Proteomic and functional characterization of intra-tumor heterogeneity in human endometrial cancer

Jamaluddin, M Fairuz B; Ko, Yi-An; Ghosh, Arnab; Syed, Shafiq M.; Ius, Yvette; O’Sullivan, Rory; Netherton, Jacob; Baker, Mark A.; Nahar, Pravin; Jaaback, Kenneth; Tanwar, Pradeep S.

doi:10.1016/j.xcrm.2022.100738

Cited by 20 publications

(17 citation statements)

References 86 publications

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“…We found that there was significant heterogeneity in survival of explants using the PDE model outlined in this study which resulted in fewer patients being included in the final analysis, and which made interpreting results difficult. The variable explant viability was likely due to a combination of sampling and handling techniques, the low grade and stage of the tumours, as well as tumour heterogeneity, which has been noted previously with organoid viability [ 29 ]. For example, tumour samples were taken fresh at the time of hysterectomy.…”

Section: Discussionmentioning

confidence: 99%

Development of a long term, ex vivo, patient-derived explant model of endometrial cancer

van der Woude,

Phan,

Kenwright

et al. 2024

PLoS ONE

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Incidence of endometrial cancer (EC) is rising in the developed world. The current standard of care, hysterectomy, is often infeasible for younger patients and those with high body mass index. There are limited non-surgical treatment options and a lack of biologically relevant research models to investigate novel alternatives to surgery for EC. The aim of the present study was to develop a long-term, patient-derived explant (PDE) model of early-stage EC and demonstrate its use for investigating predictive biomarkers for a current non-surgical treatment option, the levonorgestrel intra-uterine system (LNG-IUS). Fresh tumour specimens were obtained from patients with early-stage endometrioid EC. Tumours were cut into explants, cultured on media-soaked gelatin sponges for up to 21 days and treated with LNG. Formalin-fixed, paraffin embedded (FFPE) blocks were generated for each explant after 21 days in culture. Tumour architecture and integrity were assessed by haematoxylin and eosin (H&E) and immunohistochemistry (IHC). IHC was additionally performed for the expression of five candidate biomarkers of LNG resistance. The developed ex vivo PDE model is capable of culturing explants from early-stage EC tumours long-term (21 Days). This model can complement existing models and may serve as a tool to validate results obtained in higher-throughput in vitro studies. Our study provides the foundation to validate the extent to which EC PDEs reflect patient response in future research.

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Section: Discussionmentioning

confidence: 99%

Development of a long term, ex vivo, patient-derived explant model of endometrial cancer

van der Woude,

Phan,

Kenwright

et al. 2024

PLoS ONE

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“…Organoids are used as in vitro culture models for studying endometrial cancer [ 121 ]. Endometrial cancer organoids have successfully recapitulated tumor histology and morphology [ 122 ]. In these organoid culture systems, the characteristics of the tumor genome from patients are fully preserved, which allows for long-term stability and precise fidelity of in vivo transplantation experiments [ 123 ].…”

Section: Application Of Bioengineering Technology In Endometrial Dise...mentioning

confidence: 99%

Bioengineering approaches for the endometrial research and application

Dai,

Liang,

Guo

et al. 2024

Materials Today Bio

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“…The heterogeneity of endometrial cancer is considered to be one of the pivotal factors associated with the failure of targeted therapies. To explore this issue, Jamaluddin et al (2022) performed a SWATH‐MS analysis of 63 tumor biopsies derived from 20 people suffering from endometrial cancer and found that EWSR1 was the most upregulated in endometrial cancer. In addition, they found that TMSB4X might be a novel treatment target for endometrial cancer, particularly in patients with premenopausal endometrial cancer.…”

Section: Application Of the Lfq Proteomics Technology For Malignant T...mentioning

confidence: 99%

Advances in the application of label‐free quantitative proteomics techniques in malignancy research

Meng

Liu

Guan

2023

Biomedical Chromatography

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Proteomics is the scientific discipline that deals with the protein composition of cells, tissues, and organisms and their patterns of change. It is considered an invaluable tool for tackling many challenges faced in medicine and biology. Among the available approaches, label‐free quantitative proteomics techniques are extensively used to study malignant tumors due to their low cost, simple operation, and short cycle time. Therefore, it provides a novel approach to explore the pathogenesis, diagnostic markers, and targeted drugs of malignant tumors. Here, we summarize the research progress and potential of label‐free quantitative proteomics and discuss the application of such techniques in the research on malignancies.

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Proteomic and functional characterization of intra-tumor heterogeneity in human endometrial cancer

Cited by 20 publications

References 86 publications

Development of a long term, ex vivo, patient-derived explant model of endometrial cancer

Development of a long term, ex vivo, patient-derived explant model of endometrial cancer

Bioengineering approaches for the endometrial research and application

Advances in the application of label‐free quantitative proteomics techniques in malignancy research

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