway enrichment analysis shows several metabolic pathways are up-regulated in high TMEM27 expressing ccRCC, including AA metabolism, Nrf2, and mitochondrial fatty acid oxidation (Fig. 2).
Conclusion
Altered TMEM27 expression may impact AA availability, resulting in a metabolic shift that influences ccRCC cell growth. Further studies to characterize the metabolite profile and transcriptome of TMEM27 high/low ccRCC tumors are warranted to better understand the mechanisms driving aggressive ccRCC phenotype and potentially identify novel therapeutic targets.
Fig. 1: Volcano plot of differences in gene expression between high and low TMEM27 ccRCC
Fig. 2: Pathway enrichment analysis of high TMEM27 expressing ccRCC