Computational systems analysis of differential gene expression in brain metastatic breast cancer.

Differentially Expressed Genes ◽

Metastatic Breast ◽

Molecular Features ◽

Histone Lysine Methyltransferase ◽

Lysine Methyltransferase ◽

Differential Gene ◽

Computational Systems

We utilized readily available computational tools (1-5) and published microarray data (6-9) to understand in an unbiased fashion the most distinguishing molecular features of differentially expressed genes in brain metastatic tissues from humans with metastatic breast cancer, and their genomic sites. We present our findings here, which reveal enrichment for function at the Golgi apparatus, an overlap of molecular signatures with development of the lip and the craniofacial structure, and demonstrate that the genomic sites of the most differentially expressed genes in metastasis to the brain in human breast cancer are enriched for binding sites for Barx2 and IKZF1, may be occupied by Aebp2 and the histone lysine methyltransferase KMT2H, and marked at the chromatin at H3K79me2 and H3K4me3.

TSHZ3 is differentially expressed in lymph node metastasis in human breast cancer.

10.31219/osf.io/kxjqn ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Lymph Node Metastases ◽

Metastatic Breast ◽

Primary Tumors ◽

Node Metastases ◽

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that teashirt zinc finger homeobox 3, TSHZ3, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that TSHZ3 was also differentially expressed in brain metastatic tissues. TSHZ3 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of TSHZ3 in primary tumors of the breast was correlated with patient post-progression survival, in lymph node positive patients but not in lymph node negative patients. Modulation of TSHZ3 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.

TMEM98 is differentially expressed in lymph node metastasis in human breast cancer.

10.31219/osf.io/hpjc8 ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Lymph Node Metastases ◽

Metastatic Breast ◽

Primary Tumors ◽

Node Metastases ◽

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that transmembrane protein 98, TMEM98, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that TMEM98 was also differentially expressed in brain metastatic tissues. TMEM98 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of TMEM98 in primary tumors of the breast was correlated with patient overall survival, in lymph node positive patients but not in lymph node negative patients. Modulation of TMEM98 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.

CD69 is differentially expressed in the lymph nodes of patients with metastatic breast cancer.

10.31219/osf.io/utpcq ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Lymph Node Metastases ◽

Metastatic Breast ◽

Primary Tumors ◽

Node Metastases ◽

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that cluster of differentiation 69, CD69, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that CD69 was also differentially expressed in brain metastatic tissues. CD69 mRNA was present at increased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of CD69 in primary tumors of the breast was correlated with patient overall survival, more significantly in lymph node negative patients than in lymph node positive patients. Modulation of CD69 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.

MMP13 is differentially expressed and down-regulated in brain metastatic breast cancer.

10.31219/osf.io/hx2ur ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Brain Metastases ◽

Metastatic Breast ◽

Clinical Problem ◽

Gene Encoding ◽

Matrix Metalloproteinase 13 ◽

The Matrix ◽

Brain metastases are a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to discover genes associated with brain metastasis in patients with brain metastatic breast cancer. We found that the gene encoding the matrix metalloproteinase 13, MMP13, was among the genes most differentially expressed in the brain metastases of patients with brain metastatic breast cancer. MMP13 may be of relevance to the biology underlying metastasis to the brain in humans with metastatic breast cancer. MMP13 now joins MMP14, MMP11 and MMP2 among matrix metalloproteinases we have found to be differentially expressed and down-regulated in the brain metastases of humans with metastatic breast cancer (6-8).

GRIK3 is differentially expressed in the lymph nodes of patients with metastatic breast cancer.

10.31219/osf.io/zec8n ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Lymph Node Metastases ◽

Metastatic Breast ◽

Primary Tumors ◽

Node Metastases ◽

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that the glutamate receptor, ionotropic kainate subunit 3, GRIK3, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that GRIK3 was also differentially expressed in brain metastatic tissues. GRIK3 mRNA was present at increased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of GRIK3 in primary tumors of the breast was correlated with patient recurrence-free survival, in lymph node negative patients but not in lymph node positive patients. Modulation of GRIK3 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.

SFRP2 is differentially expressed in lymph node metastasis in human breast cancer.

10.31219/osf.io/y8nzv ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Lymph Node Metastases ◽

Metastatic Breast ◽

Primary Tumors ◽

Node Metastases ◽

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that secreted frizzled related protein 2, SFRP2, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that SFRP2 was also differentially expressed in brain metastatic tissues. SFRP2 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of SFRP2 in primary tumors of the breast was correlated with patient overall survival, in lymph node positive patients but not in lymph node negative patients. Modulation of SFRP2 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.

TSPY is differentially expressed in lymph node metastases in human breast cancer.

10.31219/osf.io/rwunm ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Lymph Node Metastases ◽

Metastatic Breast ◽

Primary Tumors ◽

Node Metastases ◽

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that the testis-specific protein on Y chromosome, TSPY, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that TSPY was also differentially expressed in brain metastatic tissues. TSPY mRNA was present at increased quantities in lymph node metastases as compared to primary tumors of the breast. Modulation of TSPY expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.

IL-6 is differentially expressed in the tumors of breast cancer patients treated with trastuzumab.

10.31219/osf.io/pcmnt ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Messenger Rna ◽

Growth Factor Receptor ◽

Metastatic Breast ◽

The United States ◽

Breast Cancer Patients ◽

Primary Tumors

Trastuzumab (Herceptin) is a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1) utilized for the treatment of adjuvant and metastatic breast cancer (2) in the United States and worldwide. We mined published microarray and gene expression data (3, 4) to discover in an unbiased manner the most striking transcriptional features of trastuzumab treatment. We identified the cytokine interleukin-6 (IL-6) (5) as among the genes most differentially expressed in the primary tumors of patients with breast cancer treated with trastuzumab. The primary tumors of breast cancer patients treated with trastuzumab expressed higher levels of IL-6 messenger RNA than did patients not treated with trastuzumab, and a single administration of trastuzumab was sufficient to result in differential expression of IL-6 in primary tumors of the breast, suggesting that increased primary tumor expression of IL-6 in the primary tumors of patients with breast cancer, a cytokine whose serum levels are correlated with worse patient survival outcomes in metastatic breast cancer (6), is a direct transcriptional result of treatment with trastuzumab.

TSPAN9 is differentially expressed in lymph node metastasis in human breast cancer.

10.31219/osf.io/8f5zj ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Lymph Node Metastases ◽

Metastatic Breast ◽

Primary Tumors ◽

Node Metastases ◽

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the breast and the brain reside the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in humans with metastatic breast cancer. We found that tetraspanin 9, TSPAN9, was among the genes whose expression was most different in the lymph node metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Analysis of a separate microarray dataset revealed that TSPAN9 was also differentially expressed in brain metastatic tissues. TSPAN9 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of TSPAN9 in primary tumors of the breast was correlated with patient distant metastasis-free survival, in lymph node positive patients but not in lymph node negative patients. Modulation of TSPAN9 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes and the brain in humans with metastatic breast cancer.

XCR1 is differentially expressed in brain metastatic human breast cancer.

10.31219/osf.io/gyqtf ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Tumor Cells ◽

Metastatic Breast ◽

Metastatic Tumor ◽

Clinical Problem ◽

Primary Tumors ◽

Free Survival ◽

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that the receptor for chemokines XCL1 and XCL2, the X-C motif chemokine receptor 1, encoded by XCR1, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast (4). XCR1 was also differentially expressed in the tumor cells of patients with triple negative breast cancer (5). XCR1 mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of XCR1 in primary tumors was significantly correlated with patient recurrence-free survival. Modulation of XCR1 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.