scholarly journals Fli1 is differentially expressed in brain metastatic breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor

Brain metastases affect up to 34% of breast cancer patients treated with trastuzumab (1). Limited treatment options are available for clinical control of brain metastatic breast cancer (2-4). We mined published microarray data (5, 6) to identify genes associated with metastasis to the brain in human breast cancer. This unbiased, global gene expression analysis identified Fli1 as a transcriptional feature of brain metastasis in patients with breast cancer. Fli1 may be of relevance to any one of numerous processes involved in metastasis of breast cancers to the brain, including the generation of tumor clones with sufficient oncogenic potential to colonize the brain.

2020 ◽  
Author(s):  
Shahan Mamoor

Brain metastases affect up to 34% of breast cancer patients treated with trastuzumab (1). Limited treatment options are available for clinical control of brain metastatic breast cancer (2-4). We mined published microarray data (5, 6) to identify genes associated with metastasis to the brain in human breast cancer. This unbiased, global gene expression analysis identified differential expression of aldolase B, encoded by the gene Aldob, an enzyme functioning in the metabolism of fructose (7, 8), as a transcriptional feature of brain metastasis in patients with breast cancer. Aldolase B may be of relevance to processes underlying metastasis to the brain in human metastatic breast cancer.


2020 ◽  
Author(s):  
Shahan Mamoor

Brain metastases affect up to 34% of breast cancer patients treated with trastuzumab (1). Limited treatment options are available for clinical control of brain metastatic breast cancer (2-4). We mined published microarray data (5, 6) to identify genes associated with metastasis to the brain in human breast cancer. This unbiased, global gene expression analysis identified differential expression of the vitamin D (1α,25(OH)2D3) receptor, encoded by VDR, as a transcriptional feature of brain metastasis in patients with breast cancer. Primary tumor expression of VDR was significantly correlated with overall survival in patients with breast cancer. VDR may be of relevance to processes underlying metastasis to the brain in human metastatic breast cancer.


2020 ◽  
Author(s):  
Shahan Mamoor

Brain metastases affect up to 34% of breast cancer patients treated with trastuzumab (1). Limited treatment options are available for clinical control of brain metastatic breast cancer (2-4). We mined published microarray data (5, 6) to identify genes associated with metastasis to the brain in human breast cancer. This unbiased, global gene expression analysis identified differential expression of CD300LG as a transcriptional feature of brain metastasis in patients with breast cancer. Messenger RNA for CD300LG was present at significantly lower quantities in the brain metastatic tissues of patients with metastatic breast cancer. Additional microarray analysis revealed that CD300LG was also among the genes whose expression, transcriptome-wide, was most significantly different in primary tumors of the breast when compared to normal breast tissues. CD300LG is part of the transcriptional signature of human metastatic breast cancer.


2020 ◽  
Author(s):  
Shahan Mamoor

Breast cancer patients diagnosed with metastasis to the brain (1-3) are presented limited treatment options (4, 5). We mined published microarray data (6, 7) to discover genes associated with brain metastasis in human breast cancer at the transcriptome-level and in an unbiased fashion. We describe here the differential expression of the long intergenic non-coding RNA LINC00968 in the brain metastatic tissues and primary tumors of women with breast cancer. LINC00968 transcript was present at significantly reduced quantities at in brain metastases and in primary tumors of the breast as compared to untransformed breast tissues. Molecular functions and down-regulation of LINC00968, a non-coding RNA that has not previously been described in relation to central nervous system metastasis in human breast cancer represents a feature of the transcriptional fingerprint of brain metastatic breast cancer in humans and may be relevant to pathways underlying invasion and colonization of the brain.


2019 ◽  
Author(s):  
Yihang Qi ◽  
Xiangyi Kong ◽  
Xiangyu Wang ◽  
Jie Zhai ◽  
Yi Fang ◽  
...  

Abstract Background. Given that no approved targeted agents for metastatic triple-negative breast cancer (mTNBC) and no opportunity of surgery for metastatic breast cancer (MBC), new treatment options are urgently to be discovered. The anti-PD-1/PD-L1 immunotherapy may be effective, and what we should be aware of is the response rate and adverse events. Methods. The PUBMED, EMBASE, Cochrane and www.clinicaltrials.gov databases were searched to find potential studies using the following strategies: anti-PD-1/PD-L1; metastatic; breast cancer. R© package Meta was used to pool incidence. Results. Six studies including 586 advanced breast cancer patients treated with anti-PD-1/PD-L1 agents were included in this meta-analysis. The anti-PD-1/PD-L1 agents include pembrolizumab, atezolizumab and avelumab. Among these patients, CR was 1.26%, PR was 7.65%, ORR was 9.85% and DCR was 18.33%. We also found that the response rate was closely associated with the expression of PD-L1 biomarker (PD-L1+ vs PD-L1-): the CR was 2.71% vs 0.00%; the PR was 9.93% vs 2.69%; the ORR was 10.62% vs 3.07%; the DCR was 17.95% vs 4.71%. 1-year overall survival rate and 6-months progression-free survival rate were 43.34% and 17.24%. Respectively, the overall incidence of AEs was 64.18% in any grade and 12.94% in severe grade. The incidence of irAEs was 14.75%. Besides, the incidence of discontinue and death due to treatment-related AEs was about 3.06% and 0.31% respectively. When the detailed AEs were analyzed, most treatment-related AEs of any grade were arthraigia, asthenia, decreased appetite; most common treatment-related AEs of severe grade were anemia, autoimmune hepatitis, diarrhea; the most common irAEs were hypothyroidism , followed by hyperthyroidism, pneumonitis and infusion-related reaction. Conclusions. Anti-PD-1/PD-L1 monotherapy showed a manageable safety profile and had a durable anti-tumor clinical activity in a subset of patients with mTNBC or MBC. PD-L1 expression may be correlated to a higher probability of clinical response.


2020 ◽  
Author(s):  
Shahan Mamoor

One study has reported a 34% incidence of central nervous system metastases, including metastasis to the brain, in breast cancer patients treated with trastuzumab (1). We mined published microarray data (2, 3) to discover genes associated with brain metastasis in breast cancer. We identified significant differential expression of the mitochondrial complex II subunit succinate dehydrogenase B, encoded by SDHB (4, 5), in the brain metastases of patients with metastatic breast cancer. SDHB may be relevant to the biology underlying colonization of the brain with metastatic breast cancer clones.


2020 ◽  
Author(s):  
Shahan Mamoor

One study reported the incidence of central nervous system metastases in breast cancer patients treated with trastuzumab as 34% (1). We mined published microarray data (2, 3) to discover genes associated with brain metastasis in breast cancer. We identified significant differential expression of glycoprotein M6A, encoded by GPM6A (4, 5), in the brain metastases of patients with metastatic breast cancer. GPM6A may be relevant to the biology underlying colonization of the brain with metastatic breast cancer clones.


2020 ◽  
Author(s):  
Shahan Mamoor

One study reported the incidence of central nervous system metastases in breast cancer patients treated with trastuzumab as 34% (1). We mined published microarray data (2, 3) to discover genes associated with brain metastasis in breast cancer. We identified significant differential expression of the 17β-hydroxysteroid dehydrogenase type 4, HSD17B4 (4-6), in patients with breast cancer. HSD17B4 may be relevant to the biology underlying colonization of the brain with metastatic breast cancer clones.


2020 ◽  
Author(s):  
Shahan Mamoor

Breast cancer patients diagnosed with metastasis to the brain (1-3) are presented limited treatment options (4, 5). We mined published microarray data (6, 7) to discover genes associated with brain metastasis in human breast cancer, and identified differential expression of RNF186 when comparing brain metastatic tissues to primary tumors of the breast. RNF186 was expressed at significantly lower levels in metastasis to the brain as compared to primary tumors. Molecular functions and down-regulation of RNF186, a ring finger E3 ligase that can modulate endoplasmic reticulum-stress pathway signaling (8) may be relevant to pathways underlying metastasis to the brain in human breast cancer.


2020 ◽  
Author(s):  
Shahan Mamoor

Breast cancer is one of the most common cancers in women and a leading cause of death for women (1). Metastasis, the spread of the cancer from the site of the primary tumor to a foreign site, is, in general, the reason why humans die from cancer (2). There are limited treatment options for women with metastatic breast cancer, which can spread from the breast to the brain (3). We compared the transcriptomes of 16 breast tumors to the transcriptomes of 16 brain metastases from the same patients using a published dataset (4). We discovered that 12 independent genes of the collagen family were among the genes whose expression was most different between primary breast tumors in humans and the brain metastases that they generate when considering the entire transcriptome. Each of these collagen genes were expressed at significantly lower levels in metastases to the brain than in tumors of the breast. The biology of collagen genes in the metastatic process in breast cancer should be evaluated as a novel therapeutic strategy in metastatic breast cancer.


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