This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Primary research
Metastasis progression through the interplay between the immune system and Epithelial-Mesenchymal-Transition in circulating breast tumor cells
Sadegh Azimzadeh Jamalkandi
University of Tehran
Corresponding Author
ORCiD: https://orcid.org/0000-0003-3403-3700
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Circulating tumor cells (CTCs) are the critical initiator of systemic dissemination of cancer, contributing to distant metastasis formation. The metastatic cascades rely on the fundamental roles of different types of CTCs. In which the dual immune responses and epithelial-mesenchymal-transition (EMT) are of two metastasis-driving phenomena and require more molecular assessments.
Methods
In this study, we investigated the transcriptomic modular pattern of single/cluster circulating tumor cells (CTCs). The co-expression analysis implemented, and we could detect two metastatic subnetworks indicating the immune responses and EMT in CTCs. Furthermore, a directed subnetwork identified in the KEGG database. The metastatic potential of subnetworks assessed and validated by classification methods on primary tumors. And, we could fit risk models to distant-metastasis survival of patients.
Results
Our results show the crosstalk among EMT, immune system, menstrual cycles, and stemness in CTCs. In which, fluctuation of menstrual cycles (hormone-related signals) is a new detected pathway in CTCs in breast cancer. The immune SVM model showed high metastatic potential in classifying patients metastatic/non-metastatic groups (accuracy, sensitivity, and specificity scores are 78%). The distant-metastasis free survival model could be used to stratify patients into low, medium, and high-risk groups. Finally, PTCRA, F13A1, LAT, ICAM2, and SNRPC are novel detected biomarkers in breast cancer.
Conclusion
In conclusion, different types of CTCs, including cluster/single cells, are metastasis-leading elements in breast cancer. In which, individual assessment of their intrinsic biological properties may assist elucidating metastasis-related mechanisms. These findings may apply to develop superior treatments in the clinic.
Keywords
breast cancer, single CTC, cluster CTC, metastasis, co-expression, EMT, immune response
Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 08 Jun, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cancer Biology
Learn more about our company.
This is a preprint. It has not completed peer review.
Primary research
Metastasis progression through the interplay between the immune system and Epithelial-Mesenchymal-Transition in circulating breast tumor cells
Sadegh Azimzadeh Jamalkandi
University of Tehran
Corresponding Author
ORCiD: https://orcid.org/0000-0003-3403-3700
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 08 Jun, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cancer Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Circulating tumor cells (CTCs) are the critical initiator of systemic dissemination of cancer, contributing to distant metastasis formation. The metastatic cascades rely on the fundamental roles of different types of CTCs. In which the dual immune responses and epithelial-mesenchymal-transition (EMT) are of two metastasis-driving phenomena and require more molecular assessments.
Methods
In this study, we investigated the transcriptomic modular pattern of single/cluster circulating tumor cells (CTCs). The co-expression analysis implemented, and we could detect two metastatic subnetworks indicating the immune responses and EMT in CTCs. Furthermore, a directed subnetwork identified in the KEGG database. The metastatic potential of subnetworks assessed and validated by classification methods on primary tumors. And, we could fit risk models to distant-metastasis survival of patients.
Results
Our results show the crosstalk among EMT, immune system, menstrual cycles, and stemness in CTCs. In which, fluctuation of menstrual cycles (hormone-related signals) is a new detected pathway in CTCs in breast cancer. The immune SVM model showed high metastatic potential in classifying patients metastatic/non-metastatic groups (accuracy, sensitivity, and specificity scores are 78%). The distant-metastasis free survival model could be used to stratify patients into low, medium, and high-risk groups. Finally, PTCRA, F13A1, LAT, ICAM2, and SNRPC are novel detected biomarkers in breast cancer.
Conclusion
In conclusion, different types of CTCs, including cluster/single cells, are metastasis-leading elements in breast cancer. In which, individual assessment of their intrinsic biological properties may assist elucidating metastasis-related mechanisms. These findings may apply to develop superior treatments in the clinic.
Figure 4