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Research Paper|Volume 11, Issue 16|pp 6503—6521

Procollagen-lysine, 2-oxoglutarate 5-dioxygenases 1, 2, and 3 are potential prognostic indicators in patients with clear cell renal cell carcinoma

Wen-Hao Xu1,2, Yue Xu3, Jun Wang1,2, Xi Tian1,2, Junlong Wu1,2, Fang-Ning Wan1,2, Hong-Kai Wang1,2, Yuan-Yuan Qu1,2, Hai-Liang Zhang1,2, Ding-Wei Ye1,2
  • 1Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China
  • 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
  • 3Department of Ophthalmology, The First Affiliated Hospital of Soochow University, Suzhou 215000, P.R. China
* Equal contribution
Received: April 26, 2019Accepted: August 14, 2019Published: August 25, 2019
https://doi.org/10.18632/aging.102206

Copyright © 2019 Xu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Intratumoral fibrosis is a frequent histologic finding in highly vascularized clear cell renal cell carcinoma (ccRCC). Here, we investigated the expression of a family of collagen-modifying enzymes, procollagen-lysine, 2-oxoglutarate 5-dioxygenases 1, 2, and 3 (PLOD1/2/3), in ccRCC tissues and assessed the prognostic value of wild-type and genetically mutated PLOD1/2/3 for ccRCC patients. Normal kidney and ccRCC mRNA and protein expression datasets were obtained from Oncomine, The Cancer Genome Atlas, and Human Protein Atlas databases. Associations between PLOD1/2/3 expression, clinicopathological variables, and patient survival were evaluated using Cox regression and Kaplan–Meier analyses. PLOD1/2/3 mRNA and protein expression levels were significantly elevated in ccRCC tissues compared with normal kidney. Increased PLOD1/2/3 mRNA expression was significantly associated with advanced tumor stage, high pathological grade, and shorter progression-free and overall survival (all p<0.01). Genetic mutation of PLOD1/2/3 was present in ~3% of ccRCC patients and was associated with significantly poorer prognosis compared with expression of wild-type PLOD1/2/3 (p<0.001). This study thus identifies tumor expression of wild-type or mutated PLOD1/2/3 mRNA as a potential predictive biomarker for ccRCC patients and sheds light on the underlying molecular pathogenesis of ccRCC.