J Cancer 2020; 11(6):1478-1485. doi:10.7150/jca.36438

Research Paper

Alteration of CYP4A11 expression in renal cell carcinoma: diagnostic and prognostic implications

Sup Kim1, Jin Man Kim2, Hyo Jin Lee3, Jae Sung Lim4, In-Ock Seong2, Kyung-Hee Kim2✉

1. Department of Radiation Oncology, Chungnam National University Hospital, Daejeon, South Korea;
2. Department of Pathology/Medical Science, Chungnam National University School of Medicine, Daejeon, South Korea;
3. Division of Hematology/Oncology, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, South Korea;
4. Department of Urology, Chungnam National University School of Medicine, Daejeon, South Korea.

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Citation:
Kim S, Kim JM, Lee HJ, Lim JS, Seong IO, Kim KH. Alteration of CYP4A11 expression in renal cell carcinoma: diagnostic and prognostic implications. J Cancer 2020; 11(6):1478-1485. doi:10.7150/jca.36438. Available from https://www.jcancer.org/v11p1478.htm

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Abstract

Background: Cytochrome P-450 4A11 (CYP4A11) and peroxisome proliferator-activated receptor-α (PPARα) are expressed at high levels in renal proximal tubules, and upregulation of CYP4A11 protein levels is known to be influenced by PPAR agonists. The goal of this study was to evaluate the clinicopathological role of CYP4A11 expression in renal cell carcinoma (RCC).

Methods: We performed immunohistochemical analysis of CYP4A11, CYP4A22 and PPARα and correlated the results with the clinicopathological features of RCC (n=139). Reverse transcription digital droplet polymerase chain reaction (RT-ddPCR) against CYP4A11 and CYP4A22 was also performed.

Results: CYP4A11 mRNA expression levels were higher in non-neoplastic kidney tissues than in matched tumor tissues in 12 matched pairs of freshly frozen primary clear-cell RCC (ccRCC) and nontumor tissue (p=0.002). Immunohistochemical staining showed that CYP4A11 expression was significantly lower in ccRCC than in non-ccRCCs, including papillary, chromophobe, and unclassified RCCs (p<0.001). CYP4A11 expression was associated with PPARα expression, males and high nuclear histologic grades (p=0.001, p=0.018 and p<0.001). Univariate and multivariate analyses revealed that CYP4A11 expression was correlated with short overall survival (p=0.007 and p=0.010).

Conclusion: These findings suggest that CYP4A11 expression is a potential poor prognostic factor of RCC. The considerable decrease in CYP4A11 expression is a predictive diagnostic factor of ccRCC, and CYP4A11 metabolism in ccRCC might be different from that in non-ccRCCs.

Keywords: cytochrome P450 CYP4A11, peroxisome proliferator-activated receptor-α, renal cell carcinoma.