Differential and decreased expression of Fibulin 1, Fibulin 2, and Fibulin 5 in metastases to disparate organ sites in breast cancer.

Breast cancer is a leading killer of women in the United States (1) and the main reason women diagnosed with breast cancer die is metastasis, or spread of the cancer from the breast to a distant organ site (2, 3). We mined public datasets (4, 5) to perform systems-level analyses of the most significant differences in gene expression (6) between breast cancers in humans and the metastases they generate. We found that fibulin-1, fibulin-2 and fibulin-5 were among the genes whose expression was most different between primary tumors of the breast and metastases to both the brain and the soft tissues. Moreover, we found uniform and significantly decreased expression of each differentially expressed fibulin gene in both tissue types. Fibulins-1, -2 and -5 should be targeted to assess whether over-expression of these genes can halt, delay or reverse metastasis in women with breast cancer.

Aquaporin 4 over-expression in metastases to the brain in breast cancer.

10.31219/osf.io/yra9e ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Brain Metastases ◽

Water Channel ◽

Breast Tumors ◽

Aquaporin 4 ◽

Primary Breast Tumor ◽

Over Expression ◽

Patients With Cancer ◽

Public Datasets ◽

Brain metastases affect 10-15% of women with breast cancer (1). Metastasis is the most significant contributor to death in patients with cancer (2). We assessed what genes make brain metastases most different from the breast tumors from which they arose using public datasets (3, 4). The aquaporin 4 (AQP4) water channel (5) was one of the most differentially expressed genes in brain metastases when comparing the transcriptomes of matched tumor and metastasis samples from the brain and breast from 16 patients (2). Analysis of a separate dataset showed demonstrated the same result (4). In both cases, aquaporin 4 was expressed at significantly higher levels in metastases to the brain than in the primary breast tumor. This is the first report of aquaporin 4 differential over-expression in the brain metastases of patients with breast cancer.

Rab11 family-interacting protein 4, RAB11FIP4, is a differentially expressed gene in brain metastatic human breast cancer.

10.31219/osf.io/m32yb ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Differentially Expressed Gene ◽

Metastatic Breast ◽

Metastatic Tumor ◽

Clinical Problem ◽

Interacting Protein ◽

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 Rab11 family-interacting protein 4, encoded by RAB11FIP4, 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. RAB11FIP4 mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of RAB11FIP4 in primary tumors was significantly correlated with patient recurrence-free survival and distant metastasis-free survival. Modulation of RAB11FIP4 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.

COL16A1 is differentially expressed in lymph node metastasis in human breast cancer.

10.31219/osf.io/vczaw ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Lymph Node Metastases ◽

Metastatic Breast ◽

Lymphoid Organ ◽

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 collagen type XVI alpha 1 chain, COL16A1, 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. COL16A1 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of COL16A1 in primary tumors of the breast was correlated with patient overall survival, in lymph node negative patients but not in lymph node positive patients. Modulation of COL16A1 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.

COL6A1 is differentially expressed in lymph node metastasis in human breast cancer.

10.31219/osf.io/krvcj ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Lymph Node Metastases ◽

Metastatic Breast ◽

Lymphoid Organ ◽

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 collagen type VI alpha 1 chain, COL6A1, 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. COL6A1 mRNA was present at decreased quantities in lymph node metastases as compared to primary tumors of the breast. Importantly, expression of COL6A1 in primary tumors of the breast was correlated with patient post-progression survival, in lymph node negative patients but not in lymph node positive patients. Modulation of COL6A1 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.

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 ◽

Differentially Expressed ◽

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.

AKT1 is differentially expressed in primary tumors and brain metastases in humans with breast cancer.

10.31219/osf.io/m2ubf ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Brain Metastases ◽

Metastatic Breast ◽

Metastatic Tumor ◽

Clinical Problem ◽

Central Nervous System Metastasis ◽

Human Breast ◽

Primary Tumors ◽

Breast Tissues ◽

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 ◽

Differentially Expressed ◽

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.

TOM1L2 is a differentially expressed gene in human metastatic breast cancer, in the brain and in the lymph nodes.

10.31219/osf.io/y4am3 ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Lymph Nodes ◽

Differentially Expressed Gene ◽

Metastatic Breast ◽

Metastatic Tumor ◽

Clinical Problem ◽

Primary Tumors ◽

Node Metastases ◽

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 target of myb1-like 2, encoded by TOM1L2, was among the genes whose expression was most different in the brain and lymph node metastases of patients with metastatic breast cancer. TOM1L2 mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of TOM1L2 in primary tumors was significantly correlated with patient overall survival in patients with breast cancer. Modulation of TOM1L2 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain while evading immune clearance in the lymph nodes 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 ◽

Differentially Expressed ◽

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.

DIAPH2 is a differentially expressed gene in human metastatic breast cancer, in the brain and in the lymph nodes.

10.31219/osf.io/8hraz ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Lymph Node Metastases ◽

Differentially Expressed Gene ◽

Metastatic Breast ◽

Primary Tumors ◽

Node Metastases ◽

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 diaphanous homolog 2, encoded by DIAPH2, was among the genes whose expression was most different in the brain and lymph node metastases of patients with metastatic breast cancer. DIAPH2 mRNA was present at decreased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of DIAPH2 in primary tumors was significantly correlated with patient recurrence-free survival in patients with breast cancer. Modulation of DIAPH2 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain while evading immune clearance in the lymph nodes in humans with metastatic breast cancer. These data are one piece of evidence suggesting a common ancestor or tumor clone for brain and lymph node metastases that originate from the primary tumor, alluding to patterns in developmental origin and migratory pathways through the lymph node in human brain metastatic breast cancer.