The aim of this study was to identify some biomarkers for predicting lymph node metastasis and prognosis of human epidermal growth factor receptor 2(Her-2)-positive breast cancer(BC). We analyzed correlations between ...The aim of this study was to identify some biomarkers for predicting lymph node metastasis and prognosis of human epidermal growth factor receptor 2(Her-2)-positive breast cancer(BC). We analyzed correlations between micro RNAs(mi RNAs) and the prognosis of patients with BC based on data collected from The Cancer Genome Atlas(TCGA) database. The expression levels of mi R-455, mi R-143, and mi R-99 a were measured in clinical samples of Her-2-positive BC patients with different degrees of lymph node metastasis. We investigated the impacts of overexpressed mi R-455 on the proliferation and invasiveness of MDA-MB-453 cells and measured its effects on the expression of long non-coding RNA(lnc RNA) metastasis-associated lung adenocarcinoma transcript 1(MALAT1) by quantitative real-time polymerase chain reaction(q RT-PCR). The expression of mi R-455 was significantly and positively correlated to the prognosis and overall survival(OS) of the BC(P=0.028), according to TCGA information. The expression level of mi R-455 was positively correlated with OS and relapse-free survival(RFS) of patients with Her-2-positive BC, and was negatively correlated with the number of metastatic lymph nodes(P<0.05). Transwell assay suggested that MDA-MB-453 cells became much less invasive(P<0.01) after being transfected with mi R-455 mimics. During the q RT-PCR, the expression level of MALAT1 declined significantly after transfection(P<0.01). Overexpressed mi R-455 significantly inhibited the proliferation and migration of MDA-MB-453 cells and the expression of MALAT1. We conclude that mi R-455 may be a useful potential biomarker for forecasting lymph node metastasis and the prognosis of Her-2-positive BC patients. mi R-455 may play an important role in lymph node metastasis of BC by interacting with MALAT1.展开更多
Objective:A subset of patients with human epidermal growth factor receptor 2 positive(HER2+)breast cancer shows insensitivity to neoadjuvant therapy(NAT),often evidenced by imaging results indicating stable disease(SD...Objective:A subset of patients with human epidermal growth factor receptor 2 positive(HER2+)breast cancer shows insensitivity to neoadjuvant therapy(NAT),often evidenced by imaging results indicating stable disease(SD)or progressive disease(PD),which may reflect intrinsic resistance to treatment.We aimed to investigate the factors associated with NAT insensitivity and its prognostic value in HER2+breast cancer.Methods:This study included consecutive patients with HER2+breast cancer who received NAT consisting of chemotherapy combined with anti-HER2 monoclonal antibodies.NAT insensitivity was defined as SD or PD on the basis of treatment response evaluations.Statistical analyses were conducted on the collected clinical data,and HER2 heterogeneity was subsequently assessed.Results:A total of 541 patients were included in the study,among whom 63(11.6%)were categorized as NATinsensitive group and 478(88.4%)as NAT-sensitive group.Hormone receptor(HR)status(P=0.033),HER2 status(P=0.036)and anti-HER2 therapy(P=0.007)were associated with NAT sensitivity.NAT-insensitive group had a significantly shorter event-free survival(EFS)(3-year:69.4%vs.94.3%;P<0.001)and remained an independent prognostic factor according to Cox models[hazard ratio(HR)=8.637;95%confidence interval(95%CI),3.091-24.136;P<0.001].Exploratory analysis revealed a greater proportion of HER2 heterogeneity in the NAT-insensitive group(19.4%vs.4.3%;P=0.035).Conclusions:HR positivity,HER22+/fluorescence in situ hybridization(FISH)+status,and trastuzumab monotherapy are associated with NAT insensitivity,and NAT insensitivity independently indicates poor EFS.This study also highlights the need for prospective studies to clarify the role of HER2 heterogeneity and other mechanisms involved in predicting the response to NAT.展开更多
基金Project supported by the Foundation for Key Platform Technological Project of Zhejiang Medical Science and Hygiene(No.2016ZDB003),China。
文摘The aim of this study was to identify some biomarkers for predicting lymph node metastasis and prognosis of human epidermal growth factor receptor 2(Her-2)-positive breast cancer(BC). We analyzed correlations between micro RNAs(mi RNAs) and the prognosis of patients with BC based on data collected from The Cancer Genome Atlas(TCGA) database. The expression levels of mi R-455, mi R-143, and mi R-99 a were measured in clinical samples of Her-2-positive BC patients with different degrees of lymph node metastasis. We investigated the impacts of overexpressed mi R-455 on the proliferation and invasiveness of MDA-MB-453 cells and measured its effects on the expression of long non-coding RNA(lnc RNA) metastasis-associated lung adenocarcinoma transcript 1(MALAT1) by quantitative real-time polymerase chain reaction(q RT-PCR). The expression of mi R-455 was significantly and positively correlated to the prognosis and overall survival(OS) of the BC(P=0.028), according to TCGA information. The expression level of mi R-455 was positively correlated with OS and relapse-free survival(RFS) of patients with Her-2-positive BC, and was negatively correlated with the number of metastatic lymph nodes(P<0.05). Transwell assay suggested that MDA-MB-453 cells became much less invasive(P<0.01) after being transfected with mi R-455 mimics. During the q RT-PCR, the expression level of MALAT1 declined significantly after transfection(P<0.01). Overexpressed mi R-455 significantly inhibited the proliferation and migration of MDA-MB-453 cells and the expression of MALAT1. We conclude that mi R-455 may be a useful potential biomarker for forecasting lymph node metastasis and the prognosis of Her-2-positive BC patients. mi R-455 may play an important role in lymph node metastasis of BC by interacting with MALAT1.
基金supported by the CAMS Innovation Fund for Medical Sciences(CIFMS,No.2021-I2M-1-014,2023-I2M-C&T-B-077 and 2023-I2M-C&T-B-081)the Beijing Natural Science Foundation(No.L258033)the National High Level Hospital Clinical Research Funding(No.2025-LYZX-D-A02)。
文摘Objective:A subset of patients with human epidermal growth factor receptor 2 positive(HER2+)breast cancer shows insensitivity to neoadjuvant therapy(NAT),often evidenced by imaging results indicating stable disease(SD)or progressive disease(PD),which may reflect intrinsic resistance to treatment.We aimed to investigate the factors associated with NAT insensitivity and its prognostic value in HER2+breast cancer.Methods:This study included consecutive patients with HER2+breast cancer who received NAT consisting of chemotherapy combined with anti-HER2 monoclonal antibodies.NAT insensitivity was defined as SD or PD on the basis of treatment response evaluations.Statistical analyses were conducted on the collected clinical data,and HER2 heterogeneity was subsequently assessed.Results:A total of 541 patients were included in the study,among whom 63(11.6%)were categorized as NATinsensitive group and 478(88.4%)as NAT-sensitive group.Hormone receptor(HR)status(P=0.033),HER2 status(P=0.036)and anti-HER2 therapy(P=0.007)were associated with NAT sensitivity.NAT-insensitive group had a significantly shorter event-free survival(EFS)(3-year:69.4%vs.94.3%;P<0.001)and remained an independent prognostic factor according to Cox models[hazard ratio(HR)=8.637;95%confidence interval(95%CI),3.091-24.136;P<0.001].Exploratory analysis revealed a greater proportion of HER2 heterogeneity in the NAT-insensitive group(19.4%vs.4.3%;P=0.035).Conclusions:HR positivity,HER22+/fluorescence in situ hybridization(FISH)+status,and trastuzumab monotherapy are associated with NAT insensitivity,and NAT insensitivity independently indicates poor EFS.This study also highlights the need for prospective studies to clarify the role of HER2 heterogeneity and other mechanisms involved in predicting the response to NAT.
