A novel PDX modeling strategy and its application in metabolomics study for malignant pleural mesothelioma

Abstract Background Malignant pleural mesothelioma (MPM) is a rare and aggressive carcinoma located in pleural cavity. Due to lack of effective diagnostic biomarkers and therapeutic targets in MPM, the prognosis is extremely poor. Because of difficulties in sample extraction, and the high rate of mi...

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Autores principales:	Zhongjian Chen, Chenxi Yang, Zhenying Guo, Siyu Song, Yun Gao, Ding Wang, Weimin Mao, Junping Liu
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Patient-derived xenograft Malignant pleural mesothelioma GC-MS Metabolomics Ultrasound-guided biopsy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/d667ec7deb8b4f9ebcd02aef60446ca3
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spelling	oai:doaj.org-article:d667ec7deb8b4f9ebcd02aef60446ca32021-11-21T12:30:24ZA novel PDX modeling strategy and its application in metabolomics study for malignant pleural mesothelioma10.1186/s12885-021-08980-51471-2407https://doaj.org/article/d667ec7deb8b4f9ebcd02aef60446ca32021-11-01T00:00:00Zhttps://doi.org/10.1186/s12885-021-08980-5https://doaj.org/toc/1471-2407Abstract Background Malignant pleural mesothelioma (MPM) is a rare and aggressive carcinoma located in pleural cavity. Due to lack of effective diagnostic biomarkers and therapeutic targets in MPM, the prognosis is extremely poor. Because of difficulties in sample extraction, and the high rate of misdiagnosis, MPM is rarely studied. Therefore, novel modeling methodology is crucially needed to facilitate MPM research. Methods A novel patient-derived xenograft (PDX) modeling strategy was designed, which included preliminary screening of patients with pleural thickening using computerized tomography (CT) scan, further reviewing history of disease and imaging by a senior sonographer as well as histopathological analysis by a senior pathologist, and PDX model construction using ultrasound-guided pleural biopsy from MPM patients. Gas chromatography-mass spectrometry-based metabolomics was further utilized for investigating circulating metabolic features of the PDX models. Univariate and multivariate analysis, and pathway analysis were performed to explore the differential metabolites, enriched metabolism pathways and potential metabolic targets. Results After screening using our strategy, 5 out of 116 patients were confirmed to be MPM, and their specimens were used for modeling. Two PDX models were established successfully. Metabolomics analysis revealed significant metabolic shifts in PDX models, such as dysregulations in amino acid metabolism, TCA cycle and glycolysis, and nucleotide metabolism. Conclusions To sum up, we suggested a novel modeling strategy that may facilitate specimen availability for MM research, and by applying metabolomics in this model, several metabolic features were identified, whereas future studies with large sample size are needed.Zhongjian ChenChenxi YangZhenying GuoSiyu SongYun GaoDing WangWeimin MaoJunping LiuBMCarticlePatient-derived xenograftMalignant pleural mesotheliomaGC-MSMetabolomicsUltrasound-guided biopsyNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBMC Cancer, Vol 21, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Patient-derived xenograft Malignant pleural mesothelioma GC-MS Metabolomics Ultrasound-guided biopsy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Patient-derived xenograft Malignant pleural mesothelioma GC-MS Metabolomics Ultrasound-guided biopsy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Zhongjian Chen Chenxi Yang Zhenying Guo Siyu Song Yun Gao Ding Wang Weimin Mao Junping Liu A novel PDX modeling strategy and its application in metabolomics study for malignant pleural mesothelioma
description	Abstract Background Malignant pleural mesothelioma (MPM) is a rare and aggressive carcinoma located in pleural cavity. Due to lack of effective diagnostic biomarkers and therapeutic targets in MPM, the prognosis is extremely poor. Because of difficulties in sample extraction, and the high rate of misdiagnosis, MPM is rarely studied. Therefore, novel modeling methodology is crucially needed to facilitate MPM research. Methods A novel patient-derived xenograft (PDX) modeling strategy was designed, which included preliminary screening of patients with pleural thickening using computerized tomography (CT) scan, further reviewing history of disease and imaging by a senior sonographer as well as histopathological analysis by a senior pathologist, and PDX model construction using ultrasound-guided pleural biopsy from MPM patients. Gas chromatography-mass spectrometry-based metabolomics was further utilized for investigating circulating metabolic features of the PDX models. Univariate and multivariate analysis, and pathway analysis were performed to explore the differential metabolites, enriched metabolism pathways and potential metabolic targets. Results After screening using our strategy, 5 out of 116 patients were confirmed to be MPM, and their specimens were used for modeling. Two PDX models were established successfully. Metabolomics analysis revealed significant metabolic shifts in PDX models, such as dysregulations in amino acid metabolism, TCA cycle and glycolysis, and nucleotide metabolism. Conclusions To sum up, we suggested a novel modeling strategy that may facilitate specimen availability for MM research, and by applying metabolomics in this model, several metabolic features were identified, whereas future studies with large sample size are needed.
format	article
author	Zhongjian Chen Chenxi Yang Zhenying Guo Siyu Song Yun Gao Ding Wang Weimin Mao Junping Liu
author_facet	Zhongjian Chen Chenxi Yang Zhenying Guo Siyu Song Yun Gao Ding Wang Weimin Mao Junping Liu
author_sort	Zhongjian Chen
title	A novel PDX modeling strategy and its application in metabolomics study for malignant pleural mesothelioma
title_short	A novel PDX modeling strategy and its application in metabolomics study for malignant pleural mesothelioma
title_full	A novel PDX modeling strategy and its application in metabolomics study for malignant pleural mesothelioma
title_fullStr	A novel PDX modeling strategy and its application in metabolomics study for malignant pleural mesothelioma
title_full_unstemmed	A novel PDX modeling strategy and its application in metabolomics study for malignant pleural mesothelioma
title_sort	novel pdx modeling strategy and its application in metabolomics study for malignant pleural mesothelioma
publisher	BMC
publishDate	2021
url	https://doaj.org/article/d667ec7deb8b4f9ebcd02aef60446ca3
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A novel PDX modeling strategy and its application in metabolomics study for malignant pleural mesothelioma

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