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Model constructions of chemosensitivity and prognosis of high grade serous ovarian cancer based on evaluation of immune microenvironment and immune response

BACKGROUND: The prognosis of high grade serous ovarian cancer (HGSOC) patients is closely related to the immune microenvironment and immune response. Based on this, the purpose of this study was to construct a model to predict chemosensitivity and prognosis, and provide novel biomarkers for immunoth...

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Autores principales: Zhang, Han, Wu, Yijun, Li, Hao, Sun, Liping, Meng, Xiangkai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567582/
https://www.ncbi.nlm.nih.gov/pubmed/34736480
http://dx.doi.org/10.1186/s12935-021-02295-y
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author Zhang, Han
Wu, Yijun
Li, Hao
Sun, Liping
Meng, Xiangkai
author_facet Zhang, Han
Wu, Yijun
Li, Hao
Sun, Liping
Meng, Xiangkai
author_sort Zhang, Han
collection PubMed
description BACKGROUND: The prognosis of high grade serous ovarian cancer (HGSOC) patients is closely related to the immune microenvironment and immune response. Based on this, the purpose of this study was to construct a model to predict chemosensitivity and prognosis, and provide novel biomarkers for immunotherapy and prognosis evaluation of HGSOC. METHODS: GSE40595 (38 samples), GSE18520 (63 samples), GSE26712 (195 samples), TCGA (321 samples) and GTEx (88 samples) were integrated to screen differential expressed genes (DEGs) of HGSOC. The prognosis related DEGs (DEPGs) were screened through overall survival analysis. The DEGs-encoded protein–protein interaction network was constructed and hub genes of DEPGs (DEPHGs) were generated by STRING. Immune characteristics of the samples were judged by ssGSEA, ESTIMATE and CYBERSORT. TIMER was used to analyze the relationship between DEPHGs and tumor-infiltrating immunocytes, as well as the immune checkpoint genes, finally immune-related DEPHGs (IDEPHGs) were determined, and whose expression in 12 pairs of HGSOC tissues and tumor-adjacent tissues were analyzed by histological verification. Furthermore, the chemosensitivity genes in IDEPHGs were screened according to GSE15622 (n = 65). Finally, two prediction models of paclitaxel sensitivity score (PTX score) and carboplatin sensitivity score (CBP score) were constructed by lasso algorithm. The area under curve was calculated to estimate the accuracy of candidate gene models in evaluating chemotherapy sensitivity. RESULTS: 491 DEGs were screened and 37 DEGs were identified as DEPGs, and 11 DEPHGs were further identified. Among them, CXCL13, IDO1, PI3, SPP1 and TRIM22 were screened as IDEPHGs and verified in the human tissues. Further analysis showed that IDO1, PI3 and TRIM22 could independently affect the chemotherapy sensitivity of HGSOC patients. The PTX score was significantly better than TRIM22, PI3, SPP1, IDO1 and CXCL13 in predicting paclitaxel sensitivity, so was CBP score in predicting carboplatin sensitivity. What’s more, both of the HGSOC patients with high PTX score or high CBP score had longer survival time. CONCLUSIONS: Five IDEPHGs identified through comprehensive bioinformatics analysis were closely related with the prognosis, immune microenvironment and chemotherapy sensitivity of HGSOC. Two prediction models based on IDEPHGs might have potential application of chemotherapy sensitivity and prognosis for patients with HGSOC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02295-y.
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spelling pubmed-85675822021-11-04 Model constructions of chemosensitivity and prognosis of high grade serous ovarian cancer based on evaluation of immune microenvironment and immune response Zhang, Han Wu, Yijun Li, Hao Sun, Liping Meng, Xiangkai Cancer Cell Int Primary Research BACKGROUND: The prognosis of high grade serous ovarian cancer (HGSOC) patients is closely related to the immune microenvironment and immune response. Based on this, the purpose of this study was to construct a model to predict chemosensitivity and prognosis, and provide novel biomarkers for immunotherapy and prognosis evaluation of HGSOC. METHODS: GSE40595 (38 samples), GSE18520 (63 samples), GSE26712 (195 samples), TCGA (321 samples) and GTEx (88 samples) were integrated to screen differential expressed genes (DEGs) of HGSOC. The prognosis related DEGs (DEPGs) were screened through overall survival analysis. The DEGs-encoded protein–protein interaction network was constructed and hub genes of DEPGs (DEPHGs) were generated by STRING. Immune characteristics of the samples were judged by ssGSEA, ESTIMATE and CYBERSORT. TIMER was used to analyze the relationship between DEPHGs and tumor-infiltrating immunocytes, as well as the immune checkpoint genes, finally immune-related DEPHGs (IDEPHGs) were determined, and whose expression in 12 pairs of HGSOC tissues and tumor-adjacent tissues were analyzed by histological verification. Furthermore, the chemosensitivity genes in IDEPHGs were screened according to GSE15622 (n = 65). Finally, two prediction models of paclitaxel sensitivity score (PTX score) and carboplatin sensitivity score (CBP score) were constructed by lasso algorithm. The area under curve was calculated to estimate the accuracy of candidate gene models in evaluating chemotherapy sensitivity. RESULTS: 491 DEGs were screened and 37 DEGs were identified as DEPGs, and 11 DEPHGs were further identified. Among them, CXCL13, IDO1, PI3, SPP1 and TRIM22 were screened as IDEPHGs and verified in the human tissues. Further analysis showed that IDO1, PI3 and TRIM22 could independently affect the chemotherapy sensitivity of HGSOC patients. The PTX score was significantly better than TRIM22, PI3, SPP1, IDO1 and CXCL13 in predicting paclitaxel sensitivity, so was CBP score in predicting carboplatin sensitivity. What’s more, both of the HGSOC patients with high PTX score or high CBP score had longer survival time. CONCLUSIONS: Five IDEPHGs identified through comprehensive bioinformatics analysis were closely related with the prognosis, immune microenvironment and chemotherapy sensitivity of HGSOC. Two prediction models based on IDEPHGs might have potential application of chemotherapy sensitivity and prognosis for patients with HGSOC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02295-y. BioMed Central 2021-11-04 /pmc/articles/PMC8567582/ /pubmed/34736480 http://dx.doi.org/10.1186/s12935-021-02295-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Primary Research
Zhang, Han
Wu, Yijun
Li, Hao
Sun, Liping
Meng, Xiangkai
Model constructions of chemosensitivity and prognosis of high grade serous ovarian cancer based on evaluation of immune microenvironment and immune response
title Model constructions of chemosensitivity and prognosis of high grade serous ovarian cancer based on evaluation of immune microenvironment and immune response
title_full Model constructions of chemosensitivity and prognosis of high grade serous ovarian cancer based on evaluation of immune microenvironment and immune response
title_fullStr Model constructions of chemosensitivity and prognosis of high grade serous ovarian cancer based on evaluation of immune microenvironment and immune response
title_full_unstemmed Model constructions of chemosensitivity and prognosis of high grade serous ovarian cancer based on evaluation of immune microenvironment and immune response
title_short Model constructions of chemosensitivity and prognosis of high grade serous ovarian cancer based on evaluation of immune microenvironment and immune response
title_sort model constructions of chemosensitivity and prognosis of high grade serous ovarian cancer based on evaluation of immune microenvironment and immune response
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567582/
https://www.ncbi.nlm.nih.gov/pubmed/34736480
http://dx.doi.org/10.1186/s12935-021-02295-y
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