Lower expression of miR-218 in human breast cancer is associated with lymph node metastases, higher grades, and poorer prognosis

Breast cancer is considered as the most prevalent malignancy in women worldwide. Despite emergence of several prognosticators for better management of patients, there are still limitations for their clinical application due to the complexity of breast tumors, and therefore, new biomarkers for better prognosis of clinical outcomes would be of the great essence. MicroRNAs are highly conserved small non-coding regulatory RNAs involved in post-transcriptional regulating of gene expression during different cellular mechanisms. Accumulating studies suggest that miR-218 plays a multifunctional role in various cancer types and different stages. Here, to address prognostic significance of miR-218 in breast cancer, we investigate the expression profile of miR-218 and B-cell-specific Moloney murine leukemia virus integration site 1 ( BMI1) gene, as one of the putative targets of miR-218, in 33 paired breast tumors and their adjacent normal tissues with respect to the clinicopathological features of patients using quantitative real-time polymerase chain reaction. The correlation of both miR-218 and BMI1 gene expression with overall survival of breast cancer patients was also examined recruiting OncoLNC data portal. Finally, to better understand biological function of miR-218 in breast cancer, we performed in silico Gene Ontology and signaling pathway enrichment analysis on miR-218 targetome. According to our data, significant elevation of the expression of miR-218 and downregulation of BMI1 were observed in clinical breast cancer specimens compared with normal tissues ( p < 0.0001). The lower expression of miR-218 was associated with lymph node metastases, higher grades, and poorer prognosis (logrank p = 0.00988), whereas no significant difference in overall survival was observed between patients with higher and lower expression of BMI1 (logrank p = 0.254). These findings suggest that miR-218 expression profiling might be clinically applicable as a prognostic biomarker in breast cancer. In addition, our in silico enrichment analyses revealed that the association of miR-218 expression with breast cancer prognosis might be through its involvement in endocytosis and gap junction biological pathways.

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Tumor Microenvironment of Metastasis (TMEM) Doorways Are Restricted to the Blood Vessel Endothelium in Both Primary Breast Cancers and Their Lymph Node Metastases

Cancers ◽

10.3390/cancers11101507 ◽

2019 ◽

Vol 11 (10) ◽

pp. 1507 ◽

Cited By ~ 4

Author(s):

Ginter ◽

Karagiannis ◽

Entenberg ◽

Lin ◽

Condeelis ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Tumor Microenvironment ◽

Lymph Nodes ◽

Lymph Node Metastases ◽

Lymphatic Vessels ◽

Breast Tumors ◽

Primary Tumors ◽

Hematogenous Dissemination ◽

Node Metastases

Cancer cells metastasize from primary tumors to regional lymph nodes and distant sites via the lymphatic and blood vascular systems, respectively. Our prior work has demonstrated that in primary breast tumors, cancer cells utilize a three-cell complex (known as tumor microenvironment of metastasis, or TMEM) composed of a perivascular macrophage, a tumor cell expressing high levels of the actin-regulatory protein mammalian enabled (Mena), and an endothelial cell as functional “doorways” for hematogenous dissemination. Here, we studied a well-annotated case–control cohort of human invasive ductal carcinoma of the breast and metastatic lymph nodes from a separate breast cancer cohort. We demonstrate that in primary breast tumors, blood vessels are always present within tumor cell nests (TCNs) and tumor-associated stroma (TAS), while lymphatic vessels are only occasionally present in TCN and TAS. Furthermore, TMEM doorways not only exist in primary tumors as previously reported but also in lymph node metastases. In addition, we show that TMEM intravasation doorways are restricted to the blood vascular endothelium in both primary tumors and lymph node metastases, suggesting that breast cancer dissemination to distant sites from both primary tumors and metastatic foci in lymph nodes occurs hematogenously at TMEM doorways. TMEMs are very rarely detected at lymphatic vessels and do not confer clinical prognostic significance, indicating they are not participants in TMEM-associated hematogenous dissemination. These findings are consistent with recent observations that hematogenous dissemination from lymph nodes occurs via blood vessels.

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The expression of Dicer and Drosha in matched normal tissues, tumours and lymph node metastases in triple negative breast cancer

BMC Cancer ◽

10.1186/1471-2407-14-253 ◽

2014 ◽

Vol 14 (1) ◽

Cited By ~ 22

Author(s):

Kelly A Avery-Kiejda ◽

Stephen G Braye ◽

John F Forbes ◽

Rodney J Scott

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Triple Negative Breast Cancer ◽

Lymph Node Metastases ◽

Triple Negative ◽

Normal Tissues ◽

Node Metastases

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Lipoma HMGIC fusion partner expression differs in primary tumors and lymph node metastases in malignancy.

10.21203/rs.3.rs-591947/v2 ◽

2021 ◽

Author(s):

Vijay S

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Lymph Node Metastases ◽

Cancer Metastasis ◽

Breast Tumors ◽

Breast Cancer Metastasis ◽

Axillary Lymph ◽

Node Metastasis ◽

Node Metastases

Abstract Breast cancer is the most common cancer found in women. 1. Metastasis is the leading cause of mortality among cancer patients. 2. As the number of axillary lymph nodes with metastases grows the prognosis for patients with breast cancer worsens3. We used a published microarray dataset4 to find genes linked to lymph node metastasis, which is an early stage of breast cancer metastasis. When comparing original breast tumors to lymph node metastases from patients diagnosed with breast cancer, we discovered substantial differences in LHFP gene expression. When comparing primary breast tumors to neighboring normal breast tissue, LHFP was shown to be one of the most differentially expressed genes in a separate microarray dataset5. In individuals with breast cancer, LHFP expression was shown to be substantially linked with median overall survival. LHFP may be involved in the mechanisms that lead to the transformation or progression of the original tumor in human breast cancer, as well as lymph node metastasis. Breast cancer, breast cancer metastasis, lymph node metastasis, LHFP, breast cancer systems biology, and breast cancer targeted treatments.

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