scholarly journals MiR-324-5P Functions as a Novel Serum Biomarker and Modulates Breast Cancer Malignant Activity

Author(s):  
Jiling Zhang ◽  
Yanyan Zhang ◽  
Shanmei Lv ◽  
Huiying Wang ◽  
Lu Gao ◽  
...  

Abstract Introduction: The best management practices for patients with breast cancer(BC) involve early detection and deterioration prevention. Therefore, it is important to study the occurrence of BC and its development mechanism and explore more sensitive diagnostic and prognostic indicators.Objective: Our study explored the significance and the serum miR-324-5p application in the diagnosis and prognosis of BC and evaluated possible molecular mechanisms.Methods: MiR-324-5p expressions in the serum and tissue of patients with BC were observed by real-time fluorescence quantitative polymerase chain reaction (PCR). Next, the miR-324-5p diagnostic ability in BC was evaluated by the receiver operating characteristic curve. Kaplan-Meier analyzed the relationship between expression of miR-324-5P and prognosis. The Cox regression model evaluated the serum miR-324-5P prognostic value in predicting disease-free survival (DFS) and overall survival (OS). In functional studies, cell counting Kit-8 assay and Cloning experiment were employed to assess BC cells’ proliferation level. Transwell assays and wound healing assays were performed to determine the effect of miR-324-5p on BC cell invasion and migration. In addition, the flow cytometry test was conducted to determine the effect of miR-324-5p on the apoptotic rate of BC cells. Finally, bioinformatics tools were employed to detect the potential target genes of miR-324-5p in BC.Results: miR-324-5p expression is up-regulated in in BC cells, which is related to tumor stage(p=0.0291)and age( p=0.0278). In addition, a BC diagnosis based on serum miR-324-5p levels had an 66% sensitivity, 78% specificity, and the area under the curve was approximately 0.7581. DFS (p=0.027) and OS (p<0.017) in the low miR-324-5P expression group were higher than those in the high expression group. The tumor node metastasis staging、Ki-67 and miR-324-5P were independent prognostic factors for the survival of patients with BC. In addition, miR-324-5p had a positive effect on BC cell invasion and proliferation, thereby preventing apoptosis. Finally, bioinformatics synthesis showed that the miR-324-5p target genes in BC are cysteine-rich hydrophobic domain 1 (CHIC1) and kruppel-like factor 7 (KLF7).Conclusion: MiR-324-5p may perform its oncogenic functions by interacting with the CHIC1 and KLF7 genes, and its existence in serum could serve as a diagnostic and prognostic biomarker of BC.

2020 ◽  
Vol 19 ◽  
pp. 153303382096558
Author(s):  
Lixia Shan ◽  
Tao Zhao ◽  
Yu Wang

Objective: Long non-coding RNAs (lncRNAs) play a critical role in tumorigenesis. Upregulation of lncRNA deleted in lymphocytic leukemia 1 (DLEU1) has been reported in endometrial cancer (EC) tissues. This prospective study aimed to determine the potential clinical significance of serum lncRNA DLEU1 in EC. Methods: The serum lncRNA DLEU1 level was detected in EC patients, patients with endometrial hyperplasia and healthy controls by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Then its clinical value in EC was further evaluated. Results: Our results demonstrated that serum lncRNA DLEU1 levels were significantly increased in patients with EC, and serum lncRNA DLEU1 showed good performance for discriminating EC patients from patients with endometrial hyperplasia and healthy controls. In addition, EC patients with advanced clinicopathological features had higher circulating lncRNA DLEU1 level than those with favorable clinical characteristics. Moreover, EC patients in the high serum lncRNA DLEU1 group suffered worse overall survival and disease-free survival than those in the low serum lncRNA DLEU1 group. Furthermore, multivariate cox regression analysis displayed that the serum lncRNA DLEU1 served as an independent prognostic factor for EC. Conclusions: Collectively, our study suggests that serum lncRNA DLEU1 is a novel and promising biomarker for prognostic estimation of EC.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Keunyoung Kim ◽  
In-Joo Kim ◽  
Kyoungjune Pak ◽  
Taewoo Kang ◽  
Young Mi Seol ◽  
...  

Abstract Background This study aimed to evaluate the potential of metabolic activity of the psoas muscle measured by 18F-fluorodeoxyglucose positron emission tomography-computed tomography to predict treatment outcomes in patients with resectable breast cancer. Methods The medical records of 288 patients who had undergone surgical resection for stages I–III invasive ductal carcinoma of the breast between January 2014 and December 2014 in Pusan National University Hospital were reviewed. The standardized uptake values (SUVs) of the bilateral psoas muscle were normalized using the mean SUV of the liver. SUVRmax was calculated as the ratio of the maximum SUV of the average bilateral psoas muscle to the mean SUV of the liver. SUVRmean was calculated as the ratio of the mean SUV of the bilateral psoas muscle to the mean SUV of the liver. Results Univariate analyses identified a higher T stage, higher N stage, estrogen receptor negativity, progesterone receptor negativity, human epidermal growth factor receptor 2 positivity, triple-negative breast cancer, mastectomy (rather than breast-conserving surgery), SUVRmean > 0.464, and SUVRmax > 0.565 as significant adverse factors for disease-free survival (DFS). Multivariate Cox regression analysis revealed that N3 stage (hazard ratio [HR] = 5.347, P = 0.031) was an independent factor for recurrence. An SUVRmax > 0.565 (HR = 4.987, P = 0.050) seemed to have a correlation with shorter DFS. Conclusions A higher SUVRmax of the psoas muscle, which could be a surrogate marker of insulin resistance, showed strong potential as an independent prognostic factor for recurrence in patients with resectable breast cancer.


2021 ◽  
Author(s):  
Ouissam Al Jarroudi ◽  
Khalid El Bairi ◽  
Naima Abda ◽  
Adil Zaimi ◽  
Laila Jaouani ◽  
...  

Background: Inflammatory breast cancer (IBC) is uncommon, aggressive and associated with poor survival outcomes. The lack of prognostic biomarkers and therapeutic targets specific to IBC is an added challenge for clinical practice and research. Inflammatory biomarkers such as neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios (NLR and PLR) demonstrated independent prognostic impact for survival in breast cancer. In our study, these biomarkers were investigated in a cohort of patients with nonmetastatic IBC. Methods: A retrospective cohort of 102 IBC patients with nonmetastatic disease was conducted at the Mohammed VI University Hospital (Oujda, Morocco) between January 2010 and December 2014. NLR and PLR were obtained from blood cell count at baseline before neoadjuvant chemotherapy (NACT) from patients’ medical records. The receiver operating characteristic was used to find the optimal cut-off. Correlation between these blood-based biomarkers and response to NACT was analyzed by Chi-squared and Fisher's exact test. Their prognostic value for predicting disease-free survival (DFS) and overall survival (OS) was performed based on Cox regression models. Results: Totally, 102 patients with IBC were included in the analysis. Pathologic complete response (pCR) after NACT, defined by the absence of an invasive tumor in the breast tissues and nodes after surgery (ypT0 ypN0), was observed in eight patients (7.8%). NACT response was found to be associated with menopausal status (p = 0.039) and nodal status (p < 0.001). Patients with a low NLR had a higher pCR rate as compared with the high-NLR group (p = 0.043). However, the pCR rate was not significantly associated with age (p = 0.122), tumor side (p = 0.403), BMI (p = 0.615), histological grade (p = 0.059), hormone receptors status (p = 0.206), human epidermal growth factor receptor 2 (p = 0.491) and PLR (p = 0.096). Pre-treatment blood-based NLR of 2.28 was used as the cut-off value to discriminate between high and low NLR according to the receiver operating characteristic curves. Similarly, a value of 178 was used as the cut off for PLR. Patients with low-NLR had a significantly better 5-year DFS (p < 0.001) and OS (p < 0.001) than the high-NLR group. Moreover, low-PLR was significantly associated with higher DFS (p = 0.001) and OS (p = 0.003). The NLR showed a significant prognostic impact for DFS (HR: 2.57; 95% CI: 1.43–4.61; p = 0.01) and for OS (HR: 2.92; 95% CI: 1.70–5.02; p < 0.001). Similarly, a meaningful association between PLR and 5-year DFS (HR: 1.95; 95% CI: 1.10–3.46; p = 0.021) and OS (HR: 1.82; 95% CI: 1.06–3.14; p = 0.03) was noticed. Conclusions: High NLR and PLR were found associated with reduced DFS and OS in nonmetastatic IBC. Further studies are awaited to confirm these findings.


2018 ◽  
pp. 1-12 ◽  
Author(s):  
Scooter Willis ◽  
Varvara Polydoropoulou ◽  
Yuliang Sun ◽  
Brandon Young ◽  
Zoi Tsourti ◽  
...  

Purpose The Herceptin Adjuvant study is an international multicenter randomized trial that compared 1 or 2 years of trastuzumab given every 3 weeks with observation in women with human epidermal growth factor 2–positive (HER2+) breast cancer after chemotherapy. Identification of biomarkers predictive of a benefit from trastuzumab will minimize overtreatment and lower health care costs. Methods To identify possible single-gene biomarkers, an exploratory analysis of 3,669 gene probes not expected to be expressed in normal breast tissue was conducted. Disease-free survival (DFS) was used as the end point in a Cox regression model, with the interaction term between C8A mRNA and treatment as a categorical variable split on the cohort mean. Results A significant interaction between C8A mRNA and treatment was detected ( P < .001), indicating a predictive response to trastuzumab treatment. For the C8A-low subgroup (mRNA expression lower than the cohort mean), no significant treatment benefit was observed ( P = .73). In the C8A-high subgroup, patients receiving trastuzumab experienced a lower hazard of a DFS event by approximately 75% compared with those in the observation arm (hazard ratio [HR], 0.25; P < .001). A significant prognostic effect of C8A mRNA also was seen ( P < .001) in the observation arm, where the C8A-high group hazard of a DFS event was three times the respective hazard of the C8A-low group (HR, 3.27; P < .001). C8A mRNA is highly prognostic in the Hungarian Academy of Science HER2+ gastric cancer cohort (HR, 1.72; P < .001). Conclusion C8A as a single-gene biomarker prognostic of DFS and predictive of a benefit from trastuzumab has the potential to improve the standard of care in HER2+ breast cancer if validated by additional studies. Understanding the advantage of overexpression of C8A related to the innate immune response can give insight into the mechanisms that drive cancer.


2018 ◽  
Vol 49 (3) ◽  
pp. 961-970 ◽  
Author(s):  
Peng Xing ◽  
Huiting Dong ◽  
Qun Liu ◽  
Tingting Zhao ◽  
Fan Yao ◽  
...  

Background/Aims: This study aimed to explore the prognostic value of aldehyde dehydrogenase 1 (ALDH1) expression and vasculogenic mimicry (VM) in patients with breast cancer. Methods: ALDH1 expression and the presence of VM were examined by immunohistochemistry and CD31/PAS double staining, respectively, using formalin-fixed paraffin-embedded tissues from 202 breast cancer patients. The mean follow-up period ranged from 15 to 115 months. The Kaplan-Meier method was used to plot survival curves. Prognostic values were assessed by multivariate analysis using the Cox regression model. Results: ALDH1 expression was strongly associated with VM (P = 0.005). ALDH1 expression was positively correlated with histological grade (P = 0.011). Both ALDH1 expression and VM were negatively related to the status of the estrogen receptor and progesterone receptor and were statistically increased in triple-negative breast cancer. Patients with ALDH1 expression or VM displayed poorer disease-free survival (DFS) and overall survival (OS) than ALDH1-negative or VM-negative patients, with the worst OS and DFS observed in ALDH1/VM-double-positive patients. ALDH1-positive and VM-positive were independent survival risk factors for DFS and OS. Conclusion: ALDH1 expression and VM are correlated with the survival rate of patients with breast cancer. ALDH1 and VM, either alone or together, are prognostic factors in patients with breast cancer.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 596-596
Author(s):  
P. P. Gor ◽  
R. J. Gray ◽  
M. Horn ◽  
T. R. Rebbeck ◽  
P. A. Gimotty ◽  
...  

596 Background: Disparate outcomes of breast cancer patients after adjuvant chemotherapy may be influenced by variation in drug metabolism due to genetic polymorphisms in DME. Cyclophosphamide and thiotepa require activation by cytochrome P450 (CYP) and detoxification by glutathione-S-transferase, two highly polymorphic enzymes. We hypothesized that variants in CYP3A4(*1B), GSTM1 and GSTT1 would impact survival outcomes after adjuvant chemotherapy, with effects potentially modulated by chemotherapy dose. Methods: We performed a retrospective cohort study of patients enrolled on E2190/Int0121, a randomized trial of cyclophosphamide (C), doxorubicin (A), and fluorouracil (F) versus CAF + high dose chemotherapy (HDC) using cyclophosphamide and thiotepa followed by stem cell rescue; disease-free survival (DFS) and overall survival (OS) were equivalent in the clinical trial. PCR-based methods were used to genotype hematologic stem cells. Hazard ratios for genotypes were obtained using Cox regression. Results: Stem cell samples and clinical data from August 1, 1991 through August 1, 2005 were available for 347/540 of patients enrolled; 151 patients on CAF and 196 on CAF + HDC arms, respectively. Median follow-up was 9.8 years. See table . CYP3A4*1B allele carriers had significantly poorer DFS (HR 1.84) in the combined cohort and CAF arm (HR 1.87), but not in the HDC arm; OS was not significant by CYP3A4 genotype. GSTM1 null homozygotes in the combined cohort and HDC arm had significantly better DFS (HR 0.70 and 0.66, respectively) and OS (HR 0.67 and 0.57, respectively), but not in the CAF arm. GSTT1 null homozygotes had significantly worse DFS (HR 2.3) and OS (2.02) in the CAF arm, but not in the HDC arm or combined cohort. Conclusions: In the overall E2190/Int0121 cohort, polymorphisms in activating (CYP3A4*1B) and inactivating (GSTM1) DME significantly impact DFS and OS. The detrimental effect of GSTT1 in the CAF arm appears to be ameliorated by HDC. [Table: see text] No significant financial relationships to disclose.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 571-571 ◽  
Author(s):  
Sibylle Loibl ◽  
Gustavo Werutsky ◽  
Valentina Nekljudova ◽  
Sabine Seiler ◽  
Jens Uwe Blohmer ◽  
...  

571 Background: Time interval from diagnostic biopsy to neoadjuvant chemotherapy (NACT) start (TBC) and from last chemotherapy application to surgery (TCS) are influenced by many factors. It is unclear whether a delay of systemic therapy or surgery impacts patients (pts) outcome. Methods: 9127 pts with early BC from 6 German neoadjuvant trials receiving an anthracycline-taxane based NACT were included. pCR (ypT0/is ypN0), disease free survival (DFS) and overall survival (OS) were compared according to TBC and TCS length (cut-off of ≤4 vs >4weeks (w)), overall and in subgroups (BC subtypes [luminal, HER2+, triple-negative breast cancer (TNBC)] and pCR [yes vs no] for survival endpoints) adjusted by study. Results: Data on TBC were available for 8072 pts, on TCS for 6420, on follow-up (FU) for 7889. Median age was 49 yrs, 25.6% had cT3-4, 48.6% N+, 44.1% G3, 46.0% luminal, 26.4% TNBC, 27.6% HER2+ tumors. Median (m) FU-time was 65 months [0-201]. mTBC was 23 days [0-228] (67.5% ≤4w vs 32.5% >4w), mTCS was 28d [0-204] (53.7% ≤4w vs 46.3% >4w), with inter-study variability for mTBC ranging from 14 to 32d and for mTCS ranging from 24 to 29d from the oldest to the most recently conducted study. TBC did not influence the pCR rate, neither in all patients nor in subgroups. At multivariable logistic regression analysis TBC length did not independently predict pCR. TBC did not influence DFS or OS, neither in all patients nor in subgroups. TCS<4w was associated with a trend towards a better DFS in all patients (HR=1.11 95%CI (0.99-1.24), p=0.08) and in pts not achieving pCR (HR=1.12, 95%CI (0.99-1.26), p=0.08). No difference was observed within BC subtypes. OS was not impacted by TCS length. At multivariable Cox regression analysis TBC or TCS≤4 vs >4w did not independently influence DFS or OS. Conclusions: A delay in starting NACT does not impact the pCR rate, DFS or OS and results are independent of the subgroup. However, early surgery after NACT in pts without pCR seems to influence outcome. Our analysis is explorative, but indicates for the first time, that time interval of starting NACT and undergoing surgery might be uncritical. Further research is ongoing.


2022 ◽  
Author(s):  
Meng Luo ◽  
Huihui Chen ◽  
Hao Deng ◽  
Yao Jin ◽  
Gui Wang ◽  
...  

Abstract PurposePostmastectomy radiotherapy (PMRT) after NAC in breast cancer patients with initial clinical stage cT1−2N+, especially for those who achieved ypT1−2N0, is still controversial. This study was to evaluate the survival prognosis of cT1−2N+ patients after NAC with or without PMRT, and to discuss the selection of patients who may omit PMRT.Patients and MethodsFrom January 2005 to December 2017, 3055 female breast cancer patients underwent mastectomy in our medical center, among whom 215 patients of cT1−2N+ stage, receiving neoadjuvant chemotherapy (NAC) with or without PMRT were finally analyzed. The median follow-up duration was 72.6 months. The primary endpoint was overall survival, and the secondary endpoint was disease-free survival. Comparison was conducted between PMRT and non-PMRT subgroups.ResultsOf the 215 eligible patients, 35.8% (77/215) cT1−2N+ patients achieved ypT0−2N0 after NAC while 64.2% (138/215) of the patients remained nodal positive (ypT0−2N+). The 5-year DFS of ypT0−2N0 non-PMRT was 79.5% (95% confidence interval [CI] 63.4-95.6%). No statistically significant difference was observed between the ypT0−2N0 PMRT and non-PMRT subgroups for the 5-year DFS (78.5% vs 79.5%, p = 0.673) and OS (88.8% vs 90.8%, p = 0.721). The 5-years DFS didn’t obviously differ between the ypT0−2N0 non-PMRT subgroup and cT1−2N0 subgroup (79.5% vs 93.3%, p = 0.070). By using Cox regression model in multivariate analyses of prognosis in ypT0−2N+ PMRT subgroup, HER2 overexpression and triple-negative breast cancer were significantly poor predictors of DFS and OS, while ypN stage was significant independent predictors of OS.ConclusionAn excellent response to NAC (ypT0−2N0) indicates a sufficiently favorable prognosis, and PMRT might be omitted for cT1−2N+ breast cancer patients with ypT0−2N0 after NAC.


2021 ◽  
Vol 11 ◽  
Author(s):  
Li Chen ◽  
Xiuzhi Zhu ◽  
Boyue Han ◽  
Lei Ji ◽  
Ling Yao ◽  
...  

PurposeMicroRNAs can influence many biological processes and have shown promise as cancer biomarkers. Few studies have focused on the expression of microRNA-223 (miR-223) and its precise role in breast cancer (BC). We aimed to examine the expression level of miR-223 and its prognostic value in BC.MethodsTissue microarray (TMA)-based miRNA detection in situ hybridization (ISH) with a locked nucleic acid (LNA) probe was used to detect miR-223 expression in 450 BC tissue samples. Overall survival (OS) and disease-free survival (DFS) were compared between two groups using the Kaplan-Meier method and Cox regression model.ResultsOS and DFS were prolonged in the high miR-223 expression group compared to the low miR-223 expression group (p &lt; 0.0001 and p = 0.017, respectively), especially in patients with the triple-negative breast cancer (TNBC) subtype (p = 0.046 and p &lt; 0.001, respectively). Univariate and multivariate Cox regression analyses revealed that TNM stage (p = 0.008), the molecular subtype (p = 0.049), and miR-223 (p &lt; 0.001) were independently associated with OS and DFS. External validation was performed with the METABRIC and The Cancer Genome Atlas (TCGA) databases via online webtools and was consistent with the data described above.ConclusionsThis study provides evidence that high miR-223 expression at diagnosis is associated with improved DFS and OS for BC patients, especially those with the TNBC subtype. miR-223 is a valid and independent prognostic biomarker in BC.


2021 ◽  
Author(s):  
Yuhao Xu ◽  
Yaoqiang Du ◽  
Qinghui Zheng ◽  
Hongchao Tang ◽  
Yangyang Qian ◽  
...  

Abstract Background Recent years, the breast cancer became the most commonly diagnosed cancer. The use of neoadjuvant chemotherapy (NACT) makes a significant contribution to chemotherapy in breast cancer. We aimed to develop the novel model as a predictor of distant relapse-free survival (DRFS) in breast cancer patients receiving taxane and anthracycline-based NACT. Methods We collected the mRNA expression datasets of patients from GSE25055 and GSE25065 in Gene Expression Omnibus (GEO). Univariate and Multivariate Cox Regression Analyses were conducted to achieve the prognostic genes that associated with DRFS. Moreover, the E2F targets genes were obtained from GSEA. We obtained the intersection genes between the prognostic genes and E2F target genes, then validated in GSE32603 dataset. And we established a nomogram model based on PTTG1 expression level and several clinical characteristics. Results A novel nomogram was conducted. The receiver operating characteristic (AUC = 0.849), C-index (0.805) and calibration plots were applied to assess the effect of this model. Conclusion Our study found that the E2F target genes, such as the PTTG1 may serve as a potential biomarker in breast cancer, and provided superior estimation of DRFS, which can guide the clinical practice in NACT of breast cancer.


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