Protein biomarkers in cervicovaginal lavages for detection of endometrial cancer

Biomarker Research

Research

Lyndsay Willmott¹  Dana M. Chase¹  Paweł Łaniewski²  Matthew P. Borst³  Nichole D. Mahnert³  Jamal Mourad³  Melissa M. Herbst-Kralovetz⁴  Haiyan Cui⁵  Denise J. Roe⁵ 

[1] Arizona Center for Cancer Care, 2222 E. Highland Ave, 85016, Phoenix, AZ, USA;College of Medicine – Phoenix, University of Arizona, 425 N. 5th St, 85004, Phoenix, AZ, USA;College of Medicine – Phoenix, University of Arizona, 425 N. 5th St, 85004, Phoenix, AZ, USA;Banner – University Medical Center, 1033 E. McDowell Rd, 85006, Phoenix, AZ, USA;College of Medicine – Phoenix, University of Arizona, 425 N. 5th St, 85004, Phoenix, AZ, USA;UA Cancer Center, University of Arizona, 3838 N. Campbell Ave, 85719, Tucson, AZ, USA;UA Cancer Center, University of Arizona, 3838 N. Campbell Ave, 85719, Tucson, AZ, USA;

关键词: Cervicovaginal microenvironment;    Endometrial cancer;    Minimally to non-invasive diagnostic;    Protein biomarker;    Uterine cancer;    Women’s health;   

DOI  :  10.1186/s40364-022-00438-5

 received in 2022-08-24, accepted in 2022-11-22,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundRates of endometrial cancer (EC) are increasing. For a definitive diagnosis, women undergo various time-consuming and painful medical procedures, such as endometrial biopsy with or without hysteroscopy, and dilation and curettage, which may create a barrier to early detection and treatment, particularly for women with inadequate healthcare access. Thus, there is a need to develop robust EC diagnostics based on non- or minimally-invasive sampling. The objective of this study was to quantify a broad range of immuno-oncology proteins in cervicovaginal lavage (CVL) samples and investigate these proteins as predictive diagnostic biomarkers for EC.MethodsOne hundred ninety-two women undergoing hysterectomy for benign or malignant indications were enrolled in this cross-sectional study. Classification of women to four disease groups: benign conditions (n = 108), endometrial hyperplasia (n = 18), low-grade endometrioid carcinoma (n = 53) and other EC subtypes (n = 13) was based on histopathology of biopsy samples collected after the surgery. CVL samples were collected in the operating room during the standard-of-care hysterectomy procedure. Concentrations of 72 proteins in CVL samples were evaluated using multiplex immunoassays. Global protein profiles were assessed using principal component and hierarchical clustering analyses. The relationships between protein levels and disease groups and disease severity were determined using Spearman correlation, univariate and multivariate receiver operating characteristics, and logistic regression analyses.ResultsWomen with EC and benign conditions exhibited distinctive cervicovaginal protein profiles. Several proteins in CVL samples (e.g., an immune checkpoint protein, TIM-3, growth factors, VEGF, TGF-α, and an anti-inflammatory cytokine, IL-10) discriminated EC from benign conditions, particularly, when tested in combinations with CA19–9, CA125, eotaxin, G-CSF, IL-6, MCP-1, MDC, MCP-3 and TRAIL (sensitivity of 86.1% and specificity of 87.9%). Furthermore, specific biomarkers (e.g., TIM-3, VEGF, TGF-α, TRAIL, MCP-3, IL-15, PD-L2, SCF) associated with histopathological tumor characteristics, including histological type and grade, tumor size, presence and depth of myometrial invasion or mismatch repair protein status, implying their potential utility for disease prognosis or monitoring therapies.ConclusionsThis proof-of-principle study demonstrated that cervicovaginal sampling coupled with multiplex immunoassay technology can offer a minimally to non-invasive method for EC detection.

【 授权许可】

CC BY   
© The Author(s) 2022

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