Copy Number Variation in Triple Negative Breast Cancer Samples Associated with Lymph Node Metastasis
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.
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Due to technical limitations, table 1 is only available as a download in the Supplemental Files section.
This is a list of supplementary files associated with this preprint. Click to download.
Posted 10 Aug, 2020
Copy Number Variation in Triple Negative Breast Cancer Samples Associated with Lymph Node Metastasis
Posted 10 Aug, 2020
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
Due to technical limitations, table 1 is only available as a download in the Supplemental Files section.