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  3. Metabolic reprogramming based on RNA sequencing of gemcitabine-resistant cells reveals the FASN gene as a therapeutic for bladder cancer

Metabolic reprogramming based on RNA sequencing of gemcitabine-resistant cells reveals the FASN gene as a therapeutic for bladder cancer

  • J Transl Med. 2024 Jan 13;22(1):55. doi: 10.1186/s12967-024-04867-8.
Lijie Zhou # 1 2 3,  Kaixuan Du # 4 5 6,  Yiheng Dai # 4 5 6,  Youmiao Zeng 4 5 6,  Yongbo Luo 4 5,  Mengda Ren 4 5,  Wenbang Pan 4 5,  Yuanhao Liu 4 5,  Lailai Zhang 4 5,  Ronghui Zhu 4 5,  Dapeng Feng 4 5,  Fengyan Tian 7,  Chaohui Gu 8 9 10
Affiliations

Affiliations

  • 1 Department of Urology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. zhouxiaozhou29@126.com.
  • 2 Department of Urology, Henan Institute of Urology and Zhengzhou Key Laboratory for Molecular Biology of Urological Tumor Research, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. zhouxiaozhou29@126.com.
  • 3 Unit of Day Surgery Center, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. zhouxiaozhou29@126.com.
  • 4 Department of Urology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
  • 5 Department of Urology, Henan Institute of Urology and Zhengzhou Key Laboratory for Molecular Biology of Urological Tumor Research, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
  • 6 Unit of Day Surgery Center, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 7 Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. fccguzh@zzu.edu.cn.
  • 8 Department of Urology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. zgwhgch@hotmail.com.
  • 9 Department of Urology, Henan Institute of Urology and Zhengzhou Key Laboratory for Molecular Biology of Urological Tumor Research, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. zgwhgch@hotmail.com.
  • 10 Unit of Day Surgery Center, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. zgwhgch@hotmail.com.
  • # Contributed equally.
PMID: 38218866 DOI: 10.1186/s12967-024-04867-8
Abstract

Bladder Cancer (BLCA) is the most frequent malignant tumor of the genitourinary system. Postoperative chemotherapy drug perfusion and chemotherapy are important means for the treatment of BLCA. However, once drug resistance occurs, BLCA develops rapidly after recurrence. BLCA cells rely on unique metabolic rewriting to maintain their growth and proliferation. However, the relationship between the metabolic pattern changes and drug resistance in BLCA is unclear. At present, this problem lacks systematic research. In our research, we identified and analyzed resistance- and metabolism-related differentially expressed genes (RM-DEGs) based on RNA sequencing of a gemcitabine-resistant BLCA cell line and metabolic-related genes (MRGs). Then, we established a drug resistance- and metabolism-related model (RM-RM) through regression analysis to predict the overall survival of BLCA. We also confirmed that RM-RM had a significant correlation with tumor metabolism, gene mutations, tumor microenvironment, and adverse drug reactions. Patients with a high drug resistance- and metabolism-related risk score (RM-RS) showed more active lipid synthesis than those with a low RM-RS. Further in vitro and in vivo studies were implemented using Fatty Acid Synthase (FASN), a representative gene, which promotes gemcitabine resistance, and its inhibitor (TVB-3166) that can reverse this resistance effect.

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