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Peer-reviewedCC BYCancer Cell International

Bioinformatics analysis of PFKFB family in pan-cancer and preliminary exploration of PFKFB4 in bladder cancer

6 affiliations
  1. 1Huazhong University of Science and Technology
  2. 2School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology
  3. 3Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine
  4. 4Department of Otolaryngology, The first Hospital of China Medical University
  5. 5Department of Medical Oncology, Rui’an People’s Hospital, The Third Affiliated Hospital of Wenzhou Medical University
  6. 6Gastrointestinal surgery, Wuhan Union Hospital

Abstract

Background The phosphofructokinase-fructose bisphosphatases (PFKFBs) family is critical in tumors and the immune system. Nevertheless, the involvement of the PFKFB family genes in the immune microenvironment and prognosis of tumor patients has not been investigated using genomic and transcriptomic analyses. Methods We collected data from 33 cancers and comprehensively analyzed the PFKFB family genes for abnormal expression, genomic alterations, diagnostic and prognostic roles, subcellular localization, pathway enrichment, immune microenvironment, association with immune checkpoints, and drug sensitivity in the disease, as well as predicting patients’ immunotherapeutic response to ICI and targeting of small molecule drugs, and performed the above results by immunohistochemical staining, pathological sections, and experiments for validation. Finally, we experimentally confirmed the role of PFKFB4 in bladder cancer. Results We found the differential expression and diagnostic biomarker value of PFKFBs family members in pan-cancer, and also found that they play a key role in pan-cancer in relation to the tumor microenvironment. PFKFBs are closely associated with common immune checkpoints, TMB and MSI, and PFKFBs family members can predict immunotherapy response in patients with a wide range of cancers. Finally, it was experimentally determined that knockdown of PFKFB4 gene expression inhibited proliferation and invasion of bladder cancer cells. Conclusions Our study highlights the great potential of PFKFBs as prognostic and immunotherapeutic response biomarkers, which may pave the way for further investigation of the tumor infiltration mechanism and therapeutic potential of PFKFBs in cancer.

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BibTeX
@article{xu2026bioinformatics,
  title = {{Bioinformatics analysis of PFKFB family in pan-cancer and preliminary exploration of PFKFB4 in bladder cancer}},
  author = {Yan Xu and Jian Xu and Chunyang Han and Qianlong Li and Hualong Lin and Zhiyong Wang},
  journal = {Cancer Cell International},
  year = {2026},
  month = jul,
  doi = {10.1186/s12935-026-04354-8},
  url = {https://doi.org/10.1186/s12935-026-04354-8},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Bioinformatics analysis of PFKFB family in pan-cancer and preliminary exploration of PFKFB4 in bladder cancer
AU  - Yan Xu
AU  - Jian Xu
AU  - Chunyang Han
AU  - Qianlong Li
AU  - Hualong Lin
AU  - Zhiyong Wang
PY  - 2026
DA  - 2026/07/01
JO  - Cancer Cell International
DO  - 10.1186/s12935-026-04354-8
UR  - https://doi.org/10.1186/s12935-026-04354-8
AB  - Background The phosphofructokinase-fructose bisphosphatases (PFKFBs) family is critical in tumors and the immune system. Nevertheless, the involvement of the PFKFB family genes in the immune microenvironment and prognosis of tumor patients has not been investigated using genomic and transcriptomic analyses. Methods We collected data from 33 cancers and comprehensively analyzed the PFKFB family genes for abnormal expression, genomic alterations, diagnostic and prognostic roles, subcellular localization, pathway enrichment, immune microenvironment, association with immune checkpoints, and drug sensitivity in the disease, as well as predicting patients’ immunotherapeutic response to ICI and targeting of small molecule drugs, and performed the above results by immunohistochemical staining, pathological sections, and experiments for validation. Finally, we experimentally confirmed the role of PFKFB4 in bladder cancer. Results We found the differential expression and diagnostic biomarker value of PFKFBs family members in pan-cancer, and also found that they play a key role in pan-cancer in relation to the tumor microenvironment. PFKFBs are closely associated with common immune checkpoints, TMB and MSI, and PFKFBs family members can predict immunotherapy response in patients with a wide range of cancers. Finally, it was experimentally determined that knockdown of PFKFB4 gene expression inhibited proliferation and invasion of bladder cancer cells. Conclusions Our study highlights the great potential of PFKFBs as prognostic and immunotherapeutic response biomarkers, which may pave the way for further investigation of the tumor infiltration mechanism and therapeutic potential of PFKFBs in cancer.
SN  - 1475-2867
ER  -