Proteomic Identification of Small Extracellular Vesicle Proteins LAMB1 and Histone H4 for Prostate Cancer Diagnosis and Risk Stratiﬁcation

Sep 21, 2026

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Proteomic profiling identifies small extracellular vesicle (sEV) protein biomarkers for prostate cancer (PCa) diagnosis and risk stratification, addressing limitations of serum PSA testing. A label-free LC-MS/MS proteomics workflow screens PCa cell lines for candidate sEV proteins, followed by validation using plasma and urine samples across PCa stages. Targeted parallel reaction monitoring, western blotting, and ELISA confirm biomarker performance, while tissue microarray analysis supports associations with cancer origin. sEV LAMB1 shows elevated plasma levels in metastatic PCa, whereas sEV Histone H4 is increased in urine of high-risk PCa, outperforming PSA in specificity and sensitivity for metastatic diagnosis, progression monitoring, and stratification.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages17

Reading Time43 min

AccessFree to download

Introduction

Clinical challenge of PSA-based diagnosis and risk stratification

Need for reliable PCa biomarkers

Methods and validation overview

Label-free LC-MS/MS discovery in PCa cell lines

Targeted proteomics and immunoassays in plasma/urine

Tissue microarray confirmation

RESEARCH ARTICLE [www.advancedscience.com](www.advancedscience.com) Proteomic Identiﬁcation of Small Extracellular Vesicle Proteins LAMB1 and Histone H4 for Prostate Cancer Diagnosis and Risk Stratiﬁcation Bairen Pang, Qi Wang, Haotian Chen, Zhihan Liu, Meng Han, Jie Gong, Liang Yue, Xuan Ding, Suying Wang, Zejun Yan, Yingzhi Chen, David Malouf, Joseph Bucci, Tiannan Guo, Cheng Zhou,* Junhui Jiang,* and Yong Li* Diagnosis and stratiﬁcation of prostate cancer (PCa) patients using the prostate-speciﬁc antigen (PSA) test is challenging. Extracellular vesicles (EVs), as a new star of liquid biopsy, has attracted interest to complement inaccurate PSA screening and invasiveness oftissue biopsy. In this study, a panel of potential small EV (sEV) protein biomarkers is identiﬁed from PCa cell lines using label-free LC-MS/MS proteomics. These biomarkers underwent further validation with plasma and urine samples from diﬀerent PCa stages through parallel reaction monitoring-based targeted proteomics, western blotting, and ELISA. Additionally, a tissue microarray containing cancerous and noncancerous tissues is screened to provide additional evidence of selected sEV proteins associated with cancer origin. Results indicate that sEV protein LAMB1 is highly expressed in human plasma of metastatic PCa patients compared with localised PCa patients and control subjects, while sEV protein Histone H4 is highly expressed in human urine of high-risk PCa patients compared to low-risk PCa patients and control subjects. These two sEV proteins demonstrate higher speciﬁcity and sensitivity than the PSA test and show promise for metastatic PCa diagnosis, progression monitoring, and risk stratiﬁcation. last decade. [2] Several studies indicate that detecting PCa at an early stage reduces mortality.[3] Despite surgery and radiation therapy that can treat localised disease, up to 30% of treated PCa patients suﬀer relapse and metastasis. There is no curative therapy for metastatic PCa (mPCa) and median survival is ≈1 year. The survival of PCa patients is largely related to tumour stage and grade. [4] Treatment options for diﬀerent stages of PCa patients vary with risk grade. A major clinical challenge in PCa management is posed by the inability of current diagnostic tests, such as serum prostatespeciﬁc antigen (PSA) testing, digital rectal examination, and histopathologic grading of tissues, to discern between indolent and aggressive disease. [5] A major knowledge gap for PCa research is the lack of suitable biomarkers for accurate diagnosis, therapeutic stratiﬁcation, and predicting or monitoring metastasis. The beneﬁts of risk stratiﬁcation are to assess the overall 1. Introduction Prostate cancer (PCa) is the second most common cancer in men and nearly one and a half million men are diagnosed annually world-wide. [1] More alarming still, the percentage of patients with metastatic disease at diagnosis has increased by 25% over the progression of metastases for localised cancer, select optimal treatment options, and predict the likelihood of recurrence following deﬁnitive local therapy. Therefore, improving the screening and early diagnosis of PCa, especially metastatic disease, are of great importance in designing reasonable treatment plans and improving the prognosis of patients. B. Pang, H. Chen, Z. Liu, M. Han, J. Gong, Z. Yan, Y. Chen, C. Zhou, J. Jiang Department of Urology The First Aﬃliated Hospital of Ningbo University Ningbo, Zhejiang 315010, China E-mail: [fyyzhoucheng@nbu.edu.cn](fyyzhoucheng@nbu.edu.cn); [fyyjiangjunhui@nbu.edu.cn](fyyjiangjunhui@nbu.edu.cn) The ORCID identiﬁcation number(s) for the author(s) of this article can be found under [https://doi.org/10.1002/advs.202402509](https://doi.org/10.1002/advs.202402509)[ ](https://doi.org/10.1002/advs.202402509)© 2024 The Authors. Advanced Science published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution Lic

FAQs

Why are PSA tests insufficient for prostate cancer diagnosis and risk stratification?

PSA testing has limited specificity and sensitivity, leading to missed cases and substantial overdiagnosis and overtreatment. It cannot reliably distinguish indolent from aggressive disease or accurately predict metastasis risk.

How were candidate small EV protein biomarkers identified and validated?

Candidate biomarkers were identified from PCa cell lines using label-free LC-MS/MS proteomics. They were then validated with plasma and urine samples using parallel reaction monitoring-based targeted proteomics, western blotting, and ELISA.

What roles do LAMB1 and Histone H4 play as biomarkers in different PCa risk groups?

sEV protein LAMB1 is highly expressed in human plasma of metastatic PCa patients compared with localized cases and controls. sEV protein Histone H4 is highly expressed in human urine of high-risk PCa patients compared with low-risk cases and controls.

Sep 21, 2026

Uploaded by Violet