Mammographically detected breast clustered microcalcifications localized by chest thin-section computed tomography.

BACKGROUND: To explore the capability and clinical significance of chest thin-section computed tomography (CT) for localization of mammographically detected clustered microcalcifications. METHODS: A total of 69 patients with 71 mammographically detected clustered microcalcifications received surgical biopsy under the guidance of mammography (MG), CT was used to localize calcifications combined with MG if calcifications can be seen on CT. Intraoperative mammography of the specimens were performed in all cases for identification of the resected microcalcifications. The clinical, imaging and pathological information of these patients were analyzed. RESULTS: A total of 42 (59.15%) cases of calcifications were localized by CT + MG, 29 (40.85%) cases were guided only by the mammography. All suspicious calcifications on the mammography were successfully removed. Pathological results showed 42 cases were cancer, 23 cases were benign, and 6 cases were atypical hyperplasia. The mean age in the CT + MG group was older than that of the MG group (54.12 vs. 49.27 years; P = 0.014). The maximum diameter of clusters of microcalcifications on mammography in the CT + MG group was larger than that of the MG group [(cranio-caudal view, 1.52 vs. 0.61 mm, P = 0.000; mediolateral oblique (MLO) view, 1.53 vs. 0.62 mm, P = 0.000)]. The gray value ratio (calcified area / paraglandular; MLO, P = 0.004) and the gray value difference (calcified area - paraglandular; MLO, P = 0.005) in the CT + MG group was higher than that of the MG group. Multivariate analysis showed that the max diameter of clusters of microcalcifications (MLO view) was a significant predictive factor of localization by CT in total patients (P = 0.001). CONCLUSIONS: About half of the mammographically detected clustered microcalcifications could be localized by thin-section CT. Maximum diameter of clusters of microcalcifications (MLO view) was a predictor of visibility of calcifications by CT. Chest thin-section CT may be useful for localization of calcifications in some patients, especially for calcifications that are only visible in one view on the mammography.

Identification and verification of immune-related gene prognostic signature based on ssGSEA for breast cancer.

Introduction: Breast cancer (BC) is the most common cancer in women worldwide and has a high mortality rate. The fact that the tumor microenvironment affects clinical outcomes of all types of cancers underlines the involvement of various immune-related genes (IRGs). Therefore, this study aimed to establish an IRGs-based signature for the prognosis of BC patients. Material and methods: In this study, 12 immune cell infiltrating degrees in 1,102 BC cases from The Cancer Genome Atlas (TCGA) database were assessed, and RNA-sequencing (RNA-seq) data of these samples were analyzed by single-sample gene set enrichment analysis (ssGSEA). Based on the results, high, low, and middle immune infiltrating clusters were constructed. A total of 138 overlapped differentially expressed genes (DEGs) were identified in the high and low infiltrating clusters, as well as in normal and BC samples. Univariate Cox regression and LASSO analyses were also performed. Furthermore, GSEA suggested some highly enriched pathways in the different immune infiltrating clusters, leading to a better understanding of potential mechanisms of immune infiltration in BC. Results: Finally, 19 immune-related genes were identified that could be utilized as a potential prognostic biomarker for BC. Kaplan-Meier plot and ROC curve, univariate as well as multivariate Cox analyses were carried out, which suggested that the 19-IRG-based signature is a significant prognosis factor independent of clinical features. Based on the analysis of protein-protein interactions (PPI), the three hub genes were identified. Conclusions: These results provide a new method to predict the prognosis and survival of BC based on the three genes' features.

Construction and analysis of a survival-associated competing endogenous RNA network in breast cancer.

Background: Recently, increasing studies have shown that non-coding RNAs are closely associated with the progression and metastasis of cancer by participating in competing endogenous RNA (ceRNA) networks. However, the role of survival-associated ceRNAs in breast cancer (BC) remains unknown. Methods: The Gene Expression Omnibus database and The Cancer Genome Atlas BRCA_dataset were used to identify differentially expressed RNAs. Furthermore, circRNA-miRNA interactions were predicted based on CircInteractome, while miRNA-mRNA interactions were predicted based on TargetScan, miRDB, and miRTarBase. The survival-associated ceRNA networks were constructed based on the predicted circRNA-miRNA and miRNA-mRNA pairs. Finally, the mechanism of miRNA-mRNA pairs was determined. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of survival-related mRNAs were performed using the hypergeometric distribution formula in R software.The prognosis of hub genes was confirmed using gene set enrichment analysis. Results: Based on the DE-circRNAs of the top 10 initial candidates, 162 DE-miRNAsand 34 DE-miRNAs associated with significant overall survival were obtained. The miRNA target genes were then identified using online tools and verified using the Cancer Genome Atlas (TCGA) database. Overall, 46 survival-associated DE-mRNAs were obtained. The results of GO and KEGG pathway enrichment analyses implied that up-regulated survival-related DE-mRNAs were mostly enriched in the "regulation of cell cycle" and "chromatin" pathways, while down-regulated survival-related DE-mRNAs were mostly enriched in "negative regulation of neurotrophin TRK receptor signaling" and "interleukin-6 receptor complex" pathways. Finally, the survival-associated circRNA-miRNA-mRNA ceRNA network was constructed using 34 miRNAs, 46 mRNAs, and 10 circRNAs. Based on the PPI network, two ceRNA axes were identified. These ceRNA axescould be considered biomarkers for BC.GSEA results revealed that the hub genes were correlated with "VANTVEER_BREAST_CANCER_POOR_PROGNOSIS", and the hub genes were verified using BC patients' tissues. Conclusions: In this study, we constructed a circRNA-mediated ceRNA network related to BC. This network provides new insight into discovering potential biomarkers for diagnosing and treating BC.

Integrated transcriptome and network analysis identifies EZH2/CCNB1/PPARG as prognostic factors in breast cancer.

Breast cancer (BC) has high morbidity, with significant relapse and mortality rates in women worldwide. Therefore, further exploration of its pathogenesis is of great significance. This study selected therapy genes and possible biomarkers to predict BC using bioinformatic methods. To this end, the study examined 21 healthy breasts along with 457 BC tissues in two Gene Expression Omnibus (GEO) datasets and then identified differentially expressed genes (DEGs). Survival-associated DEGs were screened using the Kaplan-Meier curve. Based on Gene Ontology (GO) annotation, survival-associated DEGs were mostly associated with cell division and cellular response to hormone stimulus. The enriched Kyoto Encyclopedia of Gene and Genome (KEGG) pathway was mostly correlated with cell cycle and tyrosine metabolism. Using overlapped survival-associated DEGs, a survival-associated PPI network was constructed. PPI analysis revealed three hub genes (EZH2, CCNB1, and PPARG) by their degree of connection. These hub genes were confirmed using The Cancer Genome Atlas (TCGA)-BRCA dataset and BC tissue samples. Through Gene Set Enrichment Analysis (GSEA), the molecular mechanism of the potential therapy and prognostic genes were evaluated. Thus, hub genes were shown to be associated with KEGG_CELL_CYCLE and VANTVEER_BREAST_CANCER_POOR_PROGNOSIS gene sets. Finally, based on integrated bioinformatics analysis, this study identified three hub genes as possible prognostic biomarkers and therapeutic targets for BC. The results obtained further understanding of the underground molecular mechanisms related to BC occurrence and prognostic outcomes.

Identification of candidate biomarkers correlated with poor prognosis of breast cancer based on bioinformatics analysis.

Breast cancer (BC) is a malignancy with high incidence among women in the world. This study aims to screen key genes and potential prognostic biomarkers for BC using bioinformatics analysis. Total 58 normal tissues and 203 cancer tissues were collected from three Gene Expression Omnibus (GEO) gene expression profiles, and then the differential expressed genes (DEGs) were identified. Subsequently, the Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway were analyzed to investigate the biological function of DEGs. Additionally, hub genes were screened by constructing a protein-protein interaction (PPI) network. Then, we explored the prognostic value and molecular mechanism of these hub genes using Kaplan-Meier (KM) curve and Gene Set Enrichment Analysis (GSEA). As a result, 42 up-regulated and 82 down-regulated DEGs were screened out from GEO datasets. The DEGs were mainly related to cell cycles and cell proliferation by GO and KEGG pathway analysis. Furthermore, 12 hub genes (FN1, AURKA, CCNB1, BUB1B, PRC1, TPX2, NUSAP1, TOP2A, KIF20A, KIF2C, RRM2, ASPM) with a high degree were identified initially, among which, 11 hub genes were significantly correlated with the prognosis of BC patients based on the Kaplan-Meier-plotter. GSEA reviewed that these hub genes correlated with KEGG_CELL_CYCLE and HALLMARK_P53_PATHWAY. In conclusion, this study identified 11 key genes as BC potential prognosis biomarkers on the basis of integrated bioinformatics analysis. This finding will improve our knowledge of the BC progress and mechanisms.

Tim-3 promotes cell aggressiveness and paclitaxel resistance through NF-κB/STAT3 signalling pathway in breast cancer cells.

OBJECTIVE: Although T-cell immunoglobulin and mucin-domain containing molecule-3 (Tim-3) has been recognized as a promising target for cancer immunotherapy, its exact role in breast cancer has not been fully elucidated. METHODS: Tim-3 gene expression in breast cancer and its prognostic significance were analyzed. Associated mechanisms were then explored in vitro by establishing Tim-3-overexpressing breast cancer cells. RESULTS: In a pooled analysis of The Cancer Genome Atlas (TCGA) database, Tim-3 gene expression levels were significantly higher (P<0.001) in breast cancer tissue, compared with normal tissues. Tim-3 was a prognosis indicator in breast cancer patients [relapse-free survival (RFS), P=0.004; overall survival (OS), P=0.099]. Tim-3 overexpression in Tim-3low breast cancer cells promoted aggressiveness of breast cancer cells, as evidenced by enhanced proliferation, migration, invasion, tight junction deterioration and tumor-associated tubal formation. Tim-3 also enhanced cellular resistance to paclitaxel. Furthermore, Tim-3 exerted its function by activating the NF-κB/STAT3 signalling pathway and by regulating gene expression [cyclin D1 (CCND1), C-Myc, matrix metalloproteinase-1(MMP1), TWIST, vascular endothelial growth factor (VEGF) upregulation, concomitant with E-cadherin downregulation). Lastly, Tim-3 downregulated tight junction-associated molecules zona occludens (ZO)-2, ZO-1 and occludin, which may further facilitate tumor progression. CONCLUSIONS: Tim-3 plays an oncogenic role in breast cancer and may represent a potential target for antitumor therapy.

Fascia Suture Technique Is a Simple Approach to Reduce Postmastectomy Seroma Formation.

PURPOSE: Seroma formation is a common complication in breast cancer patients undergoing mastectomy, and it negatively affects patient recovery after surgery. The present study aimed to evaluate a simple method using fascia suture technique to fix the flap and reduce the incidence of seroma. METHODS: A single-center, prospective, randomized controlled trial was carried out among 160 patients who had undergone mastectomy from May 2018 to September 2019. All patients were randomly divided into the fascia suture group (n = 80) or control group (n = 80) and were followed up for at least 3 months for the assessment of immediate and late complications after surgery. RESULTS: No significant differences were observed between the 2 groups with regard to the basic characteristics. Duration of surgery in the fascia suture group was longer by about 6 minutes compared with that in the control group (114.93 ± 13.67 minutes vs. 108.81 ± 15.20 minutes, p = 0.008). The fascia suture group had a shorter duration of drain placement (10.99 ± 3.26 days vs. 13.85 ± 5.37 days, p < 0.001), a smaller volume of the total drainage (460.95 ± 242.92 mL vs. 574.83 ± 285.23 mL, p = 0.007), and the first 3-day drainage (224.96 ± 101.01 mL vs. 272.3 ± 115.47 mL, p = 0.006), compared with the control group. The incidence of seroma formation (G2 or G3) was significantly lower in the fascia suture group compared with the control group (28.8% vs. 12.5%, p = 0.033). Besides, there was no statistical difference between the 2 groups in the assessment of other complications, including postoperative pain, hematoma, surgical site infections, flap necrosis, and skin dimpling (all p > 0.050). CONCLUSION: The fascia suture technique is a simple and effective method for reducing seroma formation and should be used to prevent seroma formation after mastectomy. TRIAL REGISTRATION: Chinese Clinical Trials Registry Identifier: ChiCTR1800015913.

Tim-3 promotes tube formation and decreases tight junction formation in vascular endothelial cells.

As a negative immune checkpoint molecule, T-cell immunoglobulin domain and mucin domain containing molecule-3 (Tim-3) has been found to serve a crucial role in immune escape and tumour progression. Previous studies have reported that Tim-3 is important to endothelial cells and it has also been demonstrated to be involved in numerous types of human diseases, including melanoma, lymphoma, rickettsial infection and atherosclerosis; however, its exact mechanism of action remains largely unknown. In the present study, Tim-3 was overexpressed in vascular endothelial human lung microvascular endothelial cells (HMVECs) and human umbilical vein endothelial cells (HUVECs), and in vitro assays were used to determine that Tim-3 promoted cell proliferation, migration, invasion and tube formation through activating cyclin D1 (CCND1), Ras homolog gene family member A and vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2). Additionally, Tim-3 decreased tight junction (TJ) formation and the transepithelial resistance (TER) of endothelial cells by decreasing the expression levels of TJ protein 2, Occludin and claudin 1 (CLND1). In conclusion, these findings suggested that Tim-3 may exert a positive role in angiogenesis and a negative role in TJ formation in vascular endothelial cells, which may provide novel strategies for the treatment of Tim-3-associated diseases.

Calcium-Binding Protein S100P Promotes Tumor Progression but Enhances Chemosensitivity in Breast Cancer.

BACKGROUND: Chemoresistance remains one of the obstacles to overcome in the treatment of breast cancer. S100 calcium-binding protein P (S100P) has been observed to be overexpressed in several cancers and has been associated with drug resistance, metastasis, and prognosis. However, the role of S100P in chemoresistance in breast cancer has not been thoroughly determined. METHODS: Immunohistochemistry was used to evaluate the expression level of S100P protein in 22 pairs (pre-chemo and post-chemo) of breast cancer tissue from patients who underwent neoadjuvant chemotherapy. The influence of S100P on the biological behavior and chemosensitivity of breast cancer cells was then investigated. RESULTS: The protein level of S100P in breast cancer tissue was significantly higher than in benign fibroadenoma (p < 0.001). The S100P expression level was shown to be decreased by 46.55% after neoadjuvant chemotherapy (p = 0.015). Subgroup analysis revealed that S100P reduction (57.58%) was mainly observed in the HER2+ tumors (p = 0.027). Our in vitro experiments showed that the knockdown of S100P suppressed the proliferation, adhesion, migrative and invasive abilities of T47D and SK-BR-3 breast cancer cells. We further demonstrated that this knockdown increased the chemoresistance to paclitaxel and cisplatin in SK-BR-3 cells. We found S100P exerted its function by upregulating NF-κB, CCND1 and Vimentin, but downregulating E-cadherin. CONCLUSION: S100P promotes the aggressive properties of breast cancer cells and may be considered as a promising therapeutic target. Moreover, S100P can be used to predict the therapeutic effect of chemotherapy in HER2+ breast cancer patients.

Imaging Predictors for Nonsentinel Lymph Node Metastases in Breast Cancer Patients.

BACKGROUND: The relationship between imaging features and nonsentinel lymph node (NSLN) metastasis is not clear. OBJECTIVES: To determine whether imaging features could predict NSLN metastasis in sentinel lymph node (SLN)-positive breast cancer patients and to provide new clues for avoiding unnecessary axillary lymph node dissection. METHOD: 171 patients with clinically negative axillary lymph nodes and a pathologically positive SLN were recruited between January 2007 and January 2014. According to the Breast Imaging Reporting and Data System (BI-RADS), the effects of clinicopathological factors, especially imaging features, on NSLN metastases were assessed by univariate and multivariate statistical analyses. RESULTS: The average number of dissected SLNs was 2.11 (range, 1-6); 56 of the 171 (32.75%) patients exhibited NSLN metastases. In univariate analysis, tumor size, number of positive SLNs, ratio of positive SLNs, mammographic mass margins, ultrasonographic mass margins, and ultrasonographic vascularity were significantly correlated with NSLN involvement. Furthermore, through multivariate analysis, tumor size, number of positive SLNs, mammographic mass margins, and ultrasonographic vascularity were still independent predictors of NSLN involvement. Additionally, in SLN-positive patients, number of positive SLNs and ultrasonographic vascularity could also predict the tumor burden in NSLN. CONCLUSIONS: In addition to tumor size and the number of positive SLNs, mammographic mass margins and ultrasonographic vascularity were also independent predictors of NSLN metastases in SLN-positive patients of breast cancer. The number of positive SLNs and ultrasonographic vascularity could also predict the tumor burden in NSLN.

Efficacy of neoadjuvant chemotherapy and Annexin A3 expression in breast cancer.

PURPOSE: To observe the efficacy of neoadjuvant chemotherapy (NAC) in patients with breast cancer (BC) and to investigate the effect of Annexin A3 (ANXA3) expression. METHODS: 158 patients with BC treated in Yantai Yuhuangding Hospital from September 2015 to December 2017 were retrospectively analyzed. Among them, 83 cases were treated with epirubicin + cyclophosphamide + 5-fluorouracil (CEF group), 75 cases with epirubicin + cyclophosphamide + docetaxel (TEC group), with 3 cycles of chemotherapy. The efficacy and adverse reactions of the two NAC regimens were compared and analyzed. Tissue specimens were collected before and 10 days after the administration of chemotherapy in order to detect the expression of ANXA3 by qRT-PCR in each group. RESULTS: There were significant differences in the rates of complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD) between the two groups (z=10.716, p=0.013). The clinical effectiveness rate in the TEC group was significantly higher than that in the CEF group (p<0.05). There was no difference in the pathology grade between the two groups (p>0.05); however, the pathological effective rate in the TEC group was significantly higher than that in the CEF group (p<0.05). There was no difference in the rate of bone marrow suppression between the two groups (p>0.05). While there was no difference in the relative expression of ANXA3 between the two groups before chemotherapy, the relative expression of ANXA3 in the TEC group was lower than that in the CEF group after NAC (p<0.05). The relative expression in both groups after chemotherapy was lower than that before NAC (P<0.05). CONCLUSION: Compared with CEF regimen, NAC with TEC regimen can improve the clinical and pathological effectiveness rate, inhibit the expression of ANXA3, and improve the prognosis of patients, thus having a certain application prospect in NAC.

Analysis of the clinicopathological features and prognostic factors in 734 cases of Chinese Hui and Han patients with adenocarcinoma of the esophagogastric junction.

OBJECTIVE: To explore the clinicopathological features and prognostic factors of 734 cases of Chinese Hui and Han patients with adenocarcinoma of the esophagogastric junction (AEG). METHODS: In total, 734 patients were confirmed to have AEG by gastroscopy and pathology at the General Hospital of Ningxia Medical University between January 2002 and December 2012. Univariate and multivariate analyses of demographic, clinicopathological, and prognostic data were performed. RESULTS: In total, 734 AEG patients underwent surgical intervention, including 169 Hui patients and 565 Han patients. The male to female ratio was 9.5:1 in Hui patients and 6.4:1 in Han patients, and the average age in both groups was approximately 61 years. The Han patients were more likely to have a cigarette smoking history and an alcohol consumption history than the Hui patients (58.8% vs. 29.4%, p = 0.000; 45.8% vs. 14.6%, p = 0.000). The 5-year survival rate in the Hui and Han patients was 54.3% and 39.9%, respectively (p = 0.024). Age (p = 0.005), sex (p = 0.015), pathologic T stage (p = 0.056), pathologic N stage (p = 0.000), pathologic M stage (p = 0.001), number of resected lymph nodes (p = 0.001) and adjuvant chemoradiotherapy (p = 0.002) were significant independent prognostic factors. CONCLUSION: The AEG patients were primarily male and elderly in both Hui and Han groups with the prognosis of Hui patients better than Han patients. Age, sex, pathologic T3-4 stage, pathologic N stage, pathologic M stage, number of resected lymph nodes, and adjuvant chemoradiotherapy were significant independent factors predictive of the prognosis of AEG in both groups.