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This study investigated the cervicovaginal environment to clarify metabolic reprogramming in endometrial cancer and to identify metabolite candidates for noninvasive diagnosis and prognostic risk stratification. Cervicovaginal lavages from patients and controls underwent untargeted global metabolomics and multivariate biomarker discovery.",{"@graph":14,"@context":77},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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Risk Stratification  \nGeorgia M. Lorentzen1,2, Paweł Łaniewski3, Haiyan Cui4, Nichole D. Mahnert1,5, Jamal Mourad1,5, Matthew P. Borst1,5, Lyndsay Willmott6, Dana M. Chase6, Denise J. Roe4,7,  \nand Melissa M. Herbst-Kralovetz1,3,4  \n|  |  | A |  | B | S |  | T | R |  | A |  | C | T |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |\n| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |\n|  | Purpose: Endometrial cancer is highly prevalent and lacking noninvasive 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 the understanding of metabolic reprogramming related to endometrial cancer and identify potential biomarker candidates for noninvasive diagnostic and prognostic tests.\u003Cbr>Experimental Design: Cervicovaginal lavages were collected from 192 participants with endometrial cancer (n ¼ 66) and nonmalignant conditions (n ¼ 108), and global untargeted metabolomics was performed. Using the metabolite data (n ¼ 920), we completed a multivariate biomarker discovery analysis.\u003Cbr>Results: We analyzed grade 1/2 endometrioid carcinoma (n ¼ 53) and other endometrial cancer subtypes (n ¼ 13) to identify shared and unique metabolic signatures between the subtypes. When compared to non-malignant conditions, downregulation of\u003Cbr>􀀶 |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | proline (P \u003C 0.0001), tryptophan (P \u003C 0.0001), and glutamate (P \u003C 0.0001) was found among both endometrial cancer groups, relating to key hallmarks of cancer including immune suppression and redox balance. Upregulation (q \u003C 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.\u003Cbr>Conclusions: Our findings provide insights into understanding the endometrial cancer metabolic landscape and improvement in diagnosis. The metabolic dysregulation described in this article linked specific metabolites and pathophysiological mechanisms including cellular proliferation, energy supply, and invasion of neighboring tissues. Furthermore, cervicovaginal metabolite levels related to tumor characteristics, which are used for risk stratification. Overall, development of noninvasive diagnostics can improve both the acceptability and accessibility of diagnosis. |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |\n\nIntroduction  \nEndometrial cancer is a cancer of the lining of the uterus and is the most prevalent gynecologic malignancy in high-income countries (1), with an annual global estimated incidence of 417,000 new cases and 97,000 deaths (2) . Risk factors of endometrial cancer include increased body mass index (BMI), diabetes, older age, early menopause, hypertension, f","cbCaiuQuMHtmqDEC","https://ap.wps.com/l/cbCaiuQuMHtmqDEC","pdf",5209197,15,"English","# Purpose\n# Experimental Design\n# Results\n# Conclusions\n# Introduction","[{\"question\":\"What is the main goal of this study?\",\"answer\":\"To characterize cervicovaginal metabolic changes linked to endometrial cancer and to identify potential biomarker candidates for noninvasive diagnosis and risk stratification.\"},{\"question\":\"How were participants and samples handled?\",\"answer\":\"Cervicovaginal lavages were collected from 192 participants with endometrial cancer and nonmalignant conditions, followed by global untargeted metabolomics.\"},{\"question\":\"Which outcomes did the results focus on?\",\"answer\":\"The study compared metabolic signatures between endometrial cancer subtypes and non-malignant conditions and examined metabolites related to tumor characteristics such as tumor size and myometrial invasion.\"},{\"question\":\"Why are the findings important clinically?\",\"answer\":\"They support development of improved noninvasive diagnostics that may increase acceptability and accessibility while enabling risk stratification based on cervicovaginal metabolite levels.\"}]","Cervicovaginal Metabolome and Tumor Characteristics for Endometrial Cancer Detection and Risk Stratification | PDF",1789997473,38]