Skip to content
2000
image of Targeting Phosphatase and Tensin Homolog Deleted on Chromosome 10q23.3 (PTEN) as a Potential Theragnostic Biomarker in Tumors

Abstract

Background

Immunotherapy and targeted therapy have been shown to be notably effective in tumor treatment; however, the mechanism of PTEN function in tumorigenesis, development, and immune response of tumors remains unclear.

Methods

We show that PTEN expression varies significantly in many types of tumors and affects the prognosis of patients with cancer using pan-cancer analysis. Patents were reviewed using the World Intellectual Property Organisation database. We analyzed data from GTEx, CCLE, and TCGA to study the correlation between PTEN expression and prognosis, investigated the correlation between PTEN expression and tumor-infiltrating immune cells using TIMER, analyzed the mutation pattern of PTEN and its correlation with neoantigen expression, TMB, MSI, MMRs, and DNA methyltransferases in tumors, and conducted an enrichment analysis of PTEN in tumors using GSEA.

Results

PTEN expression is related to the levels of infiltrating immune cells, such as B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells. PTEN expression is closely related to neoantigen expression, tumor mutational burden, microsatellite instability, and mismatch repair. The results of a functional enrichment analysis of PTEN showed that PTEN has the potential as a biomarker for precision immunotherapy of tumors.

Conclusion

This study suggests that PTEN may be involved in the recruitment and regulation of immune-infiltrating cells, tumor development, metastasis, prognosis, tumor immune escape, and immunotherapy, indicating its importance in tumor diagnosis and treatment.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/pra/10.2174/0115748928370540250508101925
2025-05-19
2025-11-13

  • From This Site

    /content/journals/pra/10.2174/0115748928370540250508101925
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Chalhoub N. Baker S.J. PTEN and the PI3-kinase pathway in cancer. Annu. Rev. Pathol. 2009 4 1 127 150 10.1146/annurev.pathol.4.110807.092311 18767981
    [Google Scholar]
  2. Cristofano A.D. Pesce B. Cordon-Cardo C. Pandolfi P.P. Pten is essential for embryonic development and tumour suppression. Nat. Genet. 1998 19 4 348 355 10.1038/1235 9697695
    [Google Scholar]
  3. Di Cristofano A. Pandolfi P.P. The multiple roles of PTEN in tumor suppression. Cell 2000 100 4 387 390 10.1016/S0092‑8674(00)80674‑1 10693755
    [Google Scholar]
  4. Lee Y.R. Chen M. Pandolfi P.P. The functions and regulation of the PTEN tumour suppressor: New modes and prospects. Nat. Rev. Mol. Cell Biol. 2018 19 9 547 562 10.1038/s41580‑018‑0015‑0 29858604
    [Google Scholar]
  5. Liu F.S. Molecular carcinogenesis of endometrial cancer. Taiwan. J. Obstet. Gynecol. 2007 46 1 26 32 10.1016/S1028‑4559(08)60102‑3 17389185
    [Google Scholar]
  6. Wu H. Goel V. Haluska F.G. PTEN signaling pathways in melanoma. Oncogene 2003 22 20 3113 3122 10.1038/sj.onc.1206451 12789288
    [Google Scholar]
  7. Guo W. Qiao T. Li T. The role of stem cells in small-cell lung cancer: Evidence from chemoresistance to immunotherapy. Semin. Cancer Biol. 2022 87 160 169 10.1016/j.semcancer.2022.11.006 36371027
    [Google Scholar]
  8. Hu W Yang Y Fan C Ma Z Deng C Li T Lv J Yao W Gao J Clinical and pathological significance of N-Myc downstream-regulated gene 2 (NDRG2) in diverse human cancers. Apoptosis 2016 21 6 675 682
    [Google Scholar]
  9. Hui J. Wang C. Miao Y. Liu R. Xu J. The pancancer landscape of Wnt family expression reveals potential biomarkers in urinary system tumors. Cancer Gene Ther. 2021 28 9 1035 1045 10.1038/s41417‑020‑00273‑6 33311568
    [Google Scholar]
  10. Li S. Dong R. Kang Z. Li H. Wu X. Li T. Exosomes: Another intercellular lipometabolic communication mediators in digestive system neoplasms? Cytokine Growth Factor Rev. 2023 73 93 100 10.1016/j.cytogfr.2023.06.005 37541791
    [Google Scholar]
  11. Liu Y. Yang C. Chen S. Liu W. Liang J. He S. Hui J. Cancer-derived exosomal miR-375 targets DIP2C and promotes osteoblastic metastasis and prostate cancer progression by regulating the Wnt signaling pathway. Cancer Gene Ther. 2023 30 3 437 449 36434177
    [Google Scholar]
  12. Zhang X. Yu S. Li X. Wen X. Liu S. Zu R. Ren H. Li T. Yang C. Luo H. Research progress on the interaction between oxidative stress and platelets: Another avenue for cancer? Pharmacol. Res. 2023 191 106777 10.1016/j.phrs.2023.106777 37080257
    [Google Scholar]
  13. Zhou M. Liang J. Hui J. Xu J. Inflammation-related indicators have a potential to increase overall quality of the prostate cancer management: a narrative review. Transl. Androl. Urol. 2023 12 5 809 822 10.21037/tau‑23‑55 37305618
    [Google Scholar]
  14. Hu C. Cao Y. Li P. Tang X. Yang M. Gu S. Xiong K. Li T. Xiao T. Oleanolic acid induces autophagy and apoptosis via the AMPK-mTOR signaling pathway in colon cancer. J. Oncol. 2021 2021 1 17 10.1155/2021/8281718 34326874
    [Google Scholar]
  15. Wu X. Yan F. Wang L. Sun G. Liu J. Qu M. Wang Y. Li T. MicroRNA: Another pharmacological avenue for colorectal cancer? Front. Cell Dev. Biol. 2020 8 812 10.3389/fcell.2020.00812 32984321
    [Google Scholar]
  16. Liu Y. Chen S. Guo K. Ma S. Wang X. Liu Q. Yan R. Huang Y. Li T. He S. Hui J. Osteoblast‐derived exosomal miR ‐140‐3p targets ACER2 and increases the progression of prostate cancer via the AKT/mTOR pathway‐mediated inhibition of autophagy. FASEB J. 2024 38 23 e70206 10.1096/fj.202401480R 39625343
    [Google Scholar]
  17. Cantley L.C. Neel B.G. New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc. Natl. Acad. Sci. USA 1999 96 8 4240 4245 10.1073/pnas.96.8.4240 10200246
    [Google Scholar]
  18. Simpson L. Parsons R. PTEN: Life as a tumor suppressor. Exp. Cell Res. 2001 264 1 29 41 10.1006/excr.2000.5130 11237521
    [Google Scholar]
  19. Hollander M.C. Blumenthal G.M. Dennis P.A. PTEN loss in the continuum of common cancers, rare syndromes and mouse models. Nat. Rev. Cancer 2011 11 4 289 301 10.1038/nrc3037 21430697
    [Google Scholar]
  20. Ortega-Molina A. Serrano M. PTEN in cancer, metabolism, and aging. Trends Endocrinol. Metab. 2013 24 4 184 189 10.1016/j.tem.2012.11.002 23245767
    [Google Scholar]
  21. Song M.S. Salmena L. Pandolfi P.P. The functions and regulation of the PTEN tumour suppressor. Nat. Rev. Mol. Cell Biol. 2012 13 5 283 296 10.1038/nrm3330 22473468
    [Google Scholar]
  22. Alimonti A. Carracedo A. Clohessy J.G. Trotman L.C. Nardella C. Egia A. Salmena L. Sampieri K. Haveman W.J. Brogi E. Richardson A.L. Zhang J. Pandolfi P.P. Subtle variations in Pten dose determine cancer susceptibility. Nat. Genet. 2010 42 5 454 458 10.1038/ng.556 20400965
    [Google Scholar]
  23. Álvarez-Garcia V. Tawil Y. Wise H.M. Leslie N.R. Mechanisms of PTEN loss in cancer: It’s all about diversity. Semin. Cancer Biol. 2019 59 66 79 10.1016/j.semcancer.2019.02.001 30738865
    [Google Scholar]
  24. Cerezo L Cardenes H Michael H Molecular alterations in the pathogenesis of endometrial adenocarcinoma. Therapeutic implications. Clin Transl Oncol 2006 8 4 231 241
    [Google Scholar]
  25. Hayashi K. Yandell D.W. How sensitive is PCR-SSCP? Hum. Mutat. 1993 2 5 338 346 10.1002/humu.1380020503 8257985
    [Google Scholar]
  26. Sun H. Enomoto T. Fujita M. Wada H. Yoshino K. Ozaki K. Nakamura T. Murata Y. Mutational analysis of the PTEN gene in endometrial carcinoma and hyperplasia. Am. J. Clin. Pathol. 2001 115 1 32 38 10.1309/7JX6‑B9U9‑3P0R‑EQNY 11190805
    [Google Scholar]
  27. Ohtani H. Focus on TILs: Prognostic significance of tumor infiltrating lymphocytes in human colorectal cancer. Cancer Immun. 2007 7 4 17311363
    [Google Scholar]
  28. Azimi F. Scolyer R.A. Rumcheva P. Moncrieff M. Murali R. McCarthy S.W. Saw R.P. Thompson J.F. Tumor-infiltrating lymphocyte grade is an independent predictor of sentinel lymph node status and survival in patients with cutaneous melanoma. J. Clin. Oncol. 2012 30 21 2678 2683 10.1200/JCO.2011.37.8539 22711850
    [Google Scholar]
  29. Conciatori F. Bazzichetto C. Falcone I. Ciuffreda L. Ferretti G. Vari S. Ferraresi V. Cognetti F. Milella M. PTEN function at the interface between cancer and tumor microenvironment: Implications for response to immunotherapy. Int. J. Mol. Sci. 2020 21 15 5337 10.3390/ijms21155337 32727102
    [Google Scholar]
  30. Xu C. Fillmore C.M. Koyama S. Wu H. Zhao Y. Chen Z. Herter-Sprie G.S. Akbay E.A. Tchaicha J.H. Altabef A. Reibel J.B. Walton Z. Ji H. Watanabe H. Jänne P.A. Castrillon D.H. Rustgi A.K. Bass A.J. Freeman G.J. Padera R.F. Dranoff G. Hammerman P.S. Kim C.F. Wong K.K. Loss of Lkb1 and Pten leads to lung squamous cell carcinoma with elevated PD-L1 expression. Cancer Cell 2014 25 5 590 604 10.1016/j.ccr.2014.03.033 24794706
    [Google Scholar]
  31. Mittendorf E.A. Philips A.V. Meric-Bernstam F. Qiao N. Wu Y. Harrington S. Su X. Wang Y. Gonzalez-Angulo A.M. Akcakanat A. Chawla A. Curran M. Hwu P. Sharma P. Litton J.K. Molldrem J.J. Alatrash G. PD-L1 expression in triple-negative breast cancer. Cancer Immunol. Res. 2014 2 4 361 370 10.1158/2326‑6066.CIR‑13‑0127 24764583
    [Google Scholar]
  32. Zhang J. Shi Z. Xu X. Yu Z. Mi J. The influence of microenvironment on tumor immunotherapy. FEBS J. 2019 286 21 4160 4175 10.1111/febs.15028 31365790
    [Google Scholar]
  33. Piro G. Carbone C. Carbognin L. Pilotto S. Ciccarese C. Iacovelli R. Milella M. Bria E. Tortora G. Revising PTEN in the era of immunotherapy: New perspectives for an old story. Cancers 2019 11 10 1525 10.3390/cancers11101525 31658667
    [Google Scholar]
  34. Trimboli A.J. Cantemir-Stone C.Z. Li F. Wallace J.A. Merchant A. Creasap N. Thompson J.C. Caserta E. Wang H. Chong J.L. Naidu S. Wei G. Sharma S.M. Stephens J.A. Fernandez S.A. Gurcan M.N. Weinstein M.B. Barsky S.H. Yee L. Rosol T.J. Stromberg P.C. Robinson M.L. Pepin F. Hallett M. Park M. Ostrowski M.C. Leone G. Pten in stromal fibroblasts suppresses mammary epithelial tumours. Nature 2009 461 7267 1084 1091 10.1038/nature08486 19847259
    [Google Scholar]
  35. Bezzi M. Seitzer N. Ishikawa T. Reschke M. Chen M. Wang G. Mitchell C. Ng C. Katon J. Lunardi A. Signoretti S. Clohessy J.G. Zhang J. Pandolfi P.P. Diverse genetic-driven immune landscapes dictate tumor progression through distinct mechanisms. Nat. Med. 2018 24 2 165 175 10.1038/nm.4463 29309058
    [Google Scholar]
  36. Xu W.X. Zhang J. Hua Y.T. Yang S.J. Wang D.D. Tang J.H. An integrative pan-cancer analysis revealing LCN2 as an oncogenic immune protein in tumor microenvironment. Front. Oncol. 2020 10 605097 10.3389/fonc.2020.605097 33425761
    [Google Scholar]
  37. Song J. Han J. Liu F. Chen X. Qian S. Wang Y. Jia Z. Duan X. Zhang X. Zhu J. Systematic analysis of coronavirus disease 2019 (COVID-19) receptor ACE2 in malignant tumors: Pan-cancer analysis. Front. Mol. Biosci. 2020 7 569414 10.3389/fmolb.2020.569414 33195415
    [Google Scholar]
  38. Roh W. Chen P.L. Reuben A. Spencer C.N. Prieto P.A. Miller J.P. Gopalakrishnan V. Wang F. Cooper Z.A. Reddy S.M. Gumbs C. Little L. Chang Q. Chen W.S. Wani K. De Macedo M.P. Chen E. Austin-Breneman J.L. Jiang H. Roszik J. Tetzlaff M.T. Davies M.A. Gershenwald J.E. Tawbi H. Lazar A.J. Hwu P. Hwu W.J. Diab A. Glitza I.C. Patel S.P. Woodman S.E. Amaria R.N. Prieto V.G. Hu J. Sharma P. Allison J.P. Chin L. Zhang J. Wargo J.A. Futreal P.A. Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance. Sci. Transl. Med. 2017 9 379 eaah3560 10.1126/scitranslmed.aah3560 28251903
    [Google Scholar]
  39. Chen H. Chong W. Teng C. Yao Y. Wang X. Li X. The immune response‐related mutational signatures and driver genes in non‐small‐cell lung cancer. Cancer Sci. 2019 110 8 2348 2356 10.1111/cas.14113 31222843
    [Google Scholar]
  40. Schumacher T.N. Schreiber R.D. Neoantigens in cancer immunotherapy. Science 2015 348 6230 69 74 10.1126/science.aaa4971 25838375
    [Google Scholar]
  41. Aldous A.R. Dong J.Z. Personalized neoantigen vaccines: A new approach to cancer immunotherapy. Bioorg. Med. Chem. 2018 26 10 2842 2849 10.1016/j.bmc.2017.10.021 29111369
    [Google Scholar]
  42. Chalmers Z.R. Connelly C.F. Fabrizio D. Gay L. Ali S.M. Ennis R. Schrock A. Campbell B. Shlien A. Chmielecki J. Huang F. He Y. Sun J. Tabori U. Kennedy M. Lieber D.S. Roels S. White J. Otto G.A. Ross J.S. Garraway L. Miller V.A. Stephens P.J. Frampton G.M. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med. 2017 9 1 34 10.1186/s13073‑017‑0424‑2 28420421
    [Google Scholar]
  43. Lopez G. Noale M. Corti C. Gaudioso G. Sajjadi E. Venetis K. Gambini D. Runza L. Costanza J. Pesenti C. Grossi F. Maggi S. Ferrero S. Bosari S. Fusco N. PTEN expression as a complementary biomarker for mismatch repair testing in breast cancer. Int. J. Mol. Sci. 2020 21 4 1461 10.3390/ijms21041461 32098071
    [Google Scholar]
  44. Gao C. Zhuang J. Zhou C. Liu L. Liu C. Li H. Zhao M. Liu G. Sun C. Developing DNA methylation‐based prognostic biomarkers of acute myeloid leukemia. J. Cell. Biochem. 2018 119 12 10041 10050 10.1002/jcb.27336 30171717
    [Google Scholar]
  45. Budovsky A. Muradian K.K. Fraifeld V.E. From disease-oriented to aging/longevity-oriented studies. Rejuvenation Res. 2006 9 2 207 210 10.1089/rej.2006.9.207 16706644
    [Google Scholar]
  46. McLoughlin N.M. Mueller C. Grossmann T.N. The therapeutic potential of PTEN modulation: Targeting strategies from gene to protein. Cell Chem. Biol. 2018 25 1 19 29 10.1016/j.chembiol.2017.10.009 29153852
    [Google Scholar]
  47. Vidotto T. Melo C.M. Castelli E. Koti M. dos Reis R.B. Squire J.A. Emerging role of PTEN loss in evasion of the immune response to tumours. Br. J. Cancer 2020 122 12 1732 1743 10.1038/s41416‑020‑0834‑6 32327707
    [Google Scholar]
  48. Chow J.T.S. Salmena L. Recent advances in PTEN signalling axes in cancer. Fac. Rev. 2020 9 31 10.12703/r/9‑31 33659963
    [Google Scholar]
  49. Aguilar M. Chen H. Rivera-Colon G. Niu S. Carrick K. Gwin K. Cuevas I.C. Sahoo S.S. Li H.D. Zhang S. Zheng W. Lucas E. Castrillon D.H. Reliable identification of endometrial precancers through combined Pax2, β-Catenin, and Pten immunohistochemistry. Am. J. Surg. Pathol. 2022 46 3 404 414 10.1097/PAS.0000000000001810 34545858
    [Google Scholar]
  50. Ren G. Chen J. Pu Y. Yang E.J. Tao S. Mou P.K. Chen L.J. Zhu W. Chan K.L. Luo G. Deng C. Shim J.S. BET inhibition induces synthetic lethality in PTEN deficient colorectal cancers via dual action on p21 CIP1/WAF1. Int. J. Biol. Sci. 2024 20 6 1978 1991 10.7150/ijbs.91867 38617536
    [Google Scholar]
  51. Zhang H. Li Y. The Patent Landscape of mTOR and PTEN Targets. Recent Adv. Antiinfect. Drug Discov. 2024 19 2 104 118 10.2174/2772434418666230427164556 37132311
    [Google Scholar]
  52. PEIZHAN C. Application of multiple genes as EGFR monoclonal antibody-based drug drug-resistance markers. CN110004229A 2019
    [Google Scholar]
  53. FEI M. Biomarker for breast cancer detection, kit and application thereof. Patent CN115747338A 2023
  54. JIN Z. EGFR inhibitors (1H-pyrrolo [2,3-b ] pyridin-1-yl) pyrimidin-2-yl-amino-phenyl-acrylamides for the treatment of brain tumors. Patent CN117979968A 2024
/content/journals/pra/10.2174/0115748928370540250508101925
Loading
Targeting Phosphatase and Tensin Homolog Deleted on Chromosome 10q23.3 (PTEN) as a Potential Theragnostic Biomarker in Tumors
Bentham Science Publishers ; https://doi.org/10.2174/0115748928370540250508101925
/content/journals/pra/10.2174/0115748928370540250508101925
/content/journals/pra/10.2174/0115748928370540250508101925
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s website along with the published article.

file format download Download

  • Article Type:     Research Article
Keywords: tumor ; immune infiltration ; PTEN ; mutation ; cancer ; biomarkers ; prognosis ; immunotherapy

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test