scholarly journals DNAJC3-AS1 Is Associated with Proliferation, Metastasis, and Poor Prognosis of Breast Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Yi Zhang ◽  
Jing-jing Li ◽  
Bo Luo ◽  
Xiao-fei Guo ◽  
Jian-xin Liu ◽  
...  

Objective. Long noncoding RNA DNAJC3-AS1 (DNAJC3-AS1) was a newly identified tumor-related lncRNA. The aim of the present study was to explore the prognostic value and diagnostic of DNAJC3-AS1 (DNAJC3-AS1) expression in breast cancer (BC) patients. Patients and Methods. The expression of DNAJC3-AS1 was detected in 170 BC tissues and matched normal breast samples by qRT-PCR. The diagnostic value of DNAJC3-AS1 was examined by receiver-operating characteristic (ROC) assays. The correlation of DNAJC3-AS1 with clinicopathological features and prognosis was also statistically analyzed. CCK-8 assays, colony formation assays, and Transwell assays were applied to examine the potential function of DNAJC3-AS1 on tumor progression. Western blot was used to examine the expression of EMT-related proteins. Results. The expression of DNAJC3-AS1 in BC specimens was higher than that in the adjacent nontumor tissues ( p < 0.01 ). Diagnostic assays revealed that DNAJC3-AS1 has considerable diagnostic accuracy, with an area under the ROC curve (AUC) of 0.7457 ( p < 0.001 ). High DNAJC3-AS1 expression was positively associated with lymph node metastasis ( p = 0.010 ) and clinical stage ( p = 0.023 ). A survival study revealed that patients with high DNAJC3-AS1 expression had shorter overall survival ( p = 0.0067 ) and disease-free survival ( p < 0.0001 ) than those with low DNAJC3-AS1 expression. More importantly, multivariate assays indicated that DNAJC3-AS1 was an independent prognostic factor in BC patients. Functional assays confirmed that silence of DNAJC3-AS1 distinctly suppressed the proliferation, metastasis, and EMT progress of BC cells. Conclusions. DNAJC3-AS1 may be a prognostic and diagnostic biomarker for BC patients.

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yanyu Zhang ◽  
Yaotian Zhang ◽  
Zhuang Liu ◽  
Zilan Qin ◽  
Yubing Li ◽  
...  

Background. The impact of postmastectomy radiotherapy (PMRT) in patients receiving neoadjuvant chemotherapy (NAC) is unclear. The purpose of this study is to identify the patients who may benefit from PMRT. Methods. We retrospectively analysed patients with clinical stage II-III breast cancer who underwent NAC and modified radical mastectomy at our centre from 2007 to 2015. We investigated the relationship amongst locoregional recurrence rate (LRR), disease-free survival (DFS), and clinical pathological characters. Results. A total of 554 patients were analysed in this study. The median follow-up time was 65 months. Amongst the patients, 58 (10.5%) had locoregional recurrence, 138 (24.9%) had distant metastasis, and 72 (13.0%) patients died. The 5-year cumulative incidence of LRR and DFS was 9.2% and 74.2%, respectively. A total of 399 (72%) patients received PMRT and 155 (28%) did not. The 5-year LRR of the patients with PMRT (7.3% vs. 14.1%, P = 0.01 ) decreased significantly. We found that PMRT was an independent prognostic factor of LRR and DFS. Patients with the persistent involvement of 1–3 lymph nodes (ypN1) and more than 4 positive lymph nodes (ypN2-3) had a better outcome after PMRT than those without. However, the LRR and DFS of patients with negative lymph nodes at the time of surgery (ypN0) and who received PMRT showed no significant benefits. Amongst all patients with the three molecular subtypes of breast cancer, patients with triple-negative breast cancer had the highest pathological complete response rate but the worst prognosis ( P = 0.001 ). Conclusion. Results showed that PMRT significantly reduced the LRR of patients with clinical stage II-III breast cancer after receiving NAC and mastectomy. YpN0 patients derived no local control or survival benefit after receiving PMRT, whereas those with ypN1 and ypN2-3 could obviously benefit from PMRT.


2017 ◽  
Vol 35 (23) ◽  
pp. 2639-2646 ◽  
Author(s):  
Bent Ejlertsen ◽  
Malgorzata K. Tuxen ◽  
Erik Hugger Jakobsen ◽  
Maj-Britt Jensen ◽  
Ann Soegaard Knoop ◽  
...  

Purpose Administration of anthracycline and taxane therapy in the adjuvant setting is considered a standard for breast cancer. We evaluated a non–anthracycline-based regimen in TOP2A-normal patients. Patients and Methods In this multicenter, open-label, phase III trial, 2,012 women with early TOP2A-normal breast cancer and at least one high-risk factor were randomly assigned to receive six cycles of docetaxel (75 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks (DC) or three cycles of epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) followed by three cycles of docetaxel (100 mg/m2; EC-D). The primary end point was disease-free survival (DFS) after a median of 5 years of follow-up. Secondary end points were patient-reported toxicity, overall survival (OS), and distant disease–free survival. Results At a median estimated potential follow-up of 69 months, 5-year DFS was 87.9% (95% CI, 85.6% to 89.8%) in the EC-D arm and 88.3% (95% CI, 86.1% to 90.1%) in the DC arm. There was no significant difference in the risk of DFS events (hazard ratio [HR], 1.00; 95% CI, 0.78 to 1.28; P = 1.00), distant disease–free survival (HR, 1.12; 95% CI, 0.86 to 1.47; P = .40), or mortality (HR, 1.15; 95% CI, 0.83 to 1.59; P = .41) in the intent-to-treat analysis. A significant interaction between menopausal status and treatment group was observed for DFS ( P = .04) but not for OS ( P = .07). Patients with grade 3 tumors derived most benefit from DC, and patients with grade 1 to 2 tumors derived most benefit from EC-D (DFS: interaction P = .02; and OS: interaction P = .03). Patients receiving EC-D reported significantly more stomatitis, myalgia or arthralgia, vomiting, nausea, fatigue, and peripheral neuropathy, whereas edema was more frequent after DC. Conclusion This study provides evidence to support no overall outcome benefit from adjuvant anthracyclines in patients with early TOP2A-normal breast cancer.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hanfang Jiang ◽  
Huiping Li

Abstract Background Breast cancer (BC) is a leading cause of cancer-related death in females worldwide. Previous studies have demonstrated that matrix metalloproteinases (MMPs) play key roles in metastasis and are associated with survival in various cancers. The prognostic values of MMP2 and MMP9 expression in BC have been investigated, but the results remain controversial. Thus, we performed the present meta-analysis to investigate the associations between MMP2/9 expressions in tumor cells with clinicopathologic features and survival outcome in BC patients. Methods Eligible studies were searched in PubMed, Web of Science, EMBASE, CNKI and Wanfang databases. The associations of MMP2/9 overexpression in tumor cells with overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS) were assessed by hazard ratio (HR) and 95% confidence interval (CI). The associations of MMP2/9 overexpression with clinicopathological features were investigated by calculating odds ratio (OR) and 95% CI. Subgroup analysis, sensitivity analysis, meta-regression, and analysis for publication bias were performed. Results A total of 41 studies comprising 6517 patients with primary BC were finally included. MMP2 overexpression was associated with an unfavorable OS (HR = 1.60, 95% CI 1.33 –1.94, P < 0.001) while MMP9 overexpression predicted a shorter OS (HR = 1.52, 95% CI 1.30 –1.77, P < 0.001). MMP2 overexpression conferred a higher risk to distant metastasis (OR = 2.69, 95% CI 1.35–5.39, P = 0.005) and MMP9 overexpression correlated with lymph node metastasis (OR = 2.90, 95% CI 1.86 – 4.53, P < 0.001). Moreover, MMP2 and MMP9 overexpression were both associated with higher clinical stage and histological grade in BC patients. MMP9 overexpression was more frequent in patients with larger tumor sizes. Conclusions Tumoral MMP2 and MMP9 are promising markers for predicting the prognosis in patients with BC.


Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3303
Author(s):  
Debora Macis ◽  
Valentina Aristarco ◽  
Harriet Johansson ◽  
Aliana Guerrieri-Gonzaga ◽  
Sara Raimondi ◽  
...  

Adiponectin and leptin are adipokines secreted by the adipose tissue that are associated with several chronic diseases including cancer. We aimed to compare the immunoassay platform ELLA with an enzyme-linked immunosorbent assay (ELISA) kit and to assess whether the results of the association analyses with breast cancer risk were dependent on the assay used. We measured adiponectin and leptin with ELLA and ELISA on baseline serum samples of 116 Italian postmenopausal women enrolled in two international breast cancer prevention trials. Results were compared with Deming, Passing–Bablok regression and Bland–Altman plots. Disease-free survival was analyzed with the Cox model. There was a good correlation between the methods for adiponectin and leptin (r > 0.96). We found an increased breast cancer risk for very low adiponectin levels (HR for ELLA = 3.75; 95% CI: 1.37;10.25, p = 0.01), whereas no significant association was found for leptin levels. The disease-free survival curves were almost identical for values obtained with the two methods, for both biomarkers. The ELLA platform showed a good concordance with ELISA for adiponectin and leptin measurements. Our results support the association of very low adiponectin levels with postmenopausal breast cancer risk, irrespective of the method used. The ELLA platform is a time-saving system with high reproducibility, therefore we recommend its use for biomarker assessment.


2021 ◽  
pp. 172460082110111
Author(s):  
Erika Korobeinikova ◽  
Rasa Ugenskiene ◽  
Ruta Insodaite ◽  
Viktoras Rudzianskas ◽  
Jurgita Gudaitiene ◽  
...  

Background: Genetic variations in oxidative stress-related genes may alter the coded protein level and impact the pathogenesis of breast cancer. Methods: The current study investigated the associations of functional single nucleotide polymorphisms in the NFE2L2, HMOX1, P21, TXNRD2, and ATF3 genes with the early-stage breast cancer clinicopathological characteristics and disease-free survival, metastasis-free survival, and overall survival. A total of 202 Eastern European (Lithuanian) women with primary I–II stage breast cancer were involved. Genotyping of the single nucleotide polymorphisms was performed using TaqMan single nucleotide polymorphisms genotyping assays. Results: The CA+AA genotypes of P21 rs1801270 were significantly less frequent in patients with lymph node metastasis and larger tumor size ( P=0.041 and P=0.022, respectively). The TT genotype in ATF3 rs3125289 had significantly lower risk of estrogen receptor (ER), progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) positive status ( P=0.023, P=0.046, and P=0.040, respectively). In both, univariate and multivariate Cox analysis, TXNRD2 rs1139793 GG genotype vs. GA+AA was a negative prognostic factor for disease-free survival (multivariate hazard ratio (HR) 2.248; P=0.025) and overall survival (multivariate HR 2.248; P=0.029). The ATF3 rs11119982 CC genotype in the genotype model was a negative prognostic factor for disease-free survival (multivariate HR 5.878; P=0.006), metastasis-free survival (multivariate HR 4.759; P=0.018), and overall survival (multivariate HR 3.280; P=0.048). Conclusion: Our findings suggest that P21 rs1801270 is associated with lymph node metastasis and larger tumor size, and ATF3 rs3125289 is associated with ER, PR, and HER2 status. Two potential, novel, early-stage breast cancer survival biomarkers, TXNRD2 rs1139793 and ATF3 rs11119982, were detected. Further investigations are needed to confirm the results of the current study.


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