High Membranous Expression of Fatty Acid Transport Protein 4 Is Associated with Tumorigenesis and Tumor Progression in Clear Cell Renal Cell Carcinoma

The increased requirement of fatty acids forces cancer cells to enhance uptake of fatty acids from the extracellular milieu, in addition to de novo lipogenesis. Coexpression of cluster of differentiation 36 (CD36) with fatty acid transport protein 4 (FATP4) or long-chain acyl CoA synthetase 1 (ACSL1...

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Published in:Disease markers 2019-01, Vol.2019 (2019), p.1-7
Main Authors: Choi, Jung-Woo, Oh, Hwa Eun, Lee, Ju-Han, Jeong, Hoiseon, Jung, Jiyoon, Kim, Young-Sik, Lee, Eung Seok
Format: Article
Language:English
Subjects:
Cancer
Carcinoma, Renal cell
CD36 antigen
Clear cell-type renal cell carcinoma
Cloning
Data analysis
Data processing
Development and progression
Fatty acids
Genomes
Hypoxia
Kidney cancer
Ligases
Lipids
Lipogenesis
Metabolism
Metastasis
Necrosis
Physiology
Protein transport
Proteins
Transport
Tumor cells
Tumorigenesis
Tumors
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Summary:The increased requirement of fatty acids forces cancer cells to enhance uptake of fatty acids from the extracellular milieu, in addition to de novo lipogenesis. Coexpression of cluster of differentiation 36 (CD36) with fatty acid transport protein 4 (FATP4) or long-chain acyl CoA synthetase 1 (ACSL1) synergistically activated fatty acid uptake in experimental models. In this study, we investigated the immunohistochemical expression of CD36, FATP4, and ACSL1 in 180 cases of clear cell renal cell carcinoma (RCC) in comparison with 80 specimens of the normal kidney. We also examined the clinical implication of these three fatty acid transporters in RCC, which was validated by an open-access The Cancer Genome Atlas data analysis. Both CD36 and FATP4 revealed higher membranous expressions in RCC tumor cells than in normal cells. In contrast, ACSL1 expression was remarkably reduced in RCC tumor cells compared to normal cells. CD36, FATP4, and ACSL1 showed high expressions in 74 (41.1%), 85 (47.2%), and 72 (40.0%) out of 180 RCC cases, respectively. Clinically, high FATP4 in tumor cells was associated with female gender (p=0.05), high TNM stage (p=0.039), tumor necrosis (p=0.009), and tumor recurrence (p=0.037), while high ACSL1 was only related to female gender (p=0.023). CD36 expression revealed no correlation with the clinicopathologic parameters of RCC. Increased FATP4 expression displayed an association with short recurrence-free survival (p=0.003). In conclusion, the high FATP4 expression was clinically associated with poor prognostic factors of RCC. Overexpression of membranous FATP4 and CD36 combined with reduced cytoplasmic expression of ACSL1 might be a tumor-specific feature of RCC, contributing to the tumorigenesis and tumor progression.
ISSN:0278-0240
1875-8630
DOI:10.1155/2019/5702026