Abstract 822
Background
Cancer cells can exploit normally dormant embryonic stem cell pathways to promote cancer progression. Studying embryonic signaling pathways in aggressive cancers has led to the discovery of the re-expression of the embryonic protein Nodal. It maintains pluripotency and cell plasticity of human embryonic stem cells. In many cancers Nodal signalling promotes tumor growth and metastasis. The objective of this study is to investigate the role of Nodal as a potential biomarker of ovarian cancer (OC) progression and resistance to chemotherapy.
Methods
We applied bioinformatics approach and RNA sequencing to investigate the impact of Nodal on biological processes in OC cells and disease outcome in OC patients (TCGA data). In vitro assays designed to assess cancer stem cell phenotypes and chemoresistance in OC cells wherein Nodal was overexpressed, or knocked out with CRISP/Cas9 genome editing were conducted. We performed IHC staining of Nodal in tissue microarrays of high-grade serous OCs (HGSOC) to evaluate prognostic significance of Nodal. HGSOC samples were obtained from Ovarian Cancer in Alberta and British Columbia study (OVAL-BC) cohort of OC patients (563 HGSOC samples).
Results
RNA seq data showed that Nodal induces transcriptional reprogramming in OC cells via altering immune response, metabolism and drug resistance gene expression. In vitro, we showed that Nodal is a stress response gene which expression and protein increased in OC cells after treatment with cisplatin/carboplatin and retained for 96h after drug withdrawal. OC cells overexpressing Nodal characterized by increased resistance to cytostatic drugs, tumorigenicity and cell plasticity (partial EMT and stem cell-like phenotype). Analysis of TCGA microarray data and IHC staining of tissue microarrays of HGSOCs determined that Nodal predicts poor overall and progression-free survival in HGSOC patients.
Conclusions
Nodal predicts poor survival in HGSOC patients and likely drives tumorigenic potential and resistance to platinum in OC cells by promoting cancer stem cell plasticity and upregulating target genes involved in immune response, drug resistance and metabolism, and may hold promise as a therapeutic target to prevent disease recurrence following chemotherapy.
Clinical trial identification
Legal entity responsible for the study
Lynne Postovit.
Funding
CIHR.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5877 - TCR beta chain convergence defines the tumor infiltrating T cell repertoire of melanoma and non-small cell lung carcinoma.
Presenter: Timothy Looney
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
3212 - PI3K inhibition and modulation of immune and tumor microenvironment markers by copanlisib in patients with non-Hodgkin's lymphoma or advanced solid tumors
Presenter: Ahmad Awada
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
3574 - Pan-squamous genomic profiling stratified by anatomic tumor site and viral association
Presenter: Meagan Montesion
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
4113 - Toward the Standardization of Bioinformatics Methods for the Accurate Assessment of Tumor Mutational Burden (TMB)
Presenter: Han Chang
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
4468 - Prediction of primary resistance to anti-PD1 therapy (APD1) in 2nd line NSCLC
Presenter: Egbert Smit
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
4570 - Immunomodulatory germline variation impacts the development of multiple primary melanoma (MPM).
Presenter: Robert Ferguson
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
1169 - Leukocyte telomere length and recurrence risk after EGFR-TKIs therapy in patients with advanced lung adenocarcinoma
Presenter: Ming Yang
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
1707 - Gene embedding: a novel machine learning approach to identify gene candidates related to immunotherapy responsiveness
Presenter: Chi Tung Choy
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
2123 - Common and rare DPYD variants are predictive for 5FU/capecitabine (5FU) toxicity: The MRC COIN and COIN-B trials
Presenter: Ayman Madi
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5671 - The landscape of NTRK fusions in Chinese solid tumor patients
Presenter: Qi Ling
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract