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Fatty acid metabolism-related molecular subtypes and a novel model for predicting prognosis in bladder cancer patients

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Abstract

This study aims to develop fatty acid metabolism-related molecular subtypes and construct a fatty acid metabolism-related novel model for bladder cancer (BCa) by bioinformatic profiling. Genome RNA-seq expression data of BCa samples from the TCGA database and GEO database were downloaded. We then conducted consensus clustering analysis to identify fatty acid metabolism-related molecular subtypes for BCa. Univariate and multivariate Cox regression analysis were performed to identify a novel prognostic fatty acid metabolism-related prognostic model for BCa. Finally, we identified a total of three fatty acid metabolism-related molecular subtypes for BCa. These three molecular subtypes have significantly different clinical characteristics, PD-L1 expression levels, and tumor microenvironments. Also, we developed a novel fatty acid metabolism-related prognostic model. Patients with low-risk score have significantly preferable overall survival compared with those with high-risk score in the training, testing, and validating cohorts. The area under the ROC curve (AUC) for overall survival prediction was 0.746, 0.681, and 0.680 in the training, testing and validating cohorts, respectively. This model was mainly suitable for male, older, high-grade, cluster 2–3, any TCGA stage, any N-stage, and any T-stage patients. Besides, we selected FASN as a hub gene for BCa and further qRT-PCR validation was successfully conducted. In conclusion, we developed and successfully validated a novel fatty acid metabolism-related prognostic model for predicting outcome for BCa patients.

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Availability of data and materials

All data generated or analyzed during the present study was downloaded from TCGA database (https://portal.gdc.cancer.gov), GEO database (https://www.ncbi.nlm.nih.gov), and Molecular Signatures Database (MSigDB) (https://www.gsea-msigdb.org/gsea/msigdb).

References

  • Abdelrahman AE, Rashed HE, Elkady E, et al. 2019 Fatty acid synthase, Her2/neu, and E2F1 as prognostic markers of progression in non-muscle invasive bladder cancer. Ann. Diagn. Pathol. 39 42–52

    Article  PubMed  Google Scholar 

  • Ben Fradj MK, Ouanes Y, Hadj-Taieb S, et al. 2018 Decreased oleic acid and marine n – 3 polyunsaturated fatty acids in Tunisian patients with urothelial bladder cancer. Nutr. Cancer 70 1043–1050

    Article  PubMed  CAS  Google Scholar 

  • Bhanvadia SK 2018 Bladder cancer survivorship. Curr. Urol. Rep. 19 111

    Article  PubMed  Google Scholar 

  • Bladder cancer: diagnosis and management of bladder cancer: © NICE 2015 Bladder cancer: diagnosis and management of bladder cancer 2017. BJU Int. 120 755–765

    Google Scholar 

  • Chen JW, Dodia C, Feinstein SI, Jain MK, et al. 2000 1-Cys peroxiredoxin, a bifunctional enzyme with glutathione peroxidase and phospholipase A2 activities. J. Biol. Chem. 275 28421–28427

    Article  PubMed  CAS  Google Scholar 

  • Chowdhury PS, Chamoto K, Kumar A, et al. 2018 PPAR-induced fatty acid oxidation in t cells increases the number of tumor-reactive CD8 (+) T cells and facilitates anti-PD-1 therapy. Cancer Immunol. Res. 6 1375–1387

    Article  PubMed  CAS  Google Scholar 

  • Currie E, Schulze A, Zechner R, et al. 2013 Cellular fatty acid metabolism and cancer. Cell Metab. 18 153–161

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Czimmerer Z, Varga T, Poliska S, et al. 2012 Identification of novel markers of alternative activation and potential endogenous PPARγ ligand production mechanisms in human IL-4 stimulated differentiating macrophages. Immunobiology 217 1301–1314

    Article  PubMed  CAS  Google Scholar 

  • Dobruch J, Daneshmand S, Fisch M, et al. 2016 Gender and bladder cancer: a collaborative review of etiology, biology, and outcomes. Eur. Urol. 69 300–310

    Article  PubMed  Google Scholar 

  • Gao L, Meng J, Yue C, et al. 2021 Integrative analysis the characterization of peroxiredoxins in pan-cancer. Cancer Cell Int. 21 366

    Article  PubMed  PubMed Central  Google Scholar 

  • Goller L, Bergstrom M, Nilsson S, et al. 1995 Mao-a enzyme binding in bladder-cancer characterized with [C-11] harmine in frozen-section autoradiography. Oncol. Rep. 2 717–721

    PubMed  CAS  Google Scholar 

  • Jeong H, Oh HE, Kim H, et al. 2021 Upregulation of fatty acid transporters is associated with tumor progression in non-muscle-invasive bladder cancer. Pathol. Oncol. Res. 27 594705

    Article  PubMed  PubMed Central  Google Scholar 

  • Jiang F, Luo F, Zeng N, et al. 2022 Characterization of fatty acid metabolism-related genes landscape for predicting prognosis and aiding immunotherapy in glioma patients. Front. Immunol. 13 902143

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Joseph A, Juncheng P, Mondini M, et al. 2021 Metabolic features of cancer cells impact immunosurveillance. J. Immunother. Cancer 9 e002362

    Article  PubMed  PubMed Central  Google Scholar 

  • Ke ZB, Wu YP, Huang P, et al. 2020 Identification of novel genes in testicular cancer microenvironment based on ESTIMATE algorithm-derived immune scores. J. Cell Physiol. 236 706–713

    Article  PubMed  Google Scholar 

  • Lenis AT, Lec PM, Chamie K, et al. 2020 Bladder cancer: A review. JAMA 324 1980–1991

    Article  PubMed  CAS  Google Scholar 

  • Liberti MV and Locasale JW 2016 The Warburg effect: how does it benefit cancer cells? Trends Biochem Sci. 41 211–218

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Luo Y, Wang H, Liu B, et al. 2022 Fatty acid metabolism and cancer immunotherapy. Curr. Oncol. Rep. 24 659–670

    Article  PubMed  CAS  Google Scholar 

  • Mancini R, Noto A, Pisanu ME, et al. 2018 Metabolic features of cancer stem cells: the emerging role of lipid metabolism. Oncogene 37 2367–2378

    Article  PubMed  CAS  Google Scholar 

  • Martinez Rodriguez RH, Buisan Rueda O and Ibarz L 2017 Bladder cancer: Present and future. Med. Clin. 149 449–455

    Article  Google Scholar 

  • McConkey DJ and Choi W 2018 Molecular subtypes of bladder cancer. Curr. Oncol. Rep. 20 77

    Article  PubMed  Google Scholar 

  • Mou Z, Yang C, Zhang Z, et al. 2020 Transcriptomic analysis of glycolysis-related genes reveals an independent signature of bladder carcinoma. Front. Genet. 11 566918

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Scheiter A, Evert K, Reibenspies L, et al. 2022 RASSF1A independence and early galectin-1 upregulation in PIK3CA-induced hepatocarcinogenesis: new therapeutic venues. Mol. Oncol. 16 1091–1118

    Article  PubMed  CAS  Google Scholar 

  • Su YL, Luo HL, Huang CC, et al. 2020 Galectin-1 overexpression activates the FAK/PI3K/AKT/mTOR pathway and is correlated with upper urinary urothelial carcinoma progression and survival. Cells 9 806

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tao T, Su Q, Xu S, et al. 2019 Down-regulation of PKM2 decreases FASN expression in bladder cancer cells through AKT/mTOR/SREBP-1c axis. J. Cell Physiol. 234 3088–3104

    Article  PubMed  CAS  Google Scholar 

  • Vantaku V, Dong J, Ambati CR, et al. 2019 Multi-omics integration analysis robustly predicts high-grade patient survival and identifies CPT1B effect on fatty acid metabolism in bladder cancer. Clin. Cancer Res. 25 3689–3701

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vasekar M, Degraff D and Joshi M 2016 Immunotherapy in bladder cancer. Curr. Mol. Pharmacol. 9 242–251

    Article  PubMed  CAS  Google Scholar 

  • Warrick JI, Al-Ahmadie H, Berman DM, et al. 2023 International Society of Urological Pathology Consensus Conference on Current Issues in Bladder Cancer. Working Group 4: Molecular Subtypes of Bladder Cancer-Principles of Classification and Emerging Clinical Utility. Am. J. Surg. Pathol. 10-1097

  • Xiong Q, Feng D, Wang Z, et al. 2022 Fatty acid synthase is the key regulator of fatty acid metabolism and is related to immunotherapy in bladder cancer. Front. Immunol. 13 836939

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Xu N, Ke ZB, Lin XD, et al. 2020 Development and validation of a molecular prognostic index of bladder cancer based on immunogenomic landscape analysis. Cancer Cell Int. 20 302

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Anesthesiology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China

    Wen-Ting Su

  2. Department of Urology, Urology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China

    Jia-Yin Chen, Jiang-Bo Sun, Qi Huang, Zhi-Bin Ke, Shao-Hao Chen, Yun-Zhi Lin, Xue-Yi Xue, Yong Wei & Ning Xu

  3. Department of Urology, National Region Medical Centre, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China

    Jia-Yin Chen, Jiang-Bo Sun, Qi Huang, Zhi-Bin Ke, Shao-Hao Chen, Yun-Zhi Lin, Xue-Yi Xue, Yong Wei & Ning Xu

  4. Fujian Key Laboratory of Precision Medicine for Cancer, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China

    Xue-Yi Xue & Ning Xu

Authors
  1. Wen-Ting Su
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  2. Jia-Yin Chen
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  3. Jiang-Bo Sun
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  4. Qi Huang
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  5. Zhi-Bin Ke
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  6. Shao-Hao Chen
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  7. Yun-Zhi Lin
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  8. Xue-Yi Xue
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  9. Yong Wei
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  10. Ning Xu
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Contributions

Writing – original draft, W-T S. Writing – review and editing, YW, NX. Methodology, QH, J-B S, J-Y C. Investigation, Z-B K, S-H C. Formal analysis, Y-Z L, X-Y X. Data curation, QH, J-B S. Conceptualization, Z-B K, S-H C. Visualization, Y-Z L, X-Y X. Supervision, YW, NX, X-Y X. Project administration, W-T S, S-H C.

Corresponding authors

Correspondence to Yong Wei or Ning Xu.

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Conflict of interests

All authors declare no conflict of interests.

Additional information

Corresponding editor: Ram Rajasekharan

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Su, WT., Chen, JY., Sun, JB. et al. Fatty acid metabolism-related molecular subtypes and a novel model for predicting prognosis in bladder cancer patients. J Biosci 49, 11 (2024). https://doi.org/10.1007/s12038-023-00383-x

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