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PDXNet portal: patient-derived Xenograft model, data, workflow and tool discovery.

ABSTRACT: We created the PDX Network (PDXNet) portal (https://portal.pdxnetwork.org/) to centralize access to the National Cancer Institute-funded PDXNet consortium resources, to facilitate collaboration among researchers and to make these data easily available for research. The portal includes sections for resources, analysis results, metrics for PDXNet activities, data processing protocols and training materials for processing PDX data. Currently, the portal contains PDXNet model information and data resources from 334 new models across 33 cancer types. Tissue samples of these models were deposited in the NCI's Patient-Derived Model Repository (PDMR) for public access. These models have 2134 associated sequencing files from 873 samples across 308 patients, which are hosted on the Cancer Genomics Cloud powered by Seven Bridges and the NCI Cancer Data Service for long-term storage and access with dbGaP permissions. The portal includes results from freely available, robust, validated and standardized analysis workflows on PDXNet sequencing files and PDMR data (3857 samples from 629 patients across 85 disease types). The PDXNet portal is continuously updated with new data and is of significant utility to the cancer research community as it provides a centralized location for PDXNet resources, which support multi-agent treatment studies, determination of sensitivity and resistance mechanisms, and preclinical trials.

SUBMITTER: Koc S

PROVIDER: S-EPMC9026194 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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PDXNet portal: patient-derived Xenograft model, data, workflow and tool discovery.

Koc Soner S Lloyd Michael W MW Grover Jeffrey W JW Xiao Nan N Seepo Sara S Subramanian Sai Lakshmi SL Ray Manisha M Frech Christian C DiGiovanna John J Webster Phillip P Neuhauser Steven S Srivastava Anuj A Woo Xing Yi XY Sanderson Brian J BJ White Brian B Lott Paul P Dobrolecki Lacey E LE Dowst Heidi H Evrard Yvonne A YA Wallace Tiffany A TA Moscow Jeffrey A JA Doroshow James H JH Mitsiades Nicholas N Kaochar Salma S Pan Chong-Xian CX Chen Moon S MS Carvajal-Carmona Luis L Welm Alana L AL Welm Bryan E BE Lewis Michael T MT Govindan Ramaswamy R Ding Li L Li Shunqiang S Herlyn Meenhard M Davies Michael A MA Roth Jack J Meric-Bernstam Funda F Robinson Peter N PN Bult Carol J CJ Davis-Dusenbery Brandi B Dean Dennis A DA Chuang Jeffrey H JH

NAR cancer 20220422 2

We created the PDX Network (PDXNet) portal (https://portal.pdxnetwork.org/) to centralize access to the National Cancer Institute-funded PDXNet consortium resources, to facilitate collaboration among researchers and to make these data easily available for research. The portal includes sections for resources, analysis results, metrics for PDXNet activities, data processing protocols and training materials for processing PDX data. Currently, the portal contains PDXNet model information and data re ...[more]

PMID: 35475145

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Project description:BackgroundNon-gestational choriocarcinoma (NGC) is a rare subtype of malignant germ cell tumour and there is no consensus on its treatment. The lack of suitable preclinical models for NGC is a challenge in drug discovery research. Patient-derived xenograft (PDX) models recapitulate the tumour microenvironment of the original cancer tissue. Therefore, they have received considerable attention for studies on rare cancer. Here, we aimed to establish a PDX model from a patient with recurrent NGC.MethodsFresh NGC tumour tissue was immediately transplanted into a severely immune-deficient mouse (NOD.Cg-Prkdcscid1l2rgtm1Wjl/SzJ) and maintained for more than three in vivo passages. Subsequently, we evaluated the molecular characteristics of the PDX model using immunohistochemistry, polymerase chain reaction, and RNA sequencing. Moreover, the PDX tumours were transplanted into BALB/c nude mice, and we evaluated their sensitivity for cisplatin and methotrexate.ResultsThe PDX tumour maintained the morphological features of NGC. Moreover, Immunohistochemistry revealed that the human chorionic gonadotropin, cytokeratin 7, and EpCAM expression levels were similar to those in the primary tumour. Furthermore, serum human chorionic gonadotropin levels were elevated in both the primary tumour and the PDX models. Additionally, using PCR analysis with species-specific primers, we confirmed that the PDX tumour contained human genes and was derived from human tissue. Moreover, the gene expression profile of the NGC was compared with that of epithelial ovarian cancer samples and cell lines, and 568 dysregulated genes in the NGC were extracted. The expression of the dysregulated genes in PDX was significantly correlated with that in the primary tumour (R2 = 0.873, P < 0.001). Finally, we demonstrated that the PDX tumour was sensitive to cisplatin and methotrexate; therefore, its clinical response to the agents was similar to that of the primary tumour.ConclusionsWe successfully established a PDX model of NGC, to the best of our knowledge, for the first time. The established PDX retained the molecular and transcriptome characteristics of the primary tumour and can be used to predict drug effects. It may facilitate further research and the development of novel therapeutic agents for NGC.

Dataset Information

PDXNet portal: patient-derived Xenograft model, data, workflow and tool discovery.

Publications

PDXNet portal: patient-derived Xenograft model, data, workflow and tool discovery.

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