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.
Research article
Kelly A. Avery-Kiejda
University of Newcastle
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Triple negative breast cancer (TNBC) is a highly metastatic and aggressive subtype of breast cancer and cases presenting with lymph node involvement have worse outcomes. This study aimed to determine the regions of copy number variation (CNV) associated with lymph node metastasis in TNBC patients.
Methods
CNV analyses were performed in a study cohort of 23 invasive ductal carcinomas (IDC), 12 lymph node metastases (LNmets) and 7 normal adjacent tissues (NAT); as well as in a second cohort containing 70 TNBC IDC samples and the same 7 NATs. CNVs associated genes were analysed using GO-enrichment and Pathway analysis and also integrated with gene expression analysis. The prognostic role for genes showing CNV based change in mRNA expression was determined using Kaplan-Meier (KM) plotter database.
Results
For the IDCs, frequent amplification was evident in chromosomal regions 8q, 1q, 2(p and q), 3q24, 10p and 12p and deletion in 3p, 4 (p and q), 5q, 14q and 17p in contrast to LNmets showing frequent amplification of 4q, 2p, 3q24, 1q, 10p, 12p, 8q, 20p, 21q and 6p and deletion in 1p, 4q (4q21.1, 4q26) and 5q. A total of 686 (441 amplified and 245 deleted) genes were associated with lymph node metastasis. The LNmet-associated genes were highly enriched for “regulation of complement activation”, “regulation of protein activation cascade”, “regulation of humoral immune response”, “oxytocin signalling pathway” and “trail binding” pathways. Moreover, 6/686 LNmet-associated genes showed CNV-based changes in their mRNA expression of which, high expression of ASPM and KIF14 was significantly associated with worse relapse free survival.
Conclusion
This study has identified several CNV regions in TNBC that could play a major role in metastasis to the lymph node.
Keywords
Triple negative breast cancer, Copy number variation, Invasive ductal carcinoma, Lymph node metastasis, amplification, deletion
Figure 1
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Figure 3
Figure 4
Figure 5
This is a list of supplementary files associated with this preprint. Click to download.
- Additionalfile12TableS15S16.xlsx
- Additionalfile11TableS14.xlsx
- Additionalfile10TableS13.xlsx
- Additionalfile9TableS12.xlsx
- Additionalfile8TableS11.xlsx
- Additionalfile7TableS9S10.xlsx
- Additionalfile6TableS8.xlsx
- Additionalfile5TableS7.xlsx
- Additionalfile4TableS6.xlsx
- Table1.pptx
- Additionalfile3TableS5.xlsx
- Additionalfile2TableS4.xlsx
- Additionalfile1TableS1S2S3.xlsx
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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.
Research article
Kelly A. Avery-Kiejda
University of Newcastle
Corresponding Author
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 10 Aug, 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
Triple negative breast cancer (TNBC) is a highly metastatic and aggressive subtype of breast cancer and cases presenting with lymph node involvement have worse outcomes. This study aimed to determine the regions of copy number variation (CNV) associated with lymph node metastasis in TNBC patients.
Methods
CNV analyses were performed in a study cohort of 23 invasive ductal carcinomas (IDC), 12 lymph node metastases (LNmets) and 7 normal adjacent tissues (NAT); as well as in a second cohort containing 70 TNBC IDC samples and the same 7 NATs. CNVs associated genes were analysed using GO-enrichment and Pathway analysis and also integrated with gene expression analysis. The prognostic role for genes showing CNV based change in mRNA expression was determined using Kaplan-Meier (KM) plotter database.
Results
For the IDCs, frequent amplification was evident in chromosomal regions 8q, 1q, 2(p and q), 3q24, 10p and 12p and deletion in 3p, 4 (p and q), 5q, 14q and 17p in contrast to LNmets showing frequent amplification of 4q, 2p, 3q24, 1q, 10p, 12p, 8q, 20p, 21q and 6p and deletion in 1p, 4q (4q21.1, 4q26) and 5q. A total of 686 (441 amplified and 245 deleted) genes were associated with lymph node metastasis. The LNmet-associated genes were highly enriched for “regulation of complement activation”, “regulation of protein activation cascade”, “regulation of humoral immune response”, “oxytocin signalling pathway” and “trail binding” pathways. Moreover, 6/686 LNmet-associated genes showed CNV-based changes in their mRNA expression of which, high expression of ASPM and KIF14 was significantly associated with worse relapse free survival.
Conclusion
This study has identified several CNV regions in TNBC that could play a major role in metastasis to the lymph node.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
This is a list of supplementary files associated with this preprint. Click to download.
- Additionalfile12TableS15S16.xlsx
- Additionalfile11TableS14.xlsx
- Additionalfile10TableS13.xlsx
- Additionalfile9TableS12.xlsx
- Additionalfile8TableS11.xlsx
- Additionalfile7TableS9S10.xlsx
- Additionalfile6TableS8.xlsx
- Additionalfile5TableS7.xlsx
- Additionalfile4TableS6.xlsx
- Table1.pptx
- Additionalfile3TableS5.xlsx
- Additionalfile2TableS4.xlsx
- Additionalfile1TableS1S2S3.xlsx
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