The effect of miRNAs and MALAT1 related with the prognosis of Her-2 positive breast cancer patients with lymph node metastasis

2020 ◽  
Author(s):  
Zhao Hongcan ◽  
Yang Hongjian ◽  
Zhang Xiping

Abstract Background: To analyze and screen the miRNAs associated with lymph node metastasis of breast cancer (BC), and to explore the roles of these miRNAs in the proliferation, invasion and prognosis of BC. Methods: MicroRNAs associated with lymph node metastasis in Her-2 positive BC was screened by TCGA database. The qRT-PCR was used to verify theses 5 miRNAs in 30 cases of Her-2 positive BC with lymph node metastasis of different degree. The tumor tissue samples were divided into non-lymph node metastasis group, ≤ 3 lymph node metastasis group and > 3 lymph node metastasis group. In addition, 10 cases of paracancerous tissues were considered as paracancerous control group. Pearson correlation analysis was used to analysis the relationship of 5 miRNAs and MALAT1 with Her-2 positive BC patients' clinicopathological characteristics and prognosis. CCK8 and Transwell experiments were used to detect the effects of miR-143 and miR-455 on the proliferation and invasion of Her-2 positive BC cells (MDA-MB-453). Results: Five kinds of miRNA (miR-143, miR-196a, miR-455, miR-9 and miR-92a) related with Her-2 positive BC with lymph node metastasis were screened by TCGA database. The detecting results of qRT-PCR showed that the levels of miR-143, miR-196a, miR-9 and MALAT1 increased with the increased number of lymph nodes. The expression level of miR-143 in the group of ≤ 3 lymph nodes metastasis and > 3 lymph nodes metastasis was significantly higher than that in the group of non-lymph nodes metastasis (P<0.001), and that in the group of > 3 lymph nodes metastasis was significantly higher than that in the group of ≤ 3 lymph nodes metastasis (P<0.001). The expression level of miR-196a in the group of ≤ 3 lymph nodes metastasis and > 3 lymph nodes metastasis was significantly higher than that in the group of non-lymph nodes metastasis (P<0.001), and that in the group of > 3 lymph nodes metastasis was significantly higher than that in the group of ≤ 3 lymph nodes metastasis (P<0.001). The expression level of miR-455 in the group of ≤ 3 lymph nodes metastasis and > 3 lymph nodes metastasis was significantly lower than that in the group of non-lymph nodes metastasis (P<0.001), and that in the group of > 3 lymph nodes metastasis was significantly lower than that in the group of ≤ 3 lymph nodes metastasis (P<0.001). The expression level of MALAT1 in the group of ≤ 3 lymph nodes metastasis and > 3 lymph nodes metastasis was significantly higher than that in the group of non-lymph nodes metastasis (P<0.001), and that in the group of > 3 lymph nodes metastasis was significantly higher than that in the group of ≤ 3 lymph nodes metastasis (P<0.01). Pearson correlation analysis showed that the expression levels of miR-455-5p, miR-196a-5p and MALAT1 were negatively correlated, positively correlated and positively correlated with the pathological stages of Her-2 positive BC, respectively. The results of survival analysis showed that RFS of patients with high expression of miR-196a, miR-92a and MALAT1 was significantly lower than that of patients with low expression (P<0.05), and OS and RFS of patients with high expression of miR-9 were significantly lower than those of patients with low expression, while OS and RFS of patients with high expression of miR-455 were significantly higher than those of patients with low expression (P<0.05). Cytological experiments showed that up regulation of miR-455 significantly inhibited the proliferation and invasion of BC cells, while down regulation of miR-143 significantly inhibited the proliferation and invasion of BC cells and the expression of MALAT1 (P<0.05). Conclusion: High expression of miR-143, miR-9, miR-196a, MALAT1 and low expression of miR-455 are related to the degree of lymph node metastasis of Her-2-positive BC patients, indicating poor prognosis. Down-regulation of miR-455 and up-regulation of miR-143 and MALAT1 can promote the cell proliferation and invasion of Her-2-positive BC.

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 26-26
Author(s):  
Jun Liu ◽  
Xiaolong Fu ◽  
Hongxuan Li ◽  
Yan Cheng ◽  
Zhigang Li

Abstract Background Endoscopic submucosal dissection (ESD) can be used as a less invasive treatment option for early esophageal cancer. But how to prevent lymph node metastasis is essential in these patients. This study aimed to analyze prevalence of lymph nodes metastasis for T1b thoracic esophageal squamous cell carcinoma(TESCC) patients treated in Shanghai Chest Hospital(SCH) and to propose a clinical target volume (CTV) for additional radiotherapy Clinical Target Volume design following endoscopic submucosal dissection(ESD) in these patients. Methods From 2012 to 2017, consecutive patients with T1b TESCC patients who underwent complete resection in SCH were identified. The prevalence of lymph-node metastasis were assessed and evaluated whether these metastasis areas would be encompassed by our proposed CTV. We proposed lymph-node stations (JEOG) 101, 104, 105, 106, 107 for upper TESCC, lymph-node stations 106, 107, 108, 1, 2, 3, 7, 8, 9, 10 for middle TESCC, and lymph-node stations110, 112, 1, 2, 3, 7, 8, 9, 10 for lower TESCC. Results There were 240 patients (80.4% male) who met the inclusion criteria, with a mean age of 62 ± 7 years. Of the total, 27.1%(65/240) patients presented with lymph nodes metastasis. Single lymph-node and single station lymph-node metastasis among positive nodes patients were 63.1%(41/65) and 70.8%(46/65), respectively.Tumor length exceeding 20mm and poor tumor differentiation but not age, gender, tumor position and tumor thrombus were independently associated with the risk of nodal disease. Among positive nodes patients, 89.2% (58/65) lymph-node metastasis for T1b TESCC patients could be covered by proposed CTV. Conclusion Prevalence of lymph node metastasis is high in patients with T1b TESCC. It seemed additional radiotherapy after ESD for those patients with high risk factors is needed to prevent lymph node metastasis. Majority positive nodes area could be covered by our proposed CTV. However, the value of radiotherapy and the proposed CTV should be investigated in further prospective studies. Disclosure All authors have declared no conflicts of interest.


2019 ◽  
Vol 22 (3) ◽  
pp. 201-206
Author(s):  
Jiangshan Lian ◽  
Xiaolin Zhang ◽  
Yingfeng Lu ◽  
Shaorui Hao ◽  
Zhe Zhang ◽  
...  

Objective: To investigate the expression of long-chain non-coding RNA MINCR (LncRNAMINCR) and Cyclin-Dependent Kinase 2 (CDK2) mRNA in primary hepatocellular carcinoma, and to analyze the relationship between its expression and clinical pathological parameters and prognosis of hepatocellular carcinoma. Methods: Seventy-five surgically resected primary hepatocellular carcinoma tissues and paracancerous tissues were selected. Real-time PCR was used to detect the expression of LncRNA-MINCR and CDK2 mRNA in hepatocellular carcinoma tissues and adjacent tissues. The relationship of clinicopathological parameters and prognosis between hepatocellular carcinoma and LncRNA-MINCR and CDK2 mRNA were analyzed. Pearson correlation coefficient describes the correlation between LncRNA-MINCR and CDK2 mRNA. Results: The expression of LncRNA-MINCR and CDK2 mRNA in primary hepatocellular carcinoma tissues was higher than that in the adjacent tissues [(5.51±0.62) vs (1.62±0.51), (4.52±0.73) vs (1.85±0.95), P<0.05]. The expression of LncRNA-MINCR in the primary hepatocellular carcinoma group was positively correlated with CDK2 mRNA (r=0.352, P<0.05), and the expression of LncRNA-MINCR in the paracancerous tissue group was not correlated with CDK2 mRNA (r=0.024, P>0.05). LncRNA-MINCR expression was associated with TNM staging, lymph node metastasis, and cirrhosis (P<0.05). CDK2 mRNA expression was associated with tumor diameter, TNM stage, lymph node metastasis, and serum alpha-fetoprotein levels (P<0.05). The 3-year survival rate of patients with high expression of LncRNAMINCR was lower than that of LncRNA-MINCR low expression group [53.49% vs 77.38%, 2=13.024, P<0.05). The 3-year survival rate of patients with high CDK2 mRNA expression was lower than that of CDK2 mRNA low expression group [51.29] % vs 80.38%, 2 = 10.15, P < 0.05]. Conclusion: The expression of LncRNA-MINCR and CDK2 mRNA in primary hepatocellular carcinoma tissues increased significantly. The two play a synergistic role in the invasion, invasion and metastasis of hepatocarcinoma cells. High expression of LncRNA-MINCR and CDK2 mRNA indicates poor prognosis in patients with hepatocellular carcinoma.


2021 ◽  
Author(s):  
Jian Shen ◽  
Yi Li ◽  
Qiong Wu ◽  
Yilun Liu ◽  
Anqi Jin ◽  
...  

Abstract Background Molecular marker is on the hot spot for thyroid tumor research in the recent years. The purpose of this study is try to clarify the value of HMGA2 for differential diagnosis between benign and malignant thyroid nodules in order to further assessing the risk of simultaneous cervical lymph nodes metastasis. Methods With a total of 125 thyroid samples, including 85 papillary thyroid carcinomas, 20 follicular thyroid adenomas and 20 normal thyroid tissue were retrospectively analyzed, and we compare expression level of HMGA2 protein among these three groups in this study. PTC group was then subdivided according to the number of metastasis lymph nodes in order to explore the possibility of using HMGA2 protein to predict invasion of lymph nodes in PTC. We also compare the efficiency of BRAFV600E mutation and HMGA2 expression level in the prediagnosis of cervical lymph node metastasis during the experiment. Results Expression rate of HMGA2 protein in PTC was measured at 100%, which has significant statistical differences with HMGA2 in FTA and NT (P < 0.05). Moreover, there was no significant correlation between expression level of HMGA2 and the size of PTC; whether it accompanied by Hashimoto's thyroiditis; high expression level of HMGA2 could be more sensitive in the prediagnosis of cervical lymph node metastasis than BRAFV600E mutation. Conclusion ①HMGA2 protein can be used as a molecular marker for differential diagnosis of benign and malignant thyroid nodules. ②The expression level of HMGA2 protein is correlated with cervical lymph node metastasis in papillary thyroid carcinoma, performing an auxiliary value for clinical decision.


Author(s):  
Ana Cernea ◽  
Juan Luis Fernández-Martínez ◽  
Enrique J. deAndrés-Galiana ◽  
Enrique J. deAndrés-Galiana ◽  
José A. Galván ◽  
...  

Background: Triple Negative Breast Cancer (TNBC) is a type of breast cancer with very bad prognosis. Predicting the histological grade (HG) and the lymph nodes metastasis is crucial for developing more suitable treatment strategies. Methods: We present the main clinical and pathological variables to predict the histological grade and lymph nodes metastasis via novel machine learning techniques. These variables are currently being used for prognosis and treatment in medical practice. This analysis was performed using a database of 102 Caucasian women diagnosed with TNBC. The results were cross-validated using random simulations of this dataset. Results: HG was predicted with an accuracy of 93.8% using a list of 6 prognostic variables with significant implications: Ki67 expression, use of Oral contraceptives, Col11A1 expression, Col11A1 score, E-cad truncated and Tumor size. The lymph nodes metastasis was predicted with an accuracy of almost 85% using only 6 prognostic variables: Vascular invasion, Tumor size, Perineural invasion, Age at diagnosis, Ki67 expression, and Col11A1 score. This analysis also served to establish the median signatures of the groups with and without lymph node metastasis, and proved the existence of a kind of small-size tumors (around 2.15 cm) with lymph node metastasis but not showing vascular and perineural invasions and higher protein Col11A1 score. Besides, these signatures proved to be very stable. Conclusions: The additional information conveyed by the prognostic variables found in these two classification problems provides new insight about the genesis and progression of this disease and can be used in medical practice to improve decisions in patient diagnosis and further treatment.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Peng Qie ◽  
Qifan Yin ◽  
Xuejiao Xun ◽  
Yongbin Song ◽  
Shaohui Zhou ◽  
...  

Abstract Background Esophageal squamous cell carcinoma(ESCC) is one of the most common tumors worldwide. Esophagectomy with three-field lymph node dissection(3FLND) is the radical surgical procedure for esophageal cancer. However, 3FLND is not widely used due to it’s higher mortality rate and higher incidence of postoperative complications. There is an urgent need to identify novel biomarkers that can guide the most proper lymph-node dissection in esophageal cancer patients. Method Ninety-two patients with thoracic ESCC undergoing 3FLND were enrolled into our study from the Department of Thoracic Surgery of the Fourth Hospital affiliated to the Hebei Medical University and Hebei General Hospital between Jun 2011 and Dec 2015. Retrospectively collected data from these 92 patients was used to explore the relationship between the lymph-node metastasis、recurrence and the SPRY4-IT1 expression level and to determine whether 3FLND should be performed in patients with thoracic ESCC. Results The findings revealed that the SPRY4-IT1 expression was significantly higher in esophageal cancer tissues than in adjacent noncancerous tissues. (P < 0.01). Furthermore, the high expression of SPRY4-IT1 was significantly correlated with tumor differentiation (P = 0.029), T classification (P = 0.013), lymph node metastasis(P = 0.022) and pathological stage (P = 0.001). The increased expression of SPRY4-IT1 was associated with a higher risk of cervical and superior mediastinal lymph-node metastasis(P = 0.039).However, no significant association was observed between the risk of cervical and superior mediastinal lymph-node recurrence and the SPRY4-IT1 expression level in the thoracic ESCC patients performed 3FLND(P = 0.509). Conclusions Our data support the assumption that the high expression of SPRY4-IT1 is associated with a high risk of lymph node metastasis and it has potential application as a indicator for guiding on three-field lymph node dissection in patients with thoracic ESCC. Randomized controlled trials with a large cohort of patients will be needed to confirm this conclusion in the future.


2020 ◽  
Author(s):  
Kai Zhang ◽  
Changcheng Tao ◽  
Jianxiong Wu ◽  
Weiqi Rong

Abstract Background: Lymph node (LN) metastasis is associated with poor survival outcomes in patients with hepatocellular carcinoma (HCC) patients and because of the reported low probability of lymph node metastasis, research into the Anchorprognoses of such patients is difficult to conduct. In this study, we aimed to develop a nomogram model to predict the prognosis of HCC patients with lymph node metastasis. Methods: HCC patients diagnosed with LN metastasis from 2010 to 2015 were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate Cox regression and lasso regression were used to screen prognostic factors. Cox multiple-factor analysis was used to investigate the independent risk factors for survival. We developed a prognostic nomograms using these independent risk factors. The predictive performance of our nomogram model was evaluated according to the concordance index (C-index) and calibration curve. The net clinical benefit was assessed via decision curve analysis (DCA). Patients were divided into different risk groups according to the model. A survival curve was drawn using the Kaplan-Meier method and the difference was compared by the log-rank test. Results: There were 944 patients in the training cohort and 402 patients in the validation cohort. Grade, T stage, surgery to the liver, chemotherapy, radiation recode, AFP, fibrosis score, tumor size group, M stage were selected as independent prognostic factors, and we developed nomograms using these variables. The calibration curves for probability of survival showed good agreement between the prediction by our model and actual observation in both the training and validation groups. DCA indicated that the nomogram had positive net benefits. Conclusions: The nomogram can accurately predict the prognosis of HCC patients with lymph nodes metastasis and provide a reasonable basis for treatment. Keywords: Hepatocellular carcinoma, prognosis, lymph nodes metastasis, prediction model, nomogram


2020 ◽  
Author(s):  
Peng Qie ◽  
Qifan Yin ◽  
Xuejiao Xun ◽  
Yongbin Song ◽  
Shaohui Zhou ◽  
...  

Abstract Backgroup:Esophageal squamous cell carcinoma(ESCC) is one of the most common tumors worldwide. Esophagectomy with three-field lymph node dissection(3FLND) is the radical surgical procedure for esophageal cancer. However, 3FLND is not widely used due to it’s higher mortality rate and higher incidence of postoperative complications. There is an urgent need to identify novel biomarkers that can guide the most proper lymph-node dissection in esophageal cancer patients.Method:Ninety-two patients with thoracic ESCC undergoing 3FLND were enrolled into our study from the Department of Thoracic Surgery of the Fourth Hospital affiliated to the Hebei Medical University and Hebei General Hospital between Jun 2011 and Dec 2015. Retrospectively collected data from these 92 patients was used to explore the relationship between the lymph-node metastasis、recurrence and the SPRY4-IT1 expression level and to determine whether 3FLND should be performed in patients with thoracic ESCC. Results: The findings revealed that the SPRY4-IT1 expression was significantly higher in esophageal cancer tissues than in adjacent noncancerous tissues. (P<0.01). Furthermore, the high expression of SPRY4-IT1 was significantly correlated with tumor differentiation (P=0.029), T classification (P=0.013), lymph node metastasis(P=0.022) and pathological stage (P=0.001). The increased expression of SPRY4-IT1 was associated with a higher risk of cervical and superior mediastinal lymph-node metastasis(P = 0.039).However, no significant association was observed between the risk of cervical and superior mediastinal lymph-node recurrence and the SPRY4-IT1 expression level in the thoracic ESCC patients performed 3FLND(P=0.509). Conclusions: Our data support the assumption that the high expression of SPRY4-IT1 is associated with a high risk of lymph node metastasis and it has potential application as a indicator for guiding on three-field lymph node dissection in patients with thoracic ESCC. Randomized controlled trials with a large cohort of patients will be needed to confirm this conclusion in the future.


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.


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