Immunometabolic profiling of cervicovaginal lavages identifies key signatures associated with adenomyosis

Lorentzen, Georgia M.; Łaniewski, Paweł; Cui, Haiyan; Roe, Denise J.; Mourad, J.; Mahnert, Nichole; Farland, Leslie V.; Herbst-Kralovetz, Melissa M.

doi:10.1016/j.isci.2022.105508

Cited by 4 publications

(6 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The literature shows glutamate enhances cancer cell proliferation in endometrial and breast cancer in vitro ( 44 , 45 ). Histidine metabolism was highly altered, similarly to our work using CVLs from participants with adenomyosis, relating to uterine contractility ( 20 ). Tryptophan metabolism has already been well established to be increased in cancer, due to its ability to aid immune suppression ( 46 ).…”

Section: Discussionsupporting

confidence: 67%

“…Our results indicate that metabolite levels are indicative of tumor characteristics, particularly tumor size and myometrial invasion, particularly pyrimidine and purine metabolites (2′-deoxyuridine, 5-methyluridine, 5,6-dihydrothymine, adenosine, AMP, cytidine diphosphate, and uridine). Previous work has shown these metabolite groups were related to excess cellular proliferation in adenomyosis ( 20 ). Furthermore, a number of these metabolites [PC (P-16:0/20:4), PC (P-16:0/16:0), and uridine] were also potential biomarkers for cervical cancer in our previous study ( 18 ), highlighting potential links between cervical and endometrial cancer progression.…”

Section: Discussionmentioning

confidence: 90%

“…For example, our results show that metabolites relating to tryptophan and histidine metabolism are enriched in both endometrial cancer and adenomyosis (a non-malignant gynecologic condition affecting the endometrium; ref. 20 ).…”

Section: Discussionmentioning

confidence: 99%

“…Soluble metabolites in CVL samples were quantified using a global metabolomics platform at Metabolon, Inc. as previously described ( 20 ). Briefly, the Metabolon’s platform utilized a Waters ACQUITY ultra-performance liquid chromatography and a Thermo Scientific Q-exactive high-resolution/accurate mass spectrometer interfaced with a heated electrospray ionization source and Orbitrap mass analyzer operated at 35,000 mass resolution.…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Cervicovaginal Metabolome and Tumor Characteristics for Endometrial Cancer Detection and Risk Stratification

Lorentzen,

Łaniewski,

Cui

et al. 2024

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Endometrial cancer is highly prevalent and lacking non-invasive diagnostic techniques. Diagnosis depends on histological investigation of biopsy samples. Serum biomarkers for endometrial cancer have lacked sensitivity and specificity. The objective of this study was to investigate the cervicovaginal environment to improve understanding of metabolic reprogramming related to endometrial cancer and identify potential biomarker candidates for non-invasive diagnostic and prognostic tests. Experimental Design: Cervicovaginal lavages were collected from 192 participants with endometrial cancer (n=66) and non-malignant conditions (n=108), and global untargeted metabolomics was performed. Using the metabolite data (n=920), we completed a multivariate biomarker discovery analysis. Results: We analyzed grade 1/2 endometrioid carcinoma (n=53) and other endometrial cancer subtypes (n=13) to identify shared and unique metabolic signatures between the subtypes. When compared to non-malignant conditions, downregulation of proline (p<0.0001), tryptophan (p<0.0001), and glutamate (p<0.0001) was found among both endometrial cancer groups, relating to key hallmarks of cancer including immune suppression and redox balance. Upregulation (q<0.05) of sphingolipids, fatty acids, and glycerophospholipids was observed in endometrial cancer in a type-specific manner. Furthermore, cervicovaginal metabolites related to tumor characteristics, including tumor size and myometrial invasion. Conclusions: Our findings provide insights into understanding the endometrial cancer metabolic landscape and improvement into diagnosis. The metabolic dysregulation described in this paper linked specific metabolites and pathophysiological mechanisms including cellular proliferation, energy supply, and invasion of neighbouring tissues. Furthermore, cervicovaginal metabolite levels related to tumor characteristics, which are used for risk stratification. Overall, development of non-invasive diagnostic can improve both the acceptability and accessibility of diagnosis.

show abstract

Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Cervicovaginal Metabolome and Tumor Characteristics for Endometrial Cancer Detection and Risk Stratification

Lorentzen,

Łaniewski,

Cui

et al. 2024

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…Thus, CVL sampling, as demonstrated in this study, can offer an attractive, nonto minimally invasive method of EC diagnosis. Previously, liquid from the Papanicolaou test also showed a promising potential for EC detection by genetic analyses of circulating tumor DNA (called PapSEEK) [37], further demonstrating that minimally invasive cervicovaginal sampling has immense potential for detecting EC and other uterine conditions [38].…”

Section: Discussionmentioning

confidence: 99%

Protein biomarkers in cervicovaginal lavages for detection of endometrial cancer

et al. 2022

Self Cite

View full text Add to dashboard Cite

Background Rates 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. Methods One 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. Results Women 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. Conclusions This proof-of-principle study demonstrated that cervicovaginal sampling coupled with multiplex immunoassay technology can offer a minimally to non-invasive method for EC detection.

show abstract

Meclizine improves endometrial repair and reduces simulated menstrual bleeding in mice with induced adenomyosis

Mao,

Liu,

Guo

2024

American Journal of Obstetrics and Gynecology

View full text Add to dashboard Cite

Immunometabolic profiling of cervicovaginal lavages identifies key signatures associated with adenomyosis

Cited by 4 publications

References 56 publications

Cervicovaginal Metabolome and Tumor Characteristics for Endometrial Cancer Detection and Risk Stratification

Cervicovaginal Metabolome and Tumor Characteristics for Endometrial Cancer Detection and Risk Stratification

Protein biomarkers in cervicovaginal lavages for detection of endometrial cancer

Meclizine improves endometrial repair and reduces simulated menstrual bleeding in mice with induced adenomyosis

Contact Info

Product

Resources

About