Single-cell analysis reveals landscape of endometrial cancer response to estrogen and identification of early diagnostic markers.
<h4>Background</h4>The development of endometrial cancer (EC) is closely related to the abnormal activation of the estrogen signaling pathway. Effective diagnostic markers are important for the early detection and treatment of EC.<h4>Method</h4>We downloaded single-cell RNA s...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0301128&type=printable |
| _version_ | 1797242917552652288 |
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| author | Chunli Dong Liyan Zhao Xiongtao Liu Ling Dang Xin Zhang |
| author_facet | Chunli Dong Liyan Zhao Xiongtao Liu Ling Dang Xin Zhang |
| author_sort | Chunli Dong |
| collection | DOAJ |
| description | <h4>Background</h4>The development of endometrial cancer (EC) is closely related to the abnormal activation of the estrogen signaling pathway. Effective diagnostic markers are important for the early detection and treatment of EC.<h4>Method</h4>We downloaded single-cell RNA sequencing (scRNA-seq) and spatial transcriptome (ST) data of EC from public databases. Enrichment scores were calculated for EC cell subpopulations using the "AddModuleScore" function and the AUCell package, respectively. Six predictive models were constructed, including logistic regression (LR), Gaussian naive Bayes (GaussianNB), k-nearest neighbor (KNN), support vector machine (SVM), extreme gradient boosting (XGB), and neural network (NK). Subsequently, receiver-operating characteristics with areas under the curves (AUCs) were used to assess the robustness of the predictive model.<h4>Result</h4>We classified EC cell coaggregation into six cell clusters, of which the epithelial, fibroblast and endothelial cell clusters had higher estrogen signaling pathway activity. We founded the epithelial cell subtype Epi cluster1, the fibroblast cell subtype Fib cluster3, and the endothelial cell subtype Endo cluster3 all showed early activation levels of estrogen response. Based on EC cell subtypes, estrogen-responsive early genes, and genes encoding Stage I and para-cancer differentially expressed proteins in EC patients, a total of 24 early diagnostic markers were identified. The AUCs values of all six classifiers were higher than 0.95, which indicates that the early diagnostic markers we screened have superior robustness across different classification algorithms.<h4>Conclusion</h4>Our study elucidates the potential biological mechanism of EC response to estrogen at single-cell resolution, which provides a new direction for early diagnosis of EC. |
| first_indexed | 2024-04-24T18:46:50Z |
| format | Article |
| id | doaj.art-e3e4da4419f7424f847fb9e5dc8442dd |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-24T18:46:50Z |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-e3e4da4419f7424f847fb9e5dc8442dd2024-03-27T05:32:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01193e030112810.1371/journal.pone.0301128Single-cell analysis reveals landscape of endometrial cancer response to estrogen and identification of early diagnostic markers.Chunli DongLiyan ZhaoXiongtao LiuLing DangXin Zhang<h4>Background</h4>The development of endometrial cancer (EC) is closely related to the abnormal activation of the estrogen signaling pathway. Effective diagnostic markers are important for the early detection and treatment of EC.<h4>Method</h4>We downloaded single-cell RNA sequencing (scRNA-seq) and spatial transcriptome (ST) data of EC from public databases. Enrichment scores were calculated for EC cell subpopulations using the "AddModuleScore" function and the AUCell package, respectively. Six predictive models were constructed, including logistic regression (LR), Gaussian naive Bayes (GaussianNB), k-nearest neighbor (KNN), support vector machine (SVM), extreme gradient boosting (XGB), and neural network (NK). Subsequently, receiver-operating characteristics with areas under the curves (AUCs) were used to assess the robustness of the predictive model.<h4>Result</h4>We classified EC cell coaggregation into six cell clusters, of which the epithelial, fibroblast and endothelial cell clusters had higher estrogen signaling pathway activity. We founded the epithelial cell subtype Epi cluster1, the fibroblast cell subtype Fib cluster3, and the endothelial cell subtype Endo cluster3 all showed early activation levels of estrogen response. Based on EC cell subtypes, estrogen-responsive early genes, and genes encoding Stage I and para-cancer differentially expressed proteins in EC patients, a total of 24 early diagnostic markers were identified. The AUCs values of all six classifiers were higher than 0.95, which indicates that the early diagnostic markers we screened have superior robustness across different classification algorithms.<h4>Conclusion</h4>Our study elucidates the potential biological mechanism of EC response to estrogen at single-cell resolution, which provides a new direction for early diagnosis of EC.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0301128&type=printable |
| spellingShingle | Chunli Dong Liyan Zhao Xiongtao Liu Ling Dang Xin Zhang Single-cell analysis reveals landscape of endometrial cancer response to estrogen and identification of early diagnostic markers. PLoS ONE |
| title | Single-cell analysis reveals landscape of endometrial cancer response to estrogen and identification of early diagnostic markers. |
| title_full | Single-cell analysis reveals landscape of endometrial cancer response to estrogen and identification of early diagnostic markers. |
| title_fullStr | Single-cell analysis reveals landscape of endometrial cancer response to estrogen and identification of early diagnostic markers. |
| title_full_unstemmed | Single-cell analysis reveals landscape of endometrial cancer response to estrogen and identification of early diagnostic markers. |
| title_short | Single-cell analysis reveals landscape of endometrial cancer response to estrogen and identification of early diagnostic markers. |
| title_sort | single cell analysis reveals landscape of endometrial cancer response to estrogen and identification of early diagnostic markers |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0301128&type=printable |
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