Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

Scientific Reports
  • View all journals
  • Search
  • My Account Login
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. scientific reports
  3. articles
  4. article
Pan-cancer analysis reveals the oncogenic and immunomodulatory roles of PTGFRN across human cancers
Download PDF
Download PDF
  • Article
  • Open access
  • Published: 27 February 2026

Pan-cancer analysis reveals the oncogenic and immunomodulatory roles of PTGFRN across human cancers

  • Nan Mu1 na1,
  • Tianjian Dong5 na1,
  • Qingyu Sheng2,
  • Zhuoning Duan3,
  • Xiangming Wang4 &
  • …
  • Qi Zhao2 

Scientific Reports , Article number:  (2026) Cite this article

  • 1213 Accesses

  • Metrics details

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Biomarkers
  • Cancer
  • Computational biology and bioinformatics
  • Immunology
  • Oncology

Abstract

The role of the prostaglandin F2 receptor negative regulator (PTGFRN) in tumor biology remains incompletely understood. This study aimed to perform a comprehensive pan-cancer analysis to elucidate the functions of PTGFRN in tumor progression and its potential immunomodulatory effects. Utilizing data from the cancer genome atlas (TCGA) and the genotype-tissue expression (GTEx) project, we analyzed PTGFRN expression profiles, genetic alterations (including mutations, copy number variations, and DNA methylation), and its prognostic significance across multiple cancer types. Pathway enrichment analysis was conducted using the R package “clusterProfiler.” The correlation between PTGFRN expression and immune cell infiltration levels within the tumor microenvironment was assessed via the TIMER2 database. PTGFRN was significantly overexpressed in a wide range of cancers, and its elevated expression was consistently associated with poorer patient prognosis. Furthermore, pan-cancer analysis revealed that PTGFRN expression is linked to an immunosuppressive tumor microenvironment, showing a positive correlation with immunosuppressive cells such as cancer-associated fibroblasts and a negative correlation with anti-tumor effector cells like CD8⁺ T cells. Functional validation in lung adenocarcinoma (LUAD) cells confirmed that PTGFRN acts as an oncogene, enhancing proliferative, migratory, and invasive capabilities. Our findings establish PTGFRN as a potential prognostic biomarker across cancer types. Its overexpression is indicative of an immunosuppressive tumor microenvironment, positioning PTGFRN as a promising therapeutic target for cancer immunotherapy.

Similar content being viewed by others

Multi-omic analyses reveal PTPN6’s impact on tumor immunity across various cancers

Article Open access 01 April 2025

Pan-cancer analysis of the prognostic and immunological roles of SHP-1/ptpn6

Article Open access 04 October 2024

A comprehensive analysis of PANoptosome to prognosis and immunotherapy response in pan-cancer

Article Open access 08 March 2023

Data availability

The datasets analyzed during the current study are available in the TIMER2.0(http://timer.cistrome.org/),UCSC(https://xenabrowser.net/), UALCAN(https://ualcan.path.uab.edu/analysis-prot.html), GEPIA2(http://gepia2.cancer-pku.cn/analysis), cBioPortal(https://www.cbioportal.org/), CPTAC database (https://proteomics.cancer.gov/programs/cptac), CCLE(https://sites.broadinstitute.org/ccle), TISIDB(cis.hku.hk/TISIDB/) StarBase(https://rnasysu.com/encori/), and GSCALite(https://guolab.wchscu.cn/GSCA/#/).

References

  1. Hanahan, D. Hallmarks of Cancer: New Dimensions. Cancer Discov. 12 (1), 31–46 (2022).

    Google Scholar 

  2. Mala, U., Baral, T. K. & Somasundaram, K. Integrative analysis of cell adhesion molecules in glioblastoma identified prostaglandin F2 receptor inhibitor (PTGFRN) as an essential gene. BMC Cancer. 22 (1), 642 (2022).

    Google Scholar 

  3. Ding, Y. et al. EWI2 and its relatives in Tetraspanin-enriched membrane domains regulate malignancy. Oncogene 42 (12), 861–868 (2023).

    Google Scholar 

  4. Marquez, J. et al. Effect of PTFGRN Expression on the Proteomic Profile of A431 Cells and Determination of the PTGFRN Interactome. ACS Omega. 9 (12), 14381–14387 (2024).

    Google Scholar 

  5. Aguila, B. et al. The Ig superfamily protein PTGFRN coordinates survival signaling in glioblastoma multiforme. Cancer Lett. 462, 33–42 (2019).

    Google Scholar 

  6. Li, T. et al. TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res. 48 (W1), W509–W514 (2020).

    Google Scholar 

  7. Charoentong, P. et al. Pan-cancer Immunogenomic Analyses Reveal Genotype-Immunophenotype Relationships and Predictors of Response to Checkpoint Blockade. Cell. Rep. 18 (1), 248–262 (2017).

    Google Scholar 

  8. Ru, B. et al. TISIDB: an integrated repository portal for tumor-immune system interactions. Bioinformatics 35 (20), 4200–4202 (2019).

    Google Scholar 

  9. Kanehisa, M., Furumichi, M., Sato, Y., Matsuura, Y. & Ishiguro-Watanabe, M. KEGG: biological systems database as a model of the real world. Nucleic Acids Res. 53, D672–D677 (2025).

    Google Scholar 

  10. Kanehisa, M. Toward understanding the origin and evolution of cellular organisms. Protein Sci. 28, 1947–1951 (2019).

    Google Scholar 

  11. Kanehisa, M. & Goto, S. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res. 28, 27–30 (2000).

    Google Scholar 

  12. Tang, Z., Kang, B., Li, C., Chen, T. & Zhang, Z. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 47 (W1), W556–W560 (2019).

    Google Scholar 

  13. Chandrashekar, D. S. et al. UALCAN: An update to the integrated cancer data analysis platform. Neoplasia 25, 18–27 (2022).

    Google Scholar 

  14. Suhas, V., Vasaikar, P., Straub, J., Wang, B. & Zhang LinkedOmics: analyzing multi-omics data within and across 32 cancer types. Nucleic Acids Res. 46 (Issue D1), D956–D963 (2018).

    Google Scholar 

  15. Li, J. H., Liu, S., Zhou, H., Qu, L. H. & Yang, J. H. starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 42 (Database issue), D92–D97 (2014).

    Google Scholar 

  16. Liu, C. J. et al. GSCA: an integrated platform for gene set cancer analysis at genomic, pharmacogenomic and immunogenomic levels. Brief. Bioinform. 24 (1), bbac558 (2023).

    Google Scholar 

  17. Chen, H. W. et al. Prostaglandin F2 receptor inhibitor overexpression predicts advanced who grades and adverse prognosis in human glioma tissue. Chin. J. Physiol. 65 (2), 93–102 (2022).

    Google Scholar 

  18. Jiang, X., Zhang, J. & Huang, Y. Tetraspanins in cell migration. Cell. Adh Migr. 9 (5), 406–415 (2015).

    Google Scholar 

  19. Colin, S. et al. A truncated form of CD9-partner 1 (CD9P-1), GS-168AT2, potently inhibits in vivo tumour-induced angiogenesis and tumour growth. Br. J. Cancer. 105 (7), 1002–1011 (2011).

    Google Scholar 

  20. Guilmain, W. et al. CD9P-1 expression correlates with the metastatic status of lung cancer, and a truncated form of CD9P-1, GS-168AT2, inhibits in vivo tumour growth. Br. J. Cancer. 104 (3), 496–504 (2011).

    Google Scholar 

  21. Aguila, B. et al. The Ig superfamily protein PTGFRN coordinates survival signaling in glioblastoma multiforme. Cancer Lett. 462, 33–42 (2019).

    Google Scholar 

  22. Marquez, J. et al. Effect of PTFGRN Expression on the Proteomic Profile of A431 Cells and Determination of the PTGFRN Interactome. ACS Omega. 9 (12), 14381–14387 (2024).

    Google Scholar 

  23. Aliazis, K. et al. The tumor microenvironment’s role in the response to immune checkpoint blockade. Nat. Cancer. 6 (6), 924–937 (2025).

    Google Scholar 

  24. Huang, G. et al. Tumor suppressor miR-33b-5p regulates cellular function and acts a prognostic biomarker in RCC. Am. J. Transl Res. 12 (7), 3346–3360 (2020).

    Google Scholar 

  25. Rius, F. E. et al. Genome-wide promoter methylation profiling in a cellular model of melanoma progression reveals markers of malignancy and metastasis that predict melanoma survival. Clin. Epigenetics. 14 (1), 68 (2022).

    Google Scholar 

  26. Zhang, S. et al. Truncated PD1 Engineered Gas-Producing Extracellular Vesicles for Ultrasound Imaging and Subsequent Degradation of PDL1 in Tumor Cells. Adv. Sci. (Weinh). 11 (12), e2305891 (2024).

    Google Scholar 

  27. Janes, P. W., Vail, M. E., Ernst, M. & Scott, A. M. Eph Receptors in the Immunosuppressive Tumor Microenvironment. Cancer Res. 81 (4), 801–805 (2021).

    Google Scholar 

  28. Zhang, P. et al. Integrating machine learning and single-cell analysis to uncover lung adenocarcinoma progression and prognostic biomarkers. J. Cell. Mol. Med. 28 (13), e18516 (2024).

    Google Scholar 

  29. Gong, Z. et al. Machine learning identifies TIME subtypes linking EGFR mutations and immune states in lung adenocarcinoma. NPJ Digit. Med. 8 (1), 796 (2025).

    Google Scholar 

  30. El-Gamal, D. et al. PKC-β as a therapeutic target in CLL: PKC inhibitor AEB071 demonstrates preclinical activity in CLL. Blood 124 (9), 1481–1491 (2014).

    Google Scholar 

  31. Yakkala, P. A., Penumallu, N. R., Shafi, S. & Kamal, A. Prospects of Topoisomerase Inhibitors as Promising Anti-Cancer Agents. Pharmaceuticals (Basel). 16 (10), 1456 (2023).

    Google Scholar 

  32. Marquardt, V., Theruvath, J. & Pauck, D. etal. Tacedinaline (CI-994), a class I HDAC inhibitor, targets intrinsic tumor growth and leptomeningeal dissemination in MYC-driven medulloblastoma while making them susceptible to anti-CD47-induced macrophage phagocytosis via NF-kB-TGM2 driven tumor inflammation. J. Immunother Cancer. 11 (1), e005871 (2023).

    Google Scholar 

  33. Thomas, A. & Pommier, Y. Targeting Topoisomerase I in the Era of Precision Medicine. Clin. Cancer Res. 25 (22), 6581–6589 (2019).

    Google Scholar 

Download references

Acknowledgements

The datasets for this study can be found in the public databases TCGA, GTEx, TIMER 2.0, GDSA, and cBioportal.

Funding

The present study was supported by the Hebei Medical Science Research Project (No. 20210980).

Author information

Author notes
  1. These authors contributed equally: Nan Mu and Tianjian Dong.

Authors and Affiliations

  1. Department of Pharmacy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China

    Nan Mu

  2. Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China

    Qingyu Sheng & Qi Zhao

  3. College of Basic Medicine, Hebei Medical University, Shijiazhuang, 050017, China

    Zhuoning Duan

  4. Department of Computed Tomography and Magnetic Resonance Imaging, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China

    Xiangming Wang

  5. Department of Cardiothoracic Surgery, The 980th Hospital of the Chinese People’s Liberation Army Joint Logistics Support Force, Shijiazhuang, 050000, China

    Tianjian Dong

Authors
  1. Nan Mu
    View author publications

    Search author on:PubMed Google Scholar

  2. Tianjian Dong
    View author publications

    Search author on:PubMed Google Scholar

  3. Qingyu Sheng
    View author publications

    Search author on:PubMed Google Scholar

  4. Zhuoning Duan
    View author publications

    Search author on:PubMed Google Scholar

  5. Xiangming Wang
    View author publications

    Search author on:PubMed Google Scholar

  6. Qi Zhao
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Zhao Qi and Dong tianjian performed bioinformatics analysis, and Zhao Qi, Sheng qingyu, Duan zhuoning, Wang xiangming and Dong tinajian co-authored and completed the manuscript. All authors gave final approval to the manuscript.

Corresponding author

Correspondence to Qi Zhao.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary Material 1 (download DOCX )

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mu, N., Dong, T., Sheng, Q. et al. Pan-cancer analysis reveals the oncogenic and immunomodulatory roles of PTGFRN across human cancers. Sci Rep (2026). https://doi.org/10.1038/s41598-026-41027-y

Download citation

  • Received: 21 October 2025

  • Accepted: 17 February 2026

  • Published: 27 February 2026

  • DOI: https://doi.org/10.1038/s41598-026-41027-y

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Keywords

  • TCGA
  • PTGFRN
  • Prognostic biomarker
  • Pan-cancer
  • Tumor-infiltration
Download PDF

Advertisement

Explore content

  • Research articles
  • News & Comment
  • Collections
  • Subjects
  • Follow us on Facebook
  • Follow us on X
  • Sign up for alerts
  • RSS feed

About the journal

  • About Scientific Reports
  • Contact
  • Journal policies
  • Guide to referees
  • Calls for Papers
  • Editor's Choice
  • Journal highlights
  • Open Access Fees and Funding

Publish with us

  • For authors
  • Language editing services
  • Open access funding
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

Scientific Reports (Sci Rep)

ISSN 2045-2322 (online)

nature.com footer links

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2026 Springer Nature Limited

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer