Tyrosine kinase receptor AXL in human breast cancer is expressed differentially in metastasis of the lymph node

2021 ◽  
Author(s):  
Mairead Paul ◽  
Brandon Weston ◽  
Oliwier Morin

The most diagnosed malignancy in women is breast cancer1. Metastases in people diagnosed with cancer are the main cause of mortality. 2. Patients with breast cancer are predicted to do worse as the number of metastasized axillary lymph nodes increases3. In order to uncover the genes related with metastases in lymph nodes, the early events of the breast cancer metastasis, we mined the published and multiplexed mRNA quantitation datasets4, 5. When lymph node metastasis was compared to original breast tumors by patients diagnosed with breast cancer, we identified substantial differential expression of AXL encoding. The lower expression of AXL in primary tumors is associated with reduced disease-free survival in patients with breast cancer. AXL may be important in mechanisms that underlie lymph node metastasis.

2020 ◽  
Author(s):  
Shahan Mamoor

Breast cancer is the most frequently diagnosed cancer in women (1). Metastasis is the major cause of death in patients diagnosed with cancer (2). Prognosis for patients with breast cancer worsens as the number of axillary lymph nodes with metastasis increases (3). We mined published microarray and multiplexed mRNA quantitation datasets (4, 5) to discover genes associated with metastasis to the lymph nodes, an early event in breast cancer metastasis. We found significant differential expression of the gene encoding AXL when comparing lymph node metastases to primary breast tumors from women diagnosed with breast cancer. In primary tumors, lower expression of AXL correlated with decreased disease-free survival in breast cancer patients. AXL may be of relevance to processes underlying metastasis to the lymph nodes.


2021 ◽  
Vol 11 ◽  
Author(s):  
Yurong Zhou ◽  
Jinxuan Hou ◽  
Ning Meng ◽  
Staiculescu Daniel ◽  
Jiang Chen ◽  
...  

The axillary lymph nodes are the primary group responsible for lymphatic drainage in the breast and, consequently, are the most common location for breast cancer metastasis. However, lymphatic pathways running from the breast, via intercostal spaces, to parasternal lymph vessels have also been identified. According to the American Joint Committee on Cancer eighth edition manual, regional lymph node metastasis normally travels to the ipsilateral axillary, supraclavicular, subclavicular, and internal mammary lymph nodes. The presence of intercostal metastasis is out the range of these regional lymph nodes. It is very rare for intercostal lymph nodes to be the extra-axillary site of metastasis in breast cancer, and it has been little reported on in the literature. Despite its rarity, it has the capacity to adversely affect the prognosis of breast cancer and drastically influence treatment choice. Here, we analyze such a case, with a patient receiving a radical mastectomy and metastatic intercostal lymph node dissection due to the presence of intercostal lymph node metastasis indicated via MRI. Furthermore, the potential application of preoperative 3-dimensional (3D) visualization and surgical planning is also discussed.


Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 757
Author(s):  
Sanaz Samiei ◽  
Renée W. Y. Granzier ◽  
Abdalla Ibrahim ◽  
Sergey Primakov ◽  
Marc B. I. Lobbes ◽  
...  

Radiomics features may contribute to increased diagnostic performance of MRI in the prediction of axillary lymph node metastasis. The objective of the study was to predict preoperative axillary lymph node metastasis in breast cancer using clinical models and radiomics models based on T2-weighted (T2W) dedicated axillary MRI features with node-by-node analysis. From August 2012 until October 2014, all women who had undergone dedicated axillary 3.0T T2W MRI, followed by axillary surgery, were retrospectively identified, and available clinical data were collected. All axillary lymph nodes were manually delineated on the T2W MR images, and quantitative radiomics features were extracted from the delineated regions. Data were partitioned patient-wise to train 100 models using different splits for the training and validation cohorts to account for multiple lymph nodes per patient and class imbalance. Features were selected in the training cohorts using recursive feature elimination with repeated 5-fold cross-validation, followed by the development of random forest models. The performance of the models was assessed using the area under the curve (AUC). A total of 75 women (median age, 61 years; interquartile range, 51–68 years) with 511 axillary lymph nodes were included. On final pathology, 36 (7%) of the lymph nodes had metastasis. A total of 105 original radiomics features were extracted from the T2W MR images. Each cohort split resulted in a different number of lymph nodes in the training cohorts and a different set of selected features. Performance of the 100 clinical and radiomics models showed a wide range of AUC values between 0.41–0.74 and 0.48–0.89 in the training cohorts, respectively, and between 0.30–0.98 and 0.37–0.99 in the validation cohorts, respectively. With these results, it was not possible to obtain a final prediction model. Clinical characteristics and dedicated axillary MRI-based radiomics with node-by-node analysis did not contribute to the prediction of axillary lymph node metastasis in breast cancer based on data where variations in acquisition and reconstruction parameters were not addressed.


Author(s):  
Huswatun Hasanah ◽  
Rina Masadah ◽  
Berti J. Nelwan ◽  
Djumadi Achmad ◽  
Upik A. Miskad ◽  
...  

Background: Breast cancer is the second most common cancer in the world and is the most epidemic cancer in women, with approximately 1.67 million cases. Metastasis of tumor cells to other organs is a major cause of the increasing trend of mortality in breast cancer. This study aims to analyze the expression of c-Met associated with metastasis to axillary lymph nodes in invasive breast cancer.Method: The research was conducted at the Laboratory of Anatomical Pathology of Hasanuddin University Hospital. Stratified sampling was performed from January 2014 - January 2019. Immunohistochemical staining technique was applied upon 66 collected samples, followed by evaluating the c-Met expression score in invasive breast cancer group with positive and negative lymph node status.Result: c-Met overexpression was found among the invasive breast cancer incidence with lymph node metastasis. Among 50 cases with c-Met overexpression (c-Met positive), 40 cases (80%) of invasive breast cancer with lymph node metastasis were identified, while 10 cases (20%) were found in invasive breast cancer without metastasis to lymph nodes. On 16 cases with negative c-Met, 3 cases (18.8%) were found in invasive breast cancer with lymph node metastasis, and 13 cases (81.3%) in invasive breast cancer without metastasis to the lymph nodes. The statistical test results indicated a significant correlation between c-Met expression scores and metastasis to axillary lymph nodes in invasive breast cancer (p <0.001).Conclusion: As one of biomarkers, c-Met overexpression plays a vital role in the treatment of patients with invasive breast cancer to predict patient outcomes and to determine modalities. It is possible to apply c-Met overexpression to investigate aggressiveness of metastatic tumor cells in the future.


2021 ◽  
Author(s):  
Shahan Mamoor

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 lymph node metastasis in humans with metastatic breast cancer. We found that cartilage oligomeric matrix protein, encoded by COMP, 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 COMP was also differentially expressed in brain metastatic tissues5. COMP mRNA was present at increased quantities in lymph node metastatic tissues as compared to primary tumors of the breast. Expression of COMP in primary tumors was correlated with patient recurrence-free survival in lymph node negative patients but not in lymph node positive patients. Modulation of COMP expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes in humans with metastatic breast cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

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 lymph node metastasis in humans with metastatic breast cancer. We found that protein tyrosine phosphatase, receptor type C associated protein, encoded by PTPRCAP, 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 PTPRCAP was also differentially expressed in brain metastatic tissues5. PTPRCAP mRNA was present at increased quantities in lymph node metastatic tissues as compared to primary tumors of the breast. Expression of PTPRCAP in primary tumors was correlated with patient distant metastasis-free survival in lymph node negative patients but not in lymph node positive patients. Modulation of PTPRCAP expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes in humans with metastatic breast cancer.


2021 ◽  
Author(s):  
Shahan Mamoor

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 lymph node metastasis in humans with metastatic breast cancer. We found that cluster of differentiation 226, encoded by CD226, 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 CD226 was also differentially expressed in brain metastatic tissues (5). CD226 mRNA was present at increased quantities in lymph node metastatic tissues as compared to primary tumors of the breast. Expression of CD226 in primary tumors was correlated with patient overall survival in lymph node negative patients but not in lymph node positive patients. Modulation of CD226 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph nodes in humans with metastatic breast cancer.


2021 ◽  
Author(s):  
Kun Xu ◽  
Wenwen Zhang ◽  
Cong Wang ◽  
Longfei Hu ◽  
Runtian Wang ◽  
...  

Abstract The potentially different genetics and epigenetics in the primary tumors and metastases affect the efficacy of treatment in breast cancer patients. Nevertheless, the cellular and molecular mechanisms of breast cancer lymph node metastasis still remain elusive. Here, we employed single-cell RNA sequencing to acquire the transcriptomic profiles of individual cells from primary tumors, negative lymph nodes (NLs) and positive lymph nodes (PLs). We also performed a single-cell assay for transposase-accessible chromatin (ATAC) sequencing (scATAC-seq) of the positive and NL samples to get the chromatin accessibility profile. We identified a novel cell subpopulation with an abnormally high expression level of CXCL14 in the PL of breast cancer patients. Cell trajectory analysis also revealed that CXCL14 was increased expressed in the late pseudo-time. Moreover, based on a tissue microarray of 55 patients and the Oncomine database, we validated that CXCL14 expression was significantly higher in breast cancer patients with lymph node metastasis. Furthermore, scATAC-seq identified several transcription factors that may be potential regulation factors for the lymph node metastasis of breast cancer. Thus, our findings will improve our current understanding of the mechanism for lymph node metastasis, and they are potentially valuable in providing novel prognosis markers for the lymphatic metastasis of breast cancer.


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