Assessing Diagnostic Performance Using the Transverse Plane Plus Coronal Plane Compared With the Transverse Plane Alone in Screening Automated Breast Ultrasound.

OBJECTIVES: The coronal plane is the unique display mode of automated breast (AB) ultrasound (US), which has valuable features of showing the entire breast anatomy and providing additional diagnostic value for breast lesions. However, whether adding the coronal plane could improve the diagnostic performance in screening breast cancer remains uncertain. This study aimed to evaluate the value of adding the coronal plane in interpretation for AB US screening. METHODS: In this retrospective study, AB US images from 644 women (396 in the no-finding group, 143 with benign lesions, and 105 with malignant lesions) aged 40-70 years were collected between January 2016 and October 2020. Four novice radiologists (with 1-5 years of experience with breast US) and four experienced radiologists (with >5 years of experience with breast US) were assigned to read all AB US images in the transverse plane plus coronal plane (T + C planes) and transverse plane (T plane) alone in separate reading sessions. Diagnostic performance, lesion conspicuity, and reading time were compared using analysis of variance. RESULTS: The mean reading time of all radiologists was significantly shorter in the T + C planes reading mode than in the T plane alone (115 ± 32 vs 128 ± 31 s, respectively; P < .05), and cancers had a higher conspicuity (odds ratio, 1.76; 95% confidence interval [CI], 1.00-3.08; P = .04). No significant differences were noted in the two reading modes (T + C planes vs T plane) in the sensitivity (82% [95% CI, 74-89%] vs 81% [95% CI, 74-88%], respectively; P = .68) and specificity (68% [95% CI, 62-75%] vs 70% [95% CI, 64-75%], respectively; P = .39) when Breast Imaging-Reporting and Data System (BI-RADS) 3 was set as the threshold. There were also no significant differences in the two reading modes (T + C planes vs T plane) in the sensitivity (70% [95% CI, 64-76%] vs 69% [95% CI, 63-75%], respectively; P = .39) and specificity (91% [95% CI, 87-96%] vs 91% [95% CI, 88-95%], respectively; P = .90) when BI-RADS 4 was set as the threshold. In addition, the mean areas under the receiver operating characteristic curves of all radiologists in the two reading modes (T + C planes vs T plane) were not significantly different (0.84 [95% CI, 0.79-0.89] vs 0.83 [95% CI, 0.78-0.89], respectively; P = .61). CONCLUSIONS: Adding a coronal plane in the AB US screening setting saved the reading time and improved the conspicuity of breast cancers but not the diagnostic performance.

Retraction Note to: MicroRNA-330-3p promotes cell invasion and metastasis in non-small cell lung cancer through GRIA3 by activating MAPK/ERK signaling pathway.

An amendment to this paper has been published and can be accessed via the original article.

18F-FDG PET/CT SUVmax and serum CEA levels as predictors for EGFR mutation state in Chinese patients with non-small cell lung cancer.

The epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) contribute to an increased response rate, compared with chemotherapy, in patients with inhibitor-sensitive EGFR mutations. The present study evaluated the association between the maximum standardized uptake value (SUVmax) of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT), as well as serum carcinoembryonic antigen (CEA) levels and EGFR mutations prior to treatment, in patients with non-small cell lung cancer (NSCLC). Patients with histologically confirmed NSCLC (n=167), who underwent an 18F-FDG PET/CT scan, EGFR mutation analysis and a serum CEA test participated in the present study. Multivariate logistic regression analysis was used to analyze predictors of EGFR mutations. Receiver-operating characteristic (ROC) curve analysis was performed to determine the efficient cut-off value. Survival rate analysis was evaluated according to SUVmax and EGFR mutation status. A decreased SUVmax and an increased CEA level was observed in patients with EGFR-mutations, compared with patients with wild-type primary lesions and metastatic lymph nodes. The exon 19 EGFR mutation was associated with increased SUVmax, compared with the exon 21 L858R mutation. The ROC analysis indicated that an 18F-FDG PET/CT uptake SUVmax >11.5 may be a predictor of the wild-type EGFR genotype and increased CEA levels (CEA >9.4 ng/ml) were associated with EGFR mutations. Furthermore, patients with no smoking history, low SUVmax of the primary tumor, metastatic lymph nodes and a high CEA level were significantly associated with EGFR mutation status. The results of the present study indicated that patients with advanced NSCLC, particularly Chinese patients, with decreased SUVmax and increased CEA levels are associated with EGFR mutations, which may serve as predictors for the EGFR-TKI therapeutic response.

Erratum: A germline alteration of ERBB2 increases the risk of breast cancer in Chinese Han women with a familial history of malignant tumors.

[This corrects the article DOI: 10.3892/ol.2019.10646.].

MicroRNA-330-3p promotes brain metastasis and epithelial-mesenchymal transition via GRIA3 in non-small cell lung cancer.

Brain metastasis (BM) is associated with poor prognosis in patients with non-small cell lung cancer (NSCLC). We sought to identify microRNAs (miRNAs) that could serve as biomarkers to differentiate NSCLC patients with and without BM. Logistic regression was conducted with 122 NSCLC patients (60 without BM, 62 with BM) to assess the association between miRNAs and BM. We confirmed several risk factors for BM and revealed that serum miR-330-3p levels are higher in NSCLC patients with BM than that without BM. Overexpression of miR-330-3p promoted proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of NSCLC cells in vitro and NSCLC tumorigenesis in vivo. Knocking down miR-330-3p suppressed this metastatic phenotype. We identified putative miR-330-3p target genes by comparing mRNA microarray analysis data from A549 cells after miR-330-3p knockdown with candidate miR-330-3p target genes predicted by public bioinformatic tools and luciferase reporter assays. We found that GRIA3 is a target of miR-330-3p and that miR-330-3p stimulates EMT progress by mediating GRIA3-TGF-ß1 interaction. Our results provide novel insight into the role of miR-330-3p in NSCLC metastasis, and suggest miR-330-3p may be a useful biomarker for identifying NSCLC with metastatic potential.

A germline alteration of ERBB2 increases the risk of breast cancer in Chinese Han women with a familial history of malignant tumors.

Previous studies have demonstrated that a family history of breast cancer is considered a risk factor, and hereditary factors may be involved in breast cancer pathogenesis. Next-generation sequencing techniques were used to analyze 111 cancer-associated genes in patients with breast cancer with a familial history of malignant tumors in the pre-experiment and a novel variant, receptor tyrosine-protein kinase erbB-2 (ERBB2) c.338G>A: p.R113Q was identified in two cases of breast cancer. ERBB2 is considered an important oncogene, and overexpression or mutation of the ERBB2 gene may lead to the occurrence or metastasis of tumors. To assess a potential association between rs185670819 and breast cancer, 117 patients with breast cancer and a familial history of any cancer, who were diagnosed by experienced pathologists at the Xijing Hospital (Shaanxi, China) between July 2015 and December 2016, were recruited. The presence of the missense variant was confirmed using bi-directional Sanger sequencing of samples from the patients with breast cancer and 250 healthy controls. The effects of the missense mutation on the structure and function of ERBB2 were analyzed in silico. The missense variant, R113Q, in patients with breast cancer with a familial history of malignant tumors in China, was present in 8 patients [6.8% (95% CI: 3.21-13.45)] and 3 of 250 healthy controls [1.2% (95% CI: 0.31-3.76; OR=6.04, 95% CI: 1.573-23.214, P=0.009)]. Of the 8 patients with the R113Q variant, 6 patients had a family history of cancer of the digestive system. The present study suggests that ERBB2 c.338G>A: p.R113Q may be a potential risk factor in the development and progression of breast cancer.

Performance and Reading Time of Automated Breast US with or without Computer-aided Detection.

BackgroundComputer-aided detection (CAD) systems may be used to help radiologists interpret automated breast (AB) US images. However, the optimal use of CAD with AB US has, to the knowledge of the authors, not been determined.PurposeTo compare the performance and reading time of different readers by using AB US CAD system to detect breast cancer in different reading modes.Materials and MethodsIn this retrospective study, 1485 AB US images (282 with malignant lesions, 695 with benign lesions, and 508 healthy) in 1452 women (mean age, 43.7 years; age range, 19-82 years) including 529 (36.4%) women who were asymptomatic were collected between 2016 and 2017. A CAD system was used to interpret the images. Three novice readers with 1-3 years of US experience and three experienced readers with 5-10 years of US experience were assigned to read AB US images without CAD, at a second reading (after the reader completed a full unaided interpretation), and at concurrent reading (use of CAD at the start of the assessment). Diagnostic performances and reading times were compared by using analysis of variance.ResultsFor all readers, the mean area under the receiver operating characteristic curve improved from 0.88 (95% confidence interval [CI]: 0.85, 0.91) at without-CAD mode to 0.91 (95% CI: 0.89, 0.92; P < .001) at the second-reading mode and 0.90 (95% CI: 0.89, 0.92; P = .002) at the concurrent-reading mode. The mean sensitivity of novice readers in women who were asymptomatic improved from 67% (95% CI: 63%, 74%) at without-CAD mode to 88% (95% CI: 84%, 89%) at both the second-reading mode and the concurrent-reading mode (P = .003). Compared with the without-CAD and second-reading modes, the mean reading time per volume of concurrent reading was 16 seconds (95% CI: 11, 22; P < .001) and 27 seconds (95% CI: 21, 32; P < .001) shorter, respectively.ConclusionComputer-aided detection (CAD) was helpful for novice readers to improve cancer detection at automated breast US in women who were asymptomatic. CAD was more efficient when used concurrently for all readers.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by Slanetz in this issue.

Correction to: MicroRNA-330-3p promotes cell invasion and metastasis in non-small cell lung cancer through GRIA3 by activating MAPK/ERK signaling pathway.

The original article [1] contained incorrect affiliations for the authors.

MicroRNA-330-3p promotes cell invasion and metastasis in non-small cell lung cancer through GRIA3 by activating MAPK/ERK signaling pathway.

BACKGROUND: Brain metastasis (BM) is associated with poor prognosis in patients with non-small cell lung cancer (NSCLC). Recent studies demonstrated that microRNA-330-3p (miR-330-3p) was involved in NSCLC brain metastasis (BM). However, the exact parts played by miR-330-3p in BM of NSCLC remain unknown. Discovery and development of biomarkers and elucidation of the mechanism underlying BM in NSCLC is critical for effective prophylactic interventions. Here, we evaluated the expression and biological effects of miR-330-3p in NSCLC cells and explored the underlying mechanism of miR-330-3p in promoting cell migration and invasion in NSCLC. METHODS: Stable over-expression and knockdown of miR-330-3p in NSCLC cells was constructed with lentivirus. Expression levels of miR-330-3p in NSCLC cells were quantified by quantitive real-time PCR (qRT-PCR). The effects of miR-330-3p on NSCLC cells were investigated using assays of cell viability, migration, invasion, cell cycle, apoptosis, western blotting, immunohistochemical, and immunofluorescence staining. A xenograft nude mouse model and in situ brain metastasis model were used to observe tumor growth and brain metastasis. The potential target of miR-330-3p in NSCLC cells was explored using the luciferase reporter assay, qRT-PCR, and western blotting. The miR-330-3p targets were identified using bioinformatics analysis and verified by luciferase reporter assay. The correlation between GRIA3 and DNA methyltransferase (DNMT) 1 and DNMT3A was tested by RT-PCR, western blotting, and co-immunoprecipitation (IP). RESULTS: miR-330-3p was significantly up-regulated in NSCLC cell lines. MTT assay, transwell migration, and invasion assays showed that miR-330-3p promoted the growth, migration, and invasion of NSCLC cells in vitro and induced tumor growth and metastasis in vivo. Luciferase reporter assays showed that GRIA3 was a target of miR-330-3p. qRT-PCR and western blotting exhibited that miR-330-3p promoted the growth, invasion, and migration of NSCLC cells by activating mitogen-activated protein kinase (MAPK)/extracellular-regulated protein kinases (ERK) signaling pathway. Furthermore, miR-330-3p up-regulated the total DNA methylation in NSCLC cells, and co-IP-demonstrated GRIA3 was directly related with DNMT1 and DNMT3A. CONCLUSIONS: miR-330-3p promoted the progression of NSCLC and might be a potential target for the further research of NSCLC brain metastasis.

Clinical features and prognostic factors of small cell lung cancer: A retrospective study in 148 patients.

To better understand the outcomes of small cell lung cancer (SCLC), we examined the clinical features and prognostic factors of SCLC in this study. A total of 148 patients who were diagnosed as having SCLC between January 2009 and December 2013 in Cancer Center of Union Hospital, Wuhan, China, were enrolled and their clinical features and prognostic factors were retrospectively analyzed. Log-rank test and Cox regression model were employed for analysis of prognostic factors. The 1- and 2-year overall survival (OS) rates were 59.7% and 25.7%, respectively, for limited disease (LD) patients whose median survival time (MST) was 16 months. The 1- and 2-year OS rates were 29.5% and 5.3%, respectively, for extensive disease (ED) patients whose MST was 10 months. The univariate analysis and multivariate analysis revealed that age, tumor stage, serum CEA and Ki-67 antigen were significantly correlated to the outcomes of SCLC, and they were significant prognostic factors for SCLC.

PIDD Mediates Radiation-Induced Microglia Activation.

Radiation-induced brain injury (RIBI) is the most common adverse effect that occurs after cranial radiation therapy (CRT). We have previously reported that CRT-induced release of pro-inflammatory cytokines in brain tissues and inhibition of neurogenesis in the hippocampus might be caused by microglial activation and may play an important role in RIBI. In this study we examined the role of p53-induced protein with a death domain (PIDD) in radiation-induced activation of BV-2 cells. BV-2 cells were transfected with antisense oligonucleotide control mRNA or antisense oligonucleotide-targeted PIDD mRNA and were sham or 16 Gy irradiated. The state of microglia and expression of pro-inflammatory cytokines were detected using real-time polymerase chain reaction, Western blotting, immunofluorescence and flow cytometry. Findings from this study suggest that silencing PIDD expression could inhibit microglial activation by downregulating the PIDD-C/NF-κß transcription pathway. PIDD acts as a critical switcher between the NF-κß transcription pathway and radiation-induced apoptosis. Given these findings, this study offers a potential novel approach to further combination treatment of RIBI.

Corilagin Attenuates Radiation-Induced Brain Injury in Mice.

Cranial irradiation-induced inflammation plays a critical role in the initiation and progression of radiation-induced brain injury (RIBI). Anti-inflammation treatment may provide therapeutic benefits. Corilagin (beta-1-O-galloyl-3, 6-(R)-hexahydroxydiphenoyl-D-glucose, C27H22O18) was a novel member of the tannin family with anti-inflammatory properties and is isolated from some medicinal plants, such as Phyllanthus amarus and Caesalpinia coriaria. In this study, the effect of Corilagin on RIBI was investigated and the underlying mechanisms were explored. Spatial learning and memory ability of mice were investigated by the Morris water maze test. Evans blue leakage and electron microscopy were used to assess the integrity of blood-brain barrier (BBB). The mRNA and protein expressions of inflammatory cytokines, TNF-α and IL-1ß, were measured by using real-time PCR and Western blotting. The activation of microglial cells and expression of TNF-α were examined by immunofluorescence staining. Phosphorylated signal transducers and activators of transcription 3 (p-STAT3) and IκBα, and the translocation of p65 from cytoplasm to nucleus were detected by using Western blotting. Morris water maze test showed that Corilagin ameliorated the neurocognitive deficits in RIBI mice. Evans blue leakage and electron microscopy exhibited that Corilagin partially protected the BBB integrity from cranial irradiation-caused damage; immunofluorescence staining showed that Corilagin could inhibit microglial activation and TNF-α expression. Real-time PCR and Western blotting revealed that Corilagin downregulated the expression of TNF-α and IL-1ß and inhibited the irradiation-induced activation of NF-κB pathways by upregulating p-STAT3 expression. In conclusion, Corilagin could attenuate RIBI through inhibiting microglial activation and the expressions of inflammatory cytokines. Corilagin might inhibit the activation of NF-κB pathway in a STAT3-associated manner, thereby downregulating the inflammatory cytokine expressions.