Metabolomic profiling identifies novel biomarkers and mechanisms in human bladder cancer treated with submucosal injection of gemcitabine

Yang,Chao; Sun,Xian; Wang,Hengbing; Lu,Ting; Wu,Keqing; Guan,Yusheng; Tang,Jing; Liang,Jian; Sun,Rongli; Guo,Zhongying; Zheng,Sinian; Wu,Xiaoli; Jiang,Hesong; Jiang,Xi; Zhong,Bing; Niu,Xiaobing; Sun,Suan; Wang,Xinru; Chen,Minjian; Fu,Guangbo

doi:10.3892/ijmm.2019.4347

Metabolomic profiling identifies novel biomarkers and mechanisms in human bladder cancer treated with submucosal injection of gemcitabine

Authors:
- Chao Yang
- Xian Sun
- Hengbing Wang
- Ting Lu
- Keqing Wu
- Yusheng Guan
- Jing Tang
- Jian Liang
- Rongli Sun
- Zhongying Guo
- Sinian Zheng
- Xiaoli Wu
- Hesong Jiang
- Xi Jiang
- Bing Zhong
- Xiaobing Niu
- Suan Sun
- Xinru Wang
- Minjian Chen
- Guangbo Fu
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Affiliations: Department of Urology, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China, State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China, Center of Reproduction and Genetic, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China, Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu 210009, P.R. China, Department of Pathology, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China, Department of Urology, Ningbo Medical Center Lihuili Eastern Hospital, Ningbo, Zhejiang 315040, P.R. China, Department of Pharmacy, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
Published online on: September 23, 2019 https://doi.org/10.3892/ijmm.2019.4347
Pages: 1952-1962
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Bladder cancer (BCa) is a common urinary tract malignancy with frequent recurrences after initial resection. Submucosal injection of gemcitabine prior to transurethral resection of bladder tumor (TURBT) may prevent recurrence of urothelial cancer. However, the underlying mechanism remains unknown. In the present study, ultra‑performance liquid chromatography Q‑Exactive mass spectrometry was used to profile tissue metabolites from 12 BCa patients. The 48 samples included pre‑ and post‑gemcitabine treatment BCa tissues, as well as adjacent normal tissues. Principal component analysis (PCA) revealed that the metabolic profiles of pre‑gemcitabine BCa tissues differed significantly from those of pre‑gemcitabine normal tissues. A total of 34 significantly altered metabolites were further analyzed. Pathway analysis using MetaboAnalyst identified three metabolic pathways closely associated with BCa, including glutathione, purine and thiamine metabolism, while glutathione metabolism was also identified by the enrichment analysis using MetaboAnalyst. In search of the possible targets of gemcitabine, metabolite profiles were compared between the pre‑gemcitabine normal and post‑gemcitabine BCa tissues. Among the 34 metabolites associated with BCa, the levels of bilirubin and retinal recovered in BCa tissues treated with gemcitabine. When comparing normal bladder tissues with and without gemcitabine treatment, among the 34 metabolites associated with BCa, it was observed that histamine change may be associated with the prevention of relapse, whereas thiamine change may be involved in possible side effects. Therefore, by employing a hypothesis‑free tissue‑based metabolomics study, the present study investigated the metabolic signatures of BCa and found that bilirubin and retinal may be involved in the mechanism underlying the biomolecular action of submucosal injection of gemcitabine in urothelial BCa.

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