scholarly journals An allele on chromosome 5 residing within the ZSWIM6 region distinguishes patients with basal-like human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor

Patients diagnosed with basal-like (also known as basal) subtype breast cancer face a more aggressive disease course and more dismal prognosis than patients diagnosed with luminal A and luminal B breast cancer molecular subtypes (1-4). We mined published microarray data (5, 6) to understand in an unbiased fashion the most distinguishing genetic and transcriptional features of tumors from patients with basal or basal-like subtype breast cancer. We identified a single nucleotide polymorphism, rs6449531 in ZSWIM6 as among the most significant genetic differences in the tumors of patients with basal-like breast cancer. In a separate cohort of patients with basal subtype breast cancer, we observed transcriptome-wide differential expression of a ZSWIM6 transcript. Analysis of patient survival data revealed that ZSWIM6 primary tumor expression was correlated with overall survival in patients with basal subtype breast cancer. Sequence variation in the ZSWIM6 gene may be important in understanding differences in genetic background that favor development of basal subtype human breast cancer.

2022 ◽  
Author(s):  
Shahan Mamoor

Patients diagnosed with basal-like breast cancer face a more aggressive disease course and more dismal prognosis than patients diagnosed with luminal A and luminal B breast cancer molecular subtypes (1-4). We mined published microarray data (5, 6) to understand in an unbiased fashion the most distinguishing transcriptional features of tumors from patients with basal or basal-like subtype breast cancer. We observed transcriptome-wide differential expression of the vascular endothelial growth factor A, VEGFA, when comparing tumors of patients with basal-like breast cancer with that of other PAM50 molecular subtypes. VEGF-A mRNA was present at significantly higher quantities in the tumors of patients with basal-like breast cancer. Analysis of patient survival data revealed that VEGF-A primary tumor expression was correlated with recurrence-free survival, with higher VEGF-A associated with inferior outcomes - in basal-like patients but not in luminal A, luminal B, HER2+, or normal-like patients. High VEGF-A expression appears to distinguish basal-like human breast cancer from the other molecular subtypes.


2022 ◽  
Author(s):  
Shahan Mamoor

Patients diagnosed with basal-like breast cancer face a more aggressive disease course and more dismal prognosis than patients diagnosed with luminal A and luminal B breast cancer molecular subtypes (1-4). We mined published microarray data (5, 6) to understand in an unbiased fashion the most distinguishing transcriptional features of tumors from patients with basal or basal-like subtype breast cancer. We observed transcriptome-wide differential expression of the transcription factor GATA3 when comparing tumors of patients with basal-like breast cancer with that of other PAM50 molecular subtypes. GATA3 mRNA was present at significantly reduced quantities in the tumors of patients with basal-like breast cancer. Analysis of patient survival data revealed that GATA3 primary tumor expression was correlated with distant metastasis-free survival, with low GATA3 expression correlated with inferior survival outcomes. Low GATA3 expression appears to distinguish basal-like human breast cancer from the other molecular subtypes.


2022 ◽  
Author(s):  
Shahan Mamoor

Patients diagnosed with basal-like breast cancer face a more aggressive disease course and more dismal prognosis than patients diagnosed with luminal A and luminal B breast cancer molecular subtypes (1-4). We mined published microarray data (5, 6) to understand in an unbiased fashion the most distinguishing transcriptional features of tumors from patients with basal or basal-like subtype breast cancer. We observed transcriptome-wide differential expression of SRY-box 11, SOX11, when comparing tumors of patients with basal-like breast cancer with that of other PAM50 molecular subtypes. SOX11 mRNA was present at significantly higher quantities in the tumors of patients with basal-like breast cancer. Analysis of patient survival data revealed that SOX11 primary tumor expression was correlated with overall survival, with higher SOX11 associated with inferior outcomes - in basal-like patients but not in luminal A, luminal B, HER2+, or normal-like patients. Elevated SOX11 expression appears to distinguish basal-like human breast cancer from the other molecular subtypes.


2022 ◽  
Author(s):  
Shahan Mamoor

Patients diagnosed with basal-like breast cancer face a more aggressive disease course and more dismal prognosis than patients diagnosed with luminal A and luminal B breast cancer molecular subtypes (1-4). We mined published microarray data (5, 6) to understand in an unbiased fashion the most distinguishing genetic and transcriptional features of tumors from patients with basal or basal-like subtype breast cancer. We identified a single nucleotide polymorphism (rs625223) residing within NEBL (C10orf113) as among the most significant genetic differences in the tumors of patients with basal-like breast cancer. In a separate cohort of patients with basal subtype breast cancer, we observed transcriptome-wide differential tumor expression of a C10orf113 transcript. Analysis of patient survival data revealed that C10orf113 primary tumor expression was correlated with recurrence-free survival and distant metastasis-free survival in patients with basal-like breast cancer, but in a contrary manner. Thus, single nucleotide variants on both chromosome 5 (7) and chromosome 10 are fundamental differences that define the genetic composition of basal-like breast cancer in humans.


2020 ◽  
Author(s):  
Rong Jia ◽  
Zhongxian Li ◽  
Wei Liang ◽  
Yucheng Ji ◽  
Yujie Weng ◽  
...  

Abstract Background Breast cancer subtypes are statistically associated with prognosis. The search for markers of breast tumor heterogeneity and the development of precision medicine for patients are the current focuses of the field. Methods We used a bioinformatic approach to identify key disease-causing genes unique to the luminal A and basal-like subtypes of breast cancer. First, we retrieved gene expression data for luminal A breast cancer, basal-like breast cancer, and normal breast tissue samples from The Cancer Genome Atlas database. The differentially expressed genes unique to the 2 breast cancer subtypes were identified and subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. We constructed protein–protein interaction networks of the differentially expressed genes. Finally, we analyzed the key modules of the networks, which we combined with survival data to identify the unique cancer genes associated with each breast cancer subtype. Results We identified 1,114 differentially expressed genes in luminal A breast cancer and 1,042 differentially expressed genes in basal-like breast cancer, of which the subtypes shared 500. We observed 614 and 542 differentially expressed genes unique to luminal A and basal-like breast cancer, respectively. Through enrichment analyses, protein–protein interaction network analysis, and module mining, we identified 8 key differentially expressed genes unique to each subtype. Analysis of the gene expression data in the context of the survival data revealed that high expression of NMUR1 and NCAM1 in luminal A breast cancer statistically correlated with poor prognosis, whereas the low expression levels of CDC7 , KIF18A , STIL , and CKS2 in basal-like breast cancer statistically correlated with poor prognosis. Conclusions NMUR1 and NCAM1 are novel key disease-causing genes for luminal A breast cancer, and STIL is a novel key disease-causing gene for basal-like breast cancer. These genes are potential targets for clinical treatment.


2021 ◽  
Author(s):  
Shahan Mamoor

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of a readthrough transcript of CCL14 and CCL15, CCL14-CCL15, when comparing primary tumors of the breast to the tissue of origin, the normal breast. CCL14-CCL15 mRNA was present at significantly lower quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of CCL14-CCL15 in primary tumors of the breast was correlated with overall survival in patients with luminal A cancers, demonstrating a relationship between primary tumor expression of a differentially expressed gene and patient survival outcomes influenced by molecular subtype. These data document a potential role for a readthrough chemokine transcript in human breast cancer.


2020 ◽  
Vol 53 (1) ◽  
Author(s):  
Jaehyuk Yang ◽  
Seung Jun Lee ◽  
Yongseok Kwon ◽  
Li Ma ◽  
Jongchan Kim

Abstract Background Basal-like breast cancer (BLBC) or triple-negative breast cancer (TNBC) is an aggressive and highly metastatic subtype of human breast cancer. The present study aimed to elucidate the potential tumor-suppressive function of MATR3, an abundant nuclear protein, in BLBC/TNBC, whose cancer-relevance has not been characterized. Methods We analyzed in vitro tumorigenecity by cell proliferation and soft agar colony formation assays, apoptotic cell death by flow cytometry and Poly (ADP-ribose) polymerase (PARP) cleavage, epithelial-mesenchymal transition (EMT) by checking specific EMT markers with real-time quantitative PCR and in vitro migration and invasion by Boyden Chamber assays. To elucidate the underlying mechanism by which MATR3 functions as a tumor suppressor, we performed Tandem affinity purification followed by mass spectrometry (TAP-MS) and pathway analysis. We also scrutinized MATR3 expression levels in the different subtypes of human breast cancer and the correlation between MATR3 expression and patient survival by bioinformatic analyses of publicly available transcriptome datasets. Results MATR3 suppressed in vitro tumorigenecity, promoted apoptotic cell death and inhibited EMT, migration, and invasion in BLBC/TNBC cells. Various proteins regulating apoptosis were identified as MATR3-binding proteins, and YAP/TAZ pathway was suppressed by MATR3. MATR3 expression was inversely correlated with the aggressive and metastatic nature of breast cancer. Moreover, high expression levels of MATR3 were associated with a good prognosis of breast cancer patients. Conclusions Our data demonstrate that MATR3 functions as a putative tumor suppressor in BLBC/TNBC cells. Also, MATR3 potentially plays a role as a biomarker in predicting chemotherapy-sensitivity and patient survival in breast cancer patients.


2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Kai Fang ◽  
Hu Caixia ◽  
Zhang Xiufen ◽  
Guo Zijian ◽  
Lihua Li

Understanding of prognostic factors and therapeutic targets for breast cancer is imperative for guidance of patient care. We studied 1203 tumour samples from the Gene Expression Omnibus (GEO) to evaluate potential genes related to breast cancer. R software was used to analyse differentially expressed long noncoding RNAs (lncRNAs) in the RNA microarray expression profiles GSE45827 and GSE65216 and to identify a series of differentially expressed lncRNAs associated with human breast cancer. Of these lncRNAs, A2M-AS1, a lncRNA that has not been previously reported, was significantly upregulated in human breast cancer tissues compared with adjacent nontumour tissues. Importantly, A2M-AS1 upregulation was significantly associated with ER-negative, HER2-positive, and basal-like breast cancer and with poor recurrence-free survival and metastasis-free survival in breast cancer patients. After validating these results in 96 collected human breast cancer tissues and 64 paired adjacent noncancerous tissues, we further investigated the roles of A2M-AS1 in human ER-negative and basal-like breast cancer cells. The results revealed that A2M-AS1 significantly promotes human breast cancer cell proliferation, invasion, and migration. Additionally, bioinformatics analysis of genes coexpressed with A2M-AS1 in the context of human breast cancer combined with qRT-PCR and Western blot assays revealed that A2M-AS1 exerts regulatory effects on downstream factors in the cell adhesion molecule pathway, including CD2 and SELL. These results imply that A2M-AS1 might be a promising candidate prognostic factor and therapeutic target for breast cancer.


2012 ◽  
Vol 08 (01) ◽  
pp. 26
Author(s):  
Andrew Y Shuen ◽  
William D Foulkes ◽  
◽  

Breast cancer is a heterogeneous disease. Gene expression profiling has demonstrated the existence of at least five ‘intrinsic’ subtypes: luminal A, luminal B, human epidermal growth factor-2 receptor (HER2), normal-like, and basal-like. While the estrogen receptor (ER), progesterone receptor (PR), and HER2 remain the most important prognostic markers and predictors of response to therapy, interrogating thousands of genetic transcripts more accurately captures the biological complexity and clinical heterogeneity of this disease. Target identification through massively parallel sequencing is likely to bear fruit in the coming years. Attention to basal-like breast cancers has grown substantially due to their generally poor prognosis, lack of targeted therapies, and connection withBRCA1-related cancers. In this article, we discuss the basal-like subgroup with respect to its cellular origins, relationship toBRCA1, and associated epidemiological risk factors.


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