Protein biomarkers in cervicovaginal lavages for detection of endometrial cancer
Abstract 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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Biomarker Research |
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| Online Access: | https://doi.org/10.1186/s40364-022-00438-5 |
| _version_ | 1811207840025542656 |
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| author | Paweł Łaniewski Haiyan Cui Nichole D. Mahnert Jamal Mourad Matthew P. Borst Lyndsay Willmott Dana M. Chase Denise J. Roe Melissa M. Herbst-Kralovetz |
| author_facet | Paweł Łaniewski Haiyan Cui Nichole D. Mahnert Jamal Mourad Matthew P. Borst Lyndsay Willmott Dana M. Chase Denise J. Roe Melissa M. Herbst-Kralovetz |
| author_sort | Paweł Łaniewski |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-12T04:11:39Z |
| format | Article |
| id | doaj.art-179b7a19cdf2418c95fcae0d9a6dea15 |
| institution | Directory Open Access Journal |
| issn | 2050-7771 |
| language | English |
| last_indexed | 2024-04-12T04:11:39Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Biomarker Research |
| spelling | doaj.art-179b7a19cdf2418c95fcae0d9a6dea152022-12-22T03:48:29ZengBMCBiomarker Research2050-77712022-12-0110111510.1186/s40364-022-00438-5Protein biomarkers in cervicovaginal lavages for detection of endometrial cancerPaweł Łaniewski0Haiyan Cui1Nichole D. Mahnert2Jamal Mourad3Matthew P. Borst4Lyndsay Willmott5Dana M. Chase6Denise J. Roe7Melissa M. Herbst-Kralovetz8College of Medicine – Phoenix, University of ArizonaUA Cancer Center, University of ArizonaCollege of Medicine – Phoenix, University of ArizonaCollege of Medicine – Phoenix, University of ArizonaCollege of Medicine – Phoenix, University of ArizonaArizona Center for Cancer CareArizona Center for Cancer CareUA Cancer Center, University of ArizonaCollege of Medicine – Phoenix, University of ArizonaAbstract 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.https://doi.org/10.1186/s40364-022-00438-5Cervicovaginal microenvironmentEndometrial cancerMinimally to non-invasive diagnosticProtein biomarkerUterine cancerWomen’s health |
| spellingShingle | Paweł Łaniewski Haiyan Cui Nichole D. Mahnert Jamal Mourad Matthew P. Borst Lyndsay Willmott Dana M. Chase Denise J. Roe Melissa M. Herbst-Kralovetz Protein biomarkers in cervicovaginal lavages for detection of endometrial cancer Biomarker Research Cervicovaginal microenvironment Endometrial cancer Minimally to non-invasive diagnostic Protein biomarker Uterine cancer Women’s health |
| title | Protein biomarkers in cervicovaginal lavages for detection of endometrial cancer |
| title_full | Protein biomarkers in cervicovaginal lavages for detection of endometrial cancer |
| title_fullStr | Protein biomarkers in cervicovaginal lavages for detection of endometrial cancer |
| title_full_unstemmed | Protein biomarkers in cervicovaginal lavages for detection of endometrial cancer |
| title_short | Protein biomarkers in cervicovaginal lavages for detection of endometrial cancer |
| title_sort | protein biomarkers in cervicovaginal lavages for detection of endometrial cancer |
| topic | Cervicovaginal microenvironment Endometrial cancer Minimally to non-invasive diagnostic Protein biomarker Uterine cancer Women’s health |
| url | https://doi.org/10.1186/s40364-022-00438-5 |
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