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Unique proteome signature of post-chemotherapy ovarian cancer ascites-derived tumor cells

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posted on 05.08.2021, 07:48 by N Ahmed, David GreeningDavid Greening, C Samardzija, RM Escalona, Maoshan Chen, JK Findlay, G Kannourakis
Eighty % of ovarian cancer patients diagnosed at an advanced-stage have complete remission after initial surgery and chemotherapy. However, most patients die within <5 years due to episodes of recurrences resulting from the growth of residual chemoresistant cells. In an effort to identify mechanisms associated with chemoresistance and recurrence, we compared the expression of proteins in ascites-derived tumor cells isolated from advanced-stage ovarian cancer patients obtained at diagnosis (chemonaive, CN) and after chemotherapy treatments (chemoresistant/at recurrence, CR) by using in-depth, high-resolution label-free quantitative proteomic profiling. A total of 2,999 proteins were identified. Using a stringent selection criterion to define only significantly differentially expressed proteins, we report identification of 353 proteins. There were significant differences in proteins encoding for immune surveillance, DNA repair mechanisms, cytoskeleton rearrangement, cell-cell adhesion, cell cycle pathways, cellular transport, and proteins involved with glycine/proline/arginine synthesis in tumor cells isolated from CR relative to CN patients. Pathway analyses revealed enrichment of metabolic pathways, DNA repair mechanisms and energy metabolism pathways in CR tumor cells. In conclusion, this is the first proteomics study to comprehensively analyze ascites-derived tumor cells from CN and CR ovarian cancer patients.

Funding

This work was supported by the funds received from Ovarian Cancer Research Foundation, Australia to NA. CS is a recipient of the Australian Postgraduate Award. NA is supported by June Wilson Will Trust, BJT Legal, Fiona Elsey Cancer Research Institute, Ballarat, Australia. DG is supported by the LIMS Molecular Biology Stone Fellowship, La Trobe University Research Focus Area Leadership Grant, and La Trobe University Start-up Fund. RE was supported by the funds obtained from Marsha Rivkin Centre for Ovarian Cancer Research to NA. MC is supported by a La Trobe University Postgraduate Scholarship. This work was made possible through the Victorian State Government Operational Infrastructure Support to the Hudson Institute of Medical Research. We acknowledge the La Trobe University-Comprehensive Proteomics Platform for providing infrastructure and expertise for Protein Identification & Quantification.

History

Publication Date

29/07/2016

Journal

Scientific Reports

Volume

6

Issue

1

Article Number

30061

Pagination

13p.

Publisher

Springer Nature

ISSN

2045-2322

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