scholarly journals Gene Dosage Analysis on the Single-Cell Transcriptomes Linking Cotranslational Protein Targeting to Metastatic Triple-Negative Breast Cancer

2021 ◽  
Vol 14 (9) ◽  
pp. 918
Author(s):  
Yining Liu ◽  
Min Zhao

Many recent efforts have been put into the association between expression heterogeneity and different cell types and states using single-cell RNA transcriptome analysis. There is only limited understanding of gene dosage effects for the genetic heterogeneity at the single-cell level. By focusing on concordant copy number variation (CNV) and expression, we presented a computational framework to explore dosage effect for aggressive metastatic triple-negative breast cancer (TNBC) at the single-cell level. In practice, we collected CNV and single-cell expression data from the same patients with independent technologies. By focusing on 47,198 consistent copy number gains (CNG) and gene up-regulation from 1145 single cells, ribosome proteins with important roles in protein targeting were enriched. Independent validation in another metastatic TNBC dataset further prioritized signal recognition particle-dependent protein targeting as the top functional module. More interesting, the increased ribosome gene copies in TNBC may associate with their enhanced stemness and metastatic potential. Indeed, the prioritization of a well-upregulated functional module confirmed by high copy numbers at the single-cell level and contributing to patient survival may indicate the possibility of targeted therapy based on ribosome proteins for TNBC.

2016 ◽  
Vol 48 (10) ◽  
pp. 1119-1130 ◽  
Author(s):  
Ruli Gao ◽  
Alexander Davis ◽  
Thomas O McDonald ◽  
Emi Sei ◽  
Xiuqing Shi ◽  
...  

2014 ◽  
Vol 9 (4) ◽  
pp. 749-757 ◽  
Author(s):  
Marta Pestrin ◽  
Francesca Salvianti ◽  
Francesca Galardi ◽  
Francesca De Luca ◽  
Natalie Turner ◽  
...  

Author(s):  
Heae Surng Park ◽  
Min Hye Jang ◽  
Eun Joo Kim ◽  
Hyun Jeong Kim ◽  
Hee Jin Lee ◽  
...  

Author(s):  
AI Fernandez ◽  
G Graham ◽  
B Győrffy ◽  
L Cavalli ◽  
A Mahajan ◽  
...  

2008 ◽  
Vol 47 (6) ◽  
pp. 490-499 ◽  
Author(s):  
Wonshik Han ◽  
Eun-Mi Jung ◽  
Jihyoung Cho ◽  
Jong Won Lee ◽  
Ki-Tae Hwang ◽  
...  

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Milica Nedeljković ◽  
Nikola Tanić ◽  
Tatjana Dramićanin ◽  
Zorka Milovanović ◽  
Snežana Šušnjar ◽  
...  

Summary Background: Triple negative breast cancer (TNBC) is characterized by aggressive clinical course and is unresponsive to anti-HER2 and endocrine therapy. TNBC is difficult to treat and is often lethal. Given the need to find new targets for therapy we explored clinicopathological significance of copy number gain of FGFR1 and c-MYC. Our aim was to determine the impact of FGFR1 and c-MYC copy number gain on clinical course and outcome of TNBC. Methods: FGFR1 and c-MYC gene copy number alterations were evaluated in 78 archive TNBC samples using TaqMan based quantitative real time PCR assays. Results: 50% of samples had increased c-MYC copy number. c-MYC copy number gain was associated with TNBC in contrast to ER positive cancers. Our results showed significant correlation between c-MYC copy number gain and high grade of TNBCs. This suggests that c-MYC copy number could be an useful prognostic marker for TNBC patients. c-MYC copy number gain was associated with high pTNM stage as well as lobular and medullary tumor subtypes. 43% of samples had increased FGFR1 copy number. No correlations between FGFR1 copy number gain and clinicopathological variables were observed. Conclusions: We identified c-MYC copy number gain as a prognostic marker for TNBC. Our results indicate that c- MYC may contribute to TNBC progression. We observed no significant association between c-MYC and/or FGFR1 copy number status and patient survival.


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