Detection of p53 aggregates in plasma of glioma patients

Yunzhao Wu; Jeff Y. L. Lam; Matthaios Pitoulias; Dorothea Böken; Ziwei Zhang; Renuka Chintapalli; Emre Fertan; Zengjie Xia; John S. H. Danial; Gemma Tsang-Pells; Emily Fysh; Linda Julian; Kevin M. Brindle; Richard Mair; David Klenerman

doi:10.1038/s43856-025-00918-3

Detection of p53 aggregates in plasma of glioma patients

Yunzhao Wu
, Jeff Y. L. Lam
, Matthaios Pitoulias
, Dorothea Böken
, Ziwei Zhang
, Renuka Chintapalli
, Emre Fertan
, Zengjie Xia
, John S. H. Danial
, Gemma Tsang-Pells
, Emily Fysh
, Linda Julian
, Kevin M. Brindle
, Richard Mair^*
, David Klenerman^*

^*Corresponding author for this work

School of Physics and Astronomy

Research output: Contribution to journal › Article › peer-review

Abstract

Background
The tumour-suppressor protein p53 can form amyloid aggregates resulting in loss of tumour-suppressing functions and leading to tumour formation. The detection of p53 aggregates in cancer cells has been demonstrated but these aggregates have not been detected in liquid biopsies to date, due to the lack of sufficiently sensitive methods.

Methods
We developed an ultrasensitive immunoassay based on the single-molecule array (SiMoA) technology to detect p53 aggregates in plasma, based on antibody capture of the aggregates. We confirmed that the assay detects p53 aggregates using super-resolution imaging. We then investigated the p53 aggregate concentrations in the plasma of 190 pre-surgery glioblastoma (GB) patients and 22 controls using this assay.

Results
We found that the plasma p53 aggregate levels are significantly elevated in pre-surgery GB patients’ plasma compared to controls. Longitudinal study further reveals that p53 aggregate levels may increase before GB recurrence and decrease following treatment. We also observed raised p53 aggregate concentrations in the plasma of cancer patients with brain metastases.

Conclusions
This study demonstrates the detection of p53 aggregates in liquid biopsies. Our findings highlight the potential of p53 aggregates as a novel biomarker for glioblastoma.

Original language	English
Article number	195
Number of pages	11
Journal	Communications Medicine
Volume	5
DOIs	https://doi.org/10.1038/s43856-025-00918-3
Publication status	Published - 23 May 2025

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@article{56c7338f2c1f4958aa5ce7e71707705b,

title = "Detection of p53 aggregates in plasma of glioma patients",

abstract = "Background The tumour-suppressor protein p53 can form amyloid aggregates resulting in loss of tumour-suppressing functions and leading to tumour formation. The detection of p53 aggregates in cancer cells has been demonstrated but these aggregates have not been detected in liquid biopsies to date, due to the lack of sufficiently sensitive methods. Methods We developed an ultrasensitive immunoassay based on the single-molecule array (SiMoA) technology to detect p53 aggregates in plasma, based on antibody capture of the aggregates. We confirmed that the assay detects p53 aggregates using super-resolution imaging. We then investigated the p53 aggregate concentrations in the plasma of 190 pre-surgery glioblastoma (GB) patients and 22 controls using this assay. Results We found that the plasma p53 aggregate levels are significantly elevated in pre-surgery GB patients{\textquoteright} plasma compared to controls. Longitudinal study further reveals that p53 aggregate levels may increase before GB recurrence and decrease following treatment. We also observed raised p53 aggregate concentrations in the plasma of cancer patients with brain metastases. Conclusions This study demonstrates the detection of p53 aggregates in liquid biopsies. Our findings highlight the potential of p53 aggregates as a novel biomarker for glioblastoma.",

author = "Yunzhao Wu and Lam, \{Jeff Y. L.\} and Matthaios Pitoulias and Dorothea B{\"o}ken and Ziwei Zhang and Renuka Chintapalli and Emre Fertan and Zengjie Xia and Danial, \{John S. H.\} and Gemma Tsang-Pells and Emily Fysh and Linda Julian and Brindle, \{Kevin M.\} and Richard Mair and David Klenerman",

note = "Funding: This work is supported by the Primer Award of Cancer Research UK (EDDPMA-May23/100016). J.Y.L.L. is supported by the Croucher Foundation Limited (Hong Kong).",

year = "2025",

month = may,

day = "23",

doi = "10.1038/s43856-025-00918-3",

language = "English",

volume = "5",

journal = "Communications Medicine",

issn = "2730-664X",

publisher = "Springer Nature",

}

TY - JOUR

T1 - Detection of p53 aggregates in plasma of glioma patients

AU - Wu, Yunzhao

AU - Lam, Jeff Y. L.

AU - Pitoulias, Matthaios

AU - Böken, Dorothea

AU - Zhang, Ziwei

AU - Chintapalli, Renuka

AU - Fertan, Emre

AU - Xia, Zengjie

AU - Danial, John S. H.

AU - Tsang-Pells, Gemma

AU - Fysh, Emily

AU - Julian, Linda

AU - Brindle, Kevin M.

AU - Mair, Richard

AU - Klenerman, David

N1 - Funding: This work is supported by the Primer Award of Cancer Research UK (EDDPMA-May23/100016). J.Y.L.L. is supported by the Croucher Foundation Limited (Hong Kong).

PY - 2025/5/23

Y1 - 2025/5/23

N2 - Background The tumour-suppressor protein p53 can form amyloid aggregates resulting in loss of tumour-suppressing functions and leading to tumour formation. The detection of p53 aggregates in cancer cells has been demonstrated but these aggregates have not been detected in liquid biopsies to date, due to the lack of sufficiently sensitive methods. Methods We developed an ultrasensitive immunoassay based on the single-molecule array (SiMoA) technology to detect p53 aggregates in plasma, based on antibody capture of the aggregates. We confirmed that the assay detects p53 aggregates using super-resolution imaging. We then investigated the p53 aggregate concentrations in the plasma of 190 pre-surgery glioblastoma (GB) patients and 22 controls using this assay. Results We found that the plasma p53 aggregate levels are significantly elevated in pre-surgery GB patients’ plasma compared to controls. Longitudinal study further reveals that p53 aggregate levels may increase before GB recurrence and decrease following treatment. We also observed raised p53 aggregate concentrations in the plasma of cancer patients with brain metastases. Conclusions This study demonstrates the detection of p53 aggregates in liquid biopsies. Our findings highlight the potential of p53 aggregates as a novel biomarker for glioblastoma.

AB - Background The tumour-suppressor protein p53 can form amyloid aggregates resulting in loss of tumour-suppressing functions and leading to tumour formation. The detection of p53 aggregates in cancer cells has been demonstrated but these aggregates have not been detected in liquid biopsies to date, due to the lack of sufficiently sensitive methods. Methods We developed an ultrasensitive immunoassay based on the single-molecule array (SiMoA) technology to detect p53 aggregates in plasma, based on antibody capture of the aggregates. We confirmed that the assay detects p53 aggregates using super-resolution imaging. We then investigated the p53 aggregate concentrations in the plasma of 190 pre-surgery glioblastoma (GB) patients and 22 controls using this assay. Results We found that the plasma p53 aggregate levels are significantly elevated in pre-surgery GB patients’ plasma compared to controls. Longitudinal study further reveals that p53 aggregate levels may increase before GB recurrence and decrease following treatment. We also observed raised p53 aggregate concentrations in the plasma of cancer patients with brain metastases. Conclusions This study demonstrates the detection of p53 aggregates in liquid biopsies. Our findings highlight the potential of p53 aggregates as a novel biomarker for glioblastoma.

UR - https://www.scopus.com/pages/publications/105005982189

U2 - 10.1038/s43856-025-00918-3

DO - 10.1038/s43856-025-00918-3

M3 - Article

AN - SCOPUS:105005982189

SN - 2730-664X

VL - 5

JO - Communications Medicine

JF - Communications Medicine

M1 - 195

ER -

Detection of p53 aggregates in plasma of glioma patients

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