Methylation profiles of genes in breast cancer luminal HER2-negative primary tumor during regional lymphnode metastasis

2021 ◽  
Vol 67 (1) ◽  
pp. 88-94
Author(s):  
A.M. Krasnyi ◽  
S.V. Kurevlev ◽  
A.A. Sadekova ◽  
T.G. Sefikhanov ◽  
V.V. Kometova ◽  
...  

Aberrant methylation is strongly associated with development of cancer, but limited data exist on correlation between methylation and regional lymph node metastasis (RLNM). The aim of this research was to study using of methylation levels of WIF1, RASSF1A, CDO1 and MEST aberrant methylated genes in a primary breast cancer for prediction of regional lymph node metastases. We used MS-HRM (Methylation Sensitive High Resolution Melting) to assess methylation levels. The results were confirmed by pyrosequencing. The study included 66 women with LumA and 46 women with HER2- (LumB-), 22 and 26 of them had metastasis in at least one lymph node respectively. It was found that methylation levels between LumA and LumB subtypes differed significantly in genes: WIF1 (p<0.001), CDO1 (p=0.002) and MEST (p=0.033). In the Lum A subtype statistically significant differences in level of methylation of WIF1 gene between patients with metastases in RLNM and patients without metastases were found (p=0.03). Analysis of tumors longer than 2 cm in the LumA subtype, revealed an increase of statistical significance of WIF1 gene — p=0.009 (AUC (95%CI) = 0.76 (0.59−0.93)). In LumB- subtype RASSF1A, CDO1 and MEST had statistically significant differences in methylation level between groups (p=0.03, p=0.048 and p=0.045 respectively). ROC analysis showed that combining of three genes by logistic regression, AUC (95%CI) was 0.74 (0.6−0.88). Analysis of tumors longer than 2 cm, did not increase statistical significance for these genes (p=0.046; p=0.089 and p=0.076, respectively). Thus, the study of methylation in primary tumors may be useful for prediction of lymph node metastasis, as well as for better understanding of biological process inside breast cancer.

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7081 ◽  
Author(s):  
Li-hua Bian ◽  
Min Wang ◽  
Jing Gong ◽  
Hong-hong Liu ◽  
Nan Wang ◽  
...  

Background The objective of this study was to compare the diagnostic value of integrated PET/MRI with PET/CT for assessment of regional lymph node metastasis and deep myometrial invasion detection of endometrial cancer. Methods Eighty-one patients with biopsy-proven endometrial cancer underwent preoperative PET/CT (n = 37) and integrated PET/MRI (n = 44) for initial staging. The diagnostic performance of PET/CT and integrated PET/MRI for assessing the extent of the primary tumor and metastasis to the regional lymph nodes was evaluated by two experienced readers. Histopathological and follow-up imaging results were used as the gold standard. McNemar’s test was employed for statistical analysis. Results Integrated PET/MRI and PET/CT both detected 100% of the primary tumors. Integrated PET/MRI proved significantly more sensitivity and specificity than PET/CT in regional lymph node metastasis detection (P = 0.015 and P < 0.001, respectively). The overall accuracy of myometrial invasion detection for PET/CT and Integrated PET/MRI was 45.9% and 81.8%, respectively. Integrated PET/MRI proved significantly more accurate than PET/CT (P < 0.001). Conclusion Integrated PET/MRI, which complements the individual advantages of MRI and PET, is a valuable technique for the assessment of the lymph node metastasis and myometrial invasion in patients with endometrial 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 GRB2-binding adaptor protein, transmembrane, encoded by GAPT, 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. GAPT mRNA was present at increased quantities in lymph node metastatic tissues as compared to primary tumors of the breast. Expression of GAPT in primary tumors was significantly correlated with patient overall survival in lymph node positive patients but not in lymph node negative patients. Modulation of GAPT expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph node in humans with metastatic breast cancer.


BJR|Open ◽  
2019 ◽  
Vol 1 (1) ◽  
pp. 20180023
Author(s):  
Xu Dong ◽  
Yu Chunrong ◽  
Hou Hongjun ◽  
Zhang Xuexi

Objective: Lymph node metastasis is an important trait of breast cancer, and tumors with different lymph node statuses require various clinical treatments. This study was designed to evaluate the lymph node metastasis of breast cancer through pharmacokinetic and histogram analysis via dynamic contrast-enhanced (DCE) MRI. Methods and materials: A retrospective analysis was conducted to quantitatively evaluate the lymph node statuses of patients with breast cancer. A total of 75 patients, i.e. 34 patients with lymph node metastasis and 41 patients without lymph node metastasis, were involved in this research. Of the patients with lymph node metastases, 19 had sentinel lymph node metastasis, and 15 had axillary lymph node metastasis. MRI was conducted using a 3.0 T imaging device. Segmentation was carried out on the regions of interest (ROIs) in breast tumors under DCE-MRI, and pharmacokinetic and histogram parameters were calculated from the same ROIs. Mann–Whitney U test was performed, and receiver operating characteristic curves for the parameters of the two groups were constructed to determine their diagnostic values. Results: Pharmacokinetic parameters, including Ktrans, Kep, area under the curve of time–concentration, and time to peak, which were derived from the extended Tofts linear model for DCE-MRI, could highlight the tumor areas in the breast and reveal the increased perfusion. Conversely, the pharmacokinetic parameters showed no significant difference between the patients with and without lymph node metastases. By contrast, the parameters from the histogram analysis yielded promising results. The entropy of the ROIs exhibited the best diagnostic ability between patients with and without lymph node metastases (p < 0.01, area under the curve of receiver operating characteristic = 0.765, specificity = 0.706, sensitivity = 0.780). Conclusion: In comparison with the pharmacokinetic parameters, the histogram analysis of the MR images could reveal the differences between patients with and without lymph node metastases. The entropy from the histogram indicated that the diagnostic ability was highly sensitive and specific. Advances in knowledge: This research gave out a promising result on the differentiating lymph node metastases through histogram analysis on tumors in DCE-MR images. Histogram could reveal the tumors heterogenicity between patients with different lymph node status.


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 fucose mutarotase, encoded by FUOM, 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 FUOM was also differentially expressed in brain metastatic tissues (5). FUOM mRNA was present at increased quantities in lymph node metastatic tissues as compared to primary tumors of the breast. Expression of FUOM in primary tumors was correlated with patient overall survival in lymph node positive patients but not in lymph node negative patients. Modulation of FUOM expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph node 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 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 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Yu Min ◽  
Xiaoyuan Wei ◽  
Hang Chen ◽  
Ke Xiang ◽  
Guobing Yin ◽  
...  

Background. Pure mucinous breast cancer (PMBC) has a better prognosis than other types of invasive breast cancer. However, regional lymph node metastasis (LNM) might reverse this outcome. We aim to determine the independent predictive factors for regional LNM and further develop a nomogram model for clinical practice. Method. Data of PMBC patients from the Surveillance, Epidemiology, and End Results (SEER) program between Jan 2010 and Dec 2015 were retrospectively reviewed. Univariate and multivariate logistic regression analyses were used to determine the risk factors for LNM in T1-2 MBC. The nomogram was constructed and further evaluated by an internal validation cohort. The receiver operating characteristic (ROC) curves, decision curve analysis (DCA), and calibration curves were performed to evaluate the accuracy of this model. Result. Five variables, including age, race, tumor size, grade, and breast subtype, were identified to be significantly associated with regional LNM in female patients with T1-2 PMBC. A nomogram was successfully established with a favorable concordance index (C-index) of 0.780, supported by an internal validation cohort with a C-index of 0.767. Conclusion. A nomogram for predicting regional LNM in female patients with T1-2 PMBC was successfully established and validated via an internal cohort. This visualized model would assist surgeons to make appropriate clinical decisions in the management of primary PMBC, especially in terms of whether axillary lymph node dissection (ALND) is warranted.


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