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

Abstract 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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Han Zhang, Yijun Wu, Hao Li, Liping Sun, Xiangkai Meng
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Ovarian cancer Differentially expressed genes Prognosis Immune Chemosensitivity Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/846d504b9be74c329e2f28bbafdbb116
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:846d504b9be74c329e2f28bbafdbb116
record_format	dspace
spelling	oai:doaj.org-article:846d504b9be74c329e2f28bbafdbb1162021-11-08T11:13:36ZModel constructions of chemosensitivity and prognosis of high grade serous ovarian cancer based on evaluation of immune microenvironment and immune response10.1186/s12935-021-02295-y1475-2867https://doaj.org/article/846d504b9be74c329e2f28bbafdbb1162021-11-01T00:00:00Zhttps://doi.org/10.1186/s12935-021-02295-yhttps://doaj.org/toc/1475-2867Abstract 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.Han ZhangYijun WuHao LiLiping SunXiangkai MengBMCarticleOvarian cancerDifferentially expressed genesPrognosisImmuneChemosensitivityNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCancer Cell International, Vol 21, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Ovarian cancer Differentially expressed genes Prognosis Immune Chemosensitivity Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
spellingShingle	Ovarian cancer Differentially expressed genes Prognosis Immune Chemosensitivity Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 Han Zhang Yijun Wu Hao Li Liping Sun Xiangkai Meng Model constructions of chemosensitivity and prognosis of high grade serous ovarian cancer based on evaluation of immune microenvironment and immune response
description	Abstract 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.
format	article
author	Han Zhang Yijun Wu Hao Li Liping Sun Xiangkai Meng
author_facet	Han Zhang Yijun Wu Hao Li Liping Sun Xiangkai Meng
author_sort	Han Zhang
title	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_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_sort	model constructions of chemosensitivity and prognosis of high grade serous ovarian cancer based on evaluation of immune microenvironment and immune response
publisher	BMC
publishDate	2021
url	https://doaj.org/article/846d504b9be74c329e2f28bbafdbb116
work_keys_str_mv	AT hanzhang modelconstructionsofchemosensitivityandprognosisofhighgradeserousovariancancerbasedonevaluationofimmunemicroenvironmentandimmuneresponse AT yijunwu modelconstructionsofchemosensitivityandprognosisofhighgradeserousovariancancerbasedonevaluationofimmunemicroenvironmentandimmuneresponse AT haoli modelconstructionsofchemosensitivityandprognosisofhighgradeserousovariancancerbasedonevaluationofimmunemicroenvironmentandimmuneresponse AT lipingsun modelconstructionsofchemosensitivityandprognosisofhighgradeserousovariancancerbasedonevaluationofimmunemicroenvironmentandimmuneresponse AT xiangkaimeng modelconstructionsofchemosensitivityandprognosisofhighgradeserousovariancancerbasedonevaluationofimmunemicroenvironmentandimmuneresponse
_version_	1718442353029545984

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

Ejemplares similares