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Immunometabolic profiling of cervicovaginal lavages identifies key signatures associated with adenomyosis.

ABSTRACT: Adenomyosis is a burdensome gynecologic condition that is associated with pelvic pain, dysmenorrhea, and abnormal uterine bleeding, leading to a negative impact on quality of life; and yet is often left undiagnosed. We recruited 108 women undergoing hysterectomy for benign gynecologic conditions and collected non-invasive cervicovaginal lavage samples for immunometabolic profiling. Patients were grouped according to adenomyosis status. We investigated the levels of 72 soluble immune proteins and >900 metabolites using multiplex immunoassays and an untargeted global metabolomics platform. There were statistically significant alterations in the levels of several immune proteins and a large quantity of metabolites, particularly cytokines related to type II immunity and amino acids, respectively. Enrichment analysis revealed that pyrimidine metabolism, carnitine synthesis, and histidine/histamine metabolism were significantly upregulated pathways in adenomyosis. This study demonstrates utility of non-invasive sampling combined with immunometabolic profiling for adenomyosis detection and a greater pathophysiological understanding of this enigmatic condition.

SUBMITTER: Lorentzen GM

PROVIDER: S-EPMC9676393 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Immunometabolic profiling of cervicovaginal lavages identifies key signatures associated with adenomyosis.

Lorentzen Georgia M GM Łaniewski Paweł P Cui Haiyan H Roe Denise J DJ Mourad Jamal J Mahnert Nichole D ND Farland Leslie V LV Herbst-Kralovetz Melissa M MM

iScience 20221104 12

Adenomyosis is a burdensome gynecologic condition that is associated with pelvic pain, dysmenorrhea, and abnormal uterine bleeding, leading to a negative impact on quality of life; and yet is often left undiagnosed. We recruited 108 women undergoing hysterectomy for benign gynecologic conditions and collected non-invasive cervicovaginal lavage samples for immunometabolic profiling. Patients were grouped according to adenomyosis status. We investigated the levels of 72 soluble immune proteins and ...[more]

PMID: 36419846

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Project description: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.

Dataset Information

Immunometabolic profiling of cervicovaginal lavages identifies key signatures associated with adenomyosis.

Publications

Immunometabolic profiling of cervicovaginal lavages identifies key signatures associated with adenomyosis.

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