Ultrasound-assisted biomimetic nanobubbles for targeted treatment of atherosclerosis.

Cardiovascular disease caused by atherosclerosis remains the main reason of death in the worldwide scale. Although oxidative stress plays a key role in the initiation and progression of atherosclerosis, current antioxidant drugs have limited efficacy. To resolve this problem, we constructed Nox2 siRNA-loaded nanobubbles (PNBs-siNox2) coated with platelet membranes to utilize their antioxidant stress activity and targeting effect for atherosclerosis treatment. After platelet membranes modification, the capacity of PNBs-siNox2 to target collagen, foam cells, or human umbilical vein endothelial cells (HUVECs) was significantly increased. Moreover, our study demonstrated that under ultrasonic irradiation, biomimetic nanobubbles were more effective at targeting atherosclerotic plaques and delivering genes into cells. In the present study, we provided a biomimetic gene loading strategy based on nanoplatform for noninvasive, precise and efficient therapy of atherosclerosis, which further improved the efficiency of gene transfection and effectively slowed the progression of atherosclerotic plaques when combined with ultrasound.

Signal peptidase 21 suppresses cell proliferation, migration, and invasion via the PTEN-PI3K/Akt signaling pathway in lung adenocarcinoma.

Background: In a previous study, a total of 568 differentially expressed proteins including the signal peptidase SPC21 were identified from lung adenocarcinoma (LUAD) and paired normal lung tissues. In this study, the role of SPC21 in LUAD progression was investigated. Methods: The relationships and protein-protein interaction network of proteins differentially expressed between paired LUAD samples and adjacent normal tissues samples were identified via the String and Pajek software, respectively. The expression levels of the hub protein SPC21 were analyzed in 84 LUAD-normal paired tissues via immunohistochemistry. The prognostic value of SPC21 mRNA was investigated in 478 LUAD patients from TCGA and GTEx datasets. siRNAs were used in A549 and NCI-H1299 cells to knockdown SPC21. The SPC21 biological function was evaluated using the CCK-8, EdU, plate colony formation, transwell, wound healing, and adhesion assays. Results: Patients with lower SPC21 mRNA levels tended to have worse prognosis (overall survival) than those with higher mRNA levels. SPC21 expression was significantly downregulated in LUAD tumor tissues compared with that in paired normal tissues (P < 0.001). Functionally, SPC21 knockdown promoted cell growth, migration, and invasion. Further analyses showed that SPC21 inactivated Akt signaling, and the Akt inhibitor MK-2206 blocked the tumor-promoting effects of SPC21 knockdown. Conclusions: SPC21 plays a tumor suppressor role in LUAD cells by targeting the PTEN-PI3K/Akt axis and might be used as a prognostic indicator and therapeutic target in LUAD patients.

Essential role for STAT3/FOXM1/ATG7 signaling-dependent autophagy in resistance to Icotinib.

BACKGROUND: The contribution of autophagy to cancer therapy resistance remains complex, mainly owing to the discrepancy of autophagy mechanisms in different therapy. However, the potential mechanisms of autophagy-mediated resistance to icotinib have yet to be elucidated. METHODS: The effect of autophagy in icotinib resistance was examined using a series of in vitro and in vivo assays. The results above were further verified in biopsy specimens of lung cancer patients before and after icotinib or gefitinib treatment. RESULTS: Icotinib increased ATG3, ATG5, and ATG7 expression, but without affecting Beclin-1, VPS34 and ATBG14 levels in icotinib-resistant lung cancer cells. Autophagy blockade by 3-MA or silencing Beclin-1 had no effects on resistance to icotinib. CQ effectively restored lung cancer cell sensitivity to icotinib in vitro and in vivo. Notably, aberrantly activated STAT3 and highly expressed FOXM1 were required for autophagy induced by icotinib, without the involvement of AMPK/mTOR pathway in this process. Alterations of STAT3 activity using genetic and/or pharmacological methods effectively affected FOXM1 and ATG7 levels increased by icotinib, with altering autophagy and icotinib-mediated apoptosis in resistant cells. Furthermore, silencing FOXM1 impaired up-regulated ATG7 induced by STAT3-CA and icotinib. STAT3/FOXM1 signalling blockade also reversed resistance to icotinib in vivo. Finally, we found a negative correlation between STAT3/FOXM1/ATG7 signalling activity and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) treatment efficacy in patients undergoing EGFR-TKIs treatment. CONCLUSIONS: Our findings support that STAT3/FOXM1/ATG7 signalling-induced autophagy is a novel mechanism of resistance to icotinib, and provide insights into potential clinical values of ATG7-dependent autophagy in icotinib treatment.

DDX47 promotes cell proliferation and migration in lung adenocarcinoma.

This study aimed to investigate the role of DEAD-box helicase 47 (DDX47) in lung adenocarcinoma (LUAD). Our results demonstrated that DDX47 was highly expressed in LUAD tissues, and its high expression predicted a poor prognosis. Bioinformatics analysis indicated that DDX47 involved RNA processing and cell division. Furthermore, knockdown of DDX47 reduced cell proliferation and migration in vitro. In sum, our data confirmed the cancer-promoting effect of DDX47.

Pretreatment HDL-C and ApoA1 are predictive biomarkers of progression-free survival in patients with EGFR mutated advanced non-small cell lung cancer treated with TKI.

BACKGROUND: We aimed to explore the correlation between blood lipids (high density lipoprotein cholesterol [HDL-C] and apolipoprotein A1 [ApoA1]) and epidermal growth factor receptor (EGFR) T790M mutation, as well as its predictive role in clinical efficacy and progression-free survial (PFS) in advanced non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (EGFR-TKI). METHODS: We retrospectively collected information of 153 patients with advanced NSCLC harboring exon EGFR mutation and receiving EGFR-TKI. RESULTS: The best cutoff value for HDL-C and ApoA1 was determined to be 1.15 and 1.14 mmol/l. The overall response rate (ORR) was 67.7% in the high HDL-C group and 46.6% in the low HDL-C group, respectively. The ORR of the high ApoA1 group showed a significant increase than that of the low ApoA1 group (68.1% vs. 38.5%). The mean ApoA1 level of the EGFR T790M mutation-positive group was significantly higher than that of the EGFR T790M mutation-negative group (1.13 g/l vs. 1.01 g/l). Patients with high ApoA1 levels were related to the EGFR T790M mutation (r = 0.324). (3) The median progression-free survival (PFS) of the high HDL-C group and low HDL-C group were 13.00 months and 10.20 months. The median PFS of the high ApoA1 group and the low ApoA1 group were 12.10 and 10.00 months, respectively. Multivariate Cox stepwise regression model analysis demonstrated ECOG PS, pathological type and HDL-C were confirmed as critical and independent predictors of PFS. CONCLUSIONS: Patients with EGFR T790M mutations often show higher ApoA1 levels. Peripheral serum HDL-C and ApoA1 before treatment can be used as potential significant factors for predicting clinical efficacy and PFS in advanced NSCLC patients treated with EGFR-TKI.

Quantitative assessment of right ventricular size and function with multiple parameters from artificial intelligence-based three-dimensional echocardiography: A comparative study with cardiac magnetic resonance.

AIMS: This study aimed to explore the validation and the diagnostic value of multiple right ventricle (RV) volumes and functional parameters derived from a novel artificial intelligence (AI)-based three-dimensional echocardiography (3DE) algorithm compared to cardiac magnetic resonance (CMR). METHODS AND RESULTS: A total of 51 patients with a broad spectrum of clinical diagnoses were finally included in this study. AI-based RV 3DE was performed in a single-beat HeartModel mode within 24 hours after CMR. In the entire population, RV volumes and right ventricular ejection fraction (RVEF) measured by AI-based 3DE showed statistically significant correlations with the corresponding CMR analysis (p < 0.05 for all). However, the Bland-Altman plots indicated that these parameters were slightly underestimated by AI-based 3DE. Based on CMR derived RVEF < 45% as RV dysfunction, end-systolic volume (ESV), end-systolic volume index (ESVi), stroke volume (SV), and RVEF showed great diagnostic performance in identifying RV dysfunction, as well as some non-volumetric parameters, including tricuspid annular systolic excursion (TAPSE), fractional area change (FAC), and free-wall longitudinal strains (LS) (p < 0.05 for all). The cutoff value was 43% for RVEF with a sensitivity of 94% and specificity of 67%. CONCLUSION: AI-based 3DE could provide rapid and accurate quantitation of the RV volumes and function with multiple parameters. Both volumetric and non-volumetric measurements derived from AI-based 3DE contributed to the identification of the RV dysfunction.

Normalized Cardiac Structure and Function in COVID-19 Survivors Late After Recovery.

Background: Coronavirus disease 2019 can result in myocardial injury in the acute phase. However, information on the late cardiac consequences of coronavirus disease 2019 (COVID-19) is limited. Methods: We conducted a prospective observational cohort study to investigate the late cardiac consequences of COVID-19. Standard echocardiography and myocardial strain assessment were performed, and cardiac blood biomarkers were tested in 86 COVID-19 survivors 327 days (IQR 318-337 days) after recovery. Comparisons were made with 28 age-matched and sex-matched healthy controls and 30 risk factor-matched patients. Results: There were no significant differences in all echocardiographic structural and functional parameters, including left ventricular (LV) global longitudinal strain, right ventricular (RV) longitudinal strain, LV end-diastolic volume, RV dimension, and the ratio of peak early velocity in mitral inflow to peak early diastolic velocity in the septal mitral annulus (E/e') among COVID-19 survivors, healthy controls and risk factor-matched controls. Even 26 patients with myocardial injury at admission did not have any echocardiographic structural and functional abnormalities. There were no significant differences among the three groups with respect to serum concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (cTnI). Conclusion: This study showed that COVID-19 survivors, including those with myocardial injury at admission and those with severe and critical types of illness, do not have any echocardiographic evidence of cardiac structural and functional abnormalities 327 days after diagnosis.

Non-invasive Global and Regional Myocardial Work Predicts High-Risk Stable Coronary Artery Disease Patients With Normal Segmental Wall Motion and Left Ventricular Function.

Background: Previous studies suggested that myocardial work (MW) may identify abnormalities in the left ventricular (LV) function and establish a more sensitive index for LV dysfunction at the early stage. This study aimed to explore the value of global and regional MW parameters in predicting high-risk stable coronary artery disease (SCAD) patients with normal wall motion and preserved LV function. Patients and Methods: A total of 131 patients, who were clinically diagnosed as SCAD with normal wall motion and LV function, were finally included in this study. Global MW parameters, including global work index (GWI), global constructive work (GCW), global waste work (GWW), and global work efficiency (GWE) were measured with non-invasive LV pressure-strain loops constructed from speckle-tracking echocardiography. Regional myocardial work index (RWI) and work efficiency (RWE) were also calculated according to the perfusion territory of each major coronary artery. All patients underwent coronary angiography and were divided into the high-risk SCAD group, the non-high-risk SCAD group, and the No SCAD group according to the range and degrees of coronary arteries stenosis. Results: The global longitudinal strain (GLS), GWI and GCW were statistically different (P < 0.001) among the three groups. In the high-risk SCAD group, GLS, GWI, and GCW were significantly lower than the other two groups (P < 0.05). Receiver operating characteristic analysis demonstrated GWI and GCW could predict high-risk SCAD at a cutoff value of 1,808 mm Hg% (sensitivity, 52.6%; specificity, 87.8%; predictive positive value, 76.3%; predictive negative value, 69.9%) and 2,308 mm Hg% (sensitivity, 80.7%; specificity, 64.9%; predictive positive value, 63.3%; predictive negative value, 80.0%), respectively. Multivariate analyses showed that carotid plaque, decreased GWI, and GCW was independently related to high-risk SCAD. The cutoff values of RWILAD, RWILCX, and RWIRCA were 2,156, 1,929, and 1,983 mm Hg% in predicting high-risk SCAD, respectively (P < 0.001). When we combined RWI in two or three perfusion regions, the diagnostic performance of SCAD was improved (P < 0.001). Conclusions: Both global and regional MW parameters have great potential in non-invasively predicting high-risk SCAD patients with normal wall motion and preserved LV function, contributing to the early identification of high-risk patients who may benefit from revascularization therapy.

Contrast-enhanced ultrasound molecular imaging of activated platelets in the progression of atherosclerosis using microbubbles bearing the von Willebrand factor A1 domain.

Platelet-endothelial interactions have been linked to increased inflammatory activation and a prothrombotic state in atherosclerosis. The interaction between von Willebrand factor (vWF)-A1 domain and platelet glycoprotein (GP) Ib/IX plays a significant role in mediating the adhesion of platelets to the injured endothelium. In the present study, contrast-enhanced ultrasound (CEU) molecular imaging with microbubbles bearing the vWF-A1 domain was performed to non-invasively monitor activated platelets on the vascular endothelium in the procession of atherosclerosis. A targeted CEU contrast agent was prepared by attaching the vWF-A1 domain to the shell of microbubbles (MbA1). Rat isotype control antibody was used to produce control (Mbctrl) microbubbles. The binding of MbA1 and Mbctrl to activated platelets was assessed in in vitro flow chamber experiments. Apolipoprotein E (ApoE-/-) deficient mice were studied as a model of atherosclerosis. At 8, 16 and 32 weeks of age, CEU molecular imaging of the proximal aorta with MbA1 and Mbctrl was performed and the imaging signals from microbubbles were quantified. Atherosclerotic lesion severity and platelets on the endothelial surface were assessed by histology and immunohistochemistry. In in vitro flow chamber studies, attachment of MbA1 to activated platelets on culture dishes was significantly greater than that of Mbctrl across a range of shear stresses (P<0.05). The attachment of Mbctrl was sparse and not related to the aggregated platelets. As lesion development progressed in the ApoE-/- mice, molecular imaging of activated platelets demonstrated selective signal enhancement of MbA1 (P<0.05 vs. Mbctrl) at all ages. Selective signal enhancement from MbA1 increased from 8 to 32 weeks of age. Immunohistochemistry for GPIIb revealed the presence of platelets on the endothelial cell surface in each group of ApoE-/- mice and that the degree of platelet deposits was age-dependent. The results of the present study indicated that non-invasive CEU molecular imaging with targeted microbubbles bearing the vWF-A1 domain could not only detect activated platelets on the vascular endothelium but also indicate lesion severity in atherosclerosis.

Erratum: Long non-coding RNA LINC01116 is overexpressed in lung adenocarcinoma and promotes tumor proliferation and metastasis.

[This corrects the article on p. 4302 in vol. 12, PMID: 32913506.].

GALNT2 promotes cell proliferation, migration, and invasion by activating the Notch/Hes1-PTEN-PI3K/Akt signaling pathway in lung adenocarcinoma.

AIMS: Our study aimed to investigate the function of GALNT2 in lung adenocarcinoma (LUAD). MAIN METHODS: We used network tools and tissue microarray immunohistochemistry to measure the expression levels of GALNT2 in LUAD. Kaplan-Meier curves and Cox regression methods were used in survival analysis. We detected the role of GALNT2 in cell lines by Cell Counting Kit-8, colony formation, transwell, and wound healing assays. We performed Western blotting to evaluate downstream protein levels. KEY FINDINGS: GALNT2 was highly expressed in LUAD samples and indicated a poor prognosis. Knockdown of GALNT2 suppressed cell line proliferation, migration, and invasion abilities, while overexpression of GALNT2 enhanced those phenotypes. Moreover, GALNT2 activated Notch/Hes1-PTEN-PI3K/Akt signaling axis. SIGNIFICANCE: Our data confirmed the cancer-promoting effect of GALNT2, and might provide a new approach for LUAD therapy.

Impact of Patent Foramen Ovale Anatomic Features on Right-to-Left Shunt in Patients with Cryptogenic Stroke.

The purpose of this study was to investigate the impact of the morphologic characteristics of patent foramen ovale (PFO) on right-to-left shunt (RLS) in patients with PFO and cryptogenic stroke using transesophageal echocardiography and saline contrast transthoracic echocardiography (c-TTE). Of the 165 patients with PFO stroke, both the height and the length of PFO in the provoked RLS group were smaller than those in the constant RLS group. PFO height, interatrial septum mobility and proportion of atrial septal aneurysms were greater in the severe RLS group than in the mild and moderate RLS groups. Multivariate analysis revealed that PFO height and interatrial septum mobility were independent predictors of severe RLS. Multiple territorial ischemic lesions were more common in the severe RLS or constant RLS group. Our findings indicated that the severity of RLS was related to the anatomic features in PFO, inducing different cerebral ischemia lesion patterns in cryptogenic stroke patients with PFO.

ADFP promotes cell proliferation in lung adenocarcinoma via Akt phosphorylation.

Previously, we identified differentially expressed proteins, including ADFP, between lung adenocarcinoma (LAC) tissue and paired normal bronchioloalveolar epithelium. In this study, we investigated the role of ADFP in LAC. ADFP levels in the serum of patients with lung cancer and benign diseases were measured by enzyme-linked immunosorbent assays (ELISA). shRNA was used to knock-down or overexpress ADFP in A549 and NCI-H1299 cells. The biological function of ADFP and its underlying mechanisms was evaluated in vivo and in vitro. ADFP was highly expressed in the serum of lung cancer patients, especially those with LAC. ADFP promoted cell proliferation and up-regulated the p-Akt/Akt ratio in A549 and NCI-H1299 cells in vitro. Furthermore, in nude mice, ADFP promoted tumour formation with high levels of p-Akt/Akt, Ki67 and proliferating cell nuclear antigen (PCNA). Similar to the effect of ADFP knock-down, MK-2206 (a phosphorylation inhibitor of Akt) reduced A549 and NCI-H1299 cell proliferation. In ADFP-overexpressing A549 and NCI-H1299 cells, proliferation was suppressed by MK-2206 and returned to the control level. ADFP did not regulate invasion, migration or adhesion in LAC cells. Together, these results suggest that ADFP promotes LAC cell proliferation in vitro and in vivo by increasing Akt phosphorylation level.

Long non-coding RNA LINC01116 is overexpressed in lung adenocarcinoma and promotes tumor proliferation and metastasis.

Long non-coding RNA LINC01116 is involved in the occurrence and progression of a variety of cancers. However, the specific role of LINC01116 in lung adenocarcinoma (LUAD) remains unclear. In this work, we found that LINC01116 was overexpressed in LUAD tissues and cell lines and that increased expression was significantly associated with worse prognoses in patients with LUAD. Univariate and multivariate Cox regression analyses indicated that LINC01116 was an independent risk factor for the prognosis of patients with LUAD. Downregulation of LINC01116 significantly inhibited cell proliferation and migration, promoted cell apoptosis, and prevented cell progression from G1 to S phase. In addition, downregulation of LINC01116 significantly inhibited the epithelial-mesenchymal transition, leading to an increased expression of the epithelial marker E-cadherin and decreased expression of the mesenchymal markers N-cadherin and vimentin. In summary, our results suggest that LINC01116 may act as an oncogene in LUAD and may be a valuable prognostic biomarker for patients with LUAD.

Identification and validation of tumor microenvironment-related genes of prognostic value in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a major subtype of non-small cell lung cancer. Despite significant progress in its diagnosis and treatment, the mortality and morbidity rate of LUAD remains high worldwide. The aim of the present study was to perform a systematic investigation of the tumor microenvironment (TME) and identify TME-related genes of prognostic value in patients with LUAD. Firstly, the immune scores and stromal scores of patients with LUAD from The Cancer Genome Atlas were calculated using the Estimation of STromal and Immune cells in MAlignant Tumors using Expression data algorithm, and a total of 281 prognostic TME-related genes were identified. Subsequently, functional analysis and protein-protein interaction network analysis revealed that these genes were mainly related to immune response, inflammatory response and chemotaxis. Finally, two independent LUAD cohorts from the Gene Expression Omnibus database were used to validate these genes, and 4 genes (GTPase IMAP family member 1, T-cell surface glycoprotein CD1b, integrin alpha-L and leukocyte surface antigen CD53) were identified, and downregulation of these genes was indicated to be associated with poor overall survival rate in patients with LUAD. In conclusion, a comprehensive analysis of TME was performed and 4 prognostic TME-related genes in patients with LUAD were identified.

Upregulation of desmoglein 2 and its clinical value in lung adenocarcinoma: a comprehensive analysis by multiple bioinformatics methods.

BACKGROUND: Desmoglein-2 (DSG2), a desmosomal adhesion molecule, is found to be closely related to tumorigenesis in recent years. However, the clinical value of DSG2 in lung adenocarcinoma remains unclear. METHODS: Real-time reverse transcription-quantitative polymerase chain reaction (qRT-PCR) was utilized to detect the expression of DSG2 in 40 paired lung adenocarcinoma tissues and corresponding non-cancerous tissues. Data from The Cancer Genome Atlas (TCGA) and Oncomine datasets were also downloaded and analyzed. The correlation between DSG2 and clinicopathological features was investigated. The expression of DSG2 protein by immunohistochemical was also detected from tissue microarray and the Human Protein Atlas database. Integrated meta-analysis combining the three sources (qRT-PCR data, TCGA data and Oncomine datasets) was performed to evaluate the clinical value of DSG2. Univariate and multivariate Cox regression analyses were used to explore the prognostic value of DSG2. Then, co-expressed genes were calculated by Pearson correlation analysis. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to investigate the underlying molecular mechanism. The expression level in lung adenocarcinoma and prognostic significance of the top ten co-expressed genes were searched from Gene Expression Profiling Interactive Analysis (GEPIA) online database. RESULTS: DSG2 was highly expressed in lung adenocarcinoma tissues based on qRT-PCR, TCGA and Oncomine datasets. The protein expression of DSG2 was also higher in lung adenocarcinoma. According to qRT-PCR and TCGA, high DSG2 expression was positively associated with tumor size (p = 0.027, p = 0.001), lymph node metastasis (p = 0.014, p < 0.001) and TNM stage (p = 0.023, p < 0.001). The combined standard mean difference values of DSG2 expression based on the three sources were 1.30 (95% confidence interval (CI): 1.08-1.52) using random effect model. The sensitivity and specificity were 0.73 (95% CI [0.69-0.76]) and 0.96 (95% CI [0.89-0.98]). The area under the curve based on summarized receiver operating characteristic (SROC) curve was 0.79 (95% CI [0.75-0.82]). Survival analysis revealed that high DSG2 expression was associated with a short overall survival (hazard ratio [HR] = 1.638; 95% CI [1.214-2.209], p = 0.001) and poor progression-free survival (HR = 1.475; 95% CI [1.102-1.974], p < 0.001). A total of 215 co-expressed genes were identified. According to GO and KEGG analyses, these co-expressed genes may be involved in "cell division", "cytosol", "ATP binding" and "cell cycle". Based on GEPIA database, seven of the top ten co-expressed genes were highly expressed in lung adenocarcinoma (DSC2, SLC2A1, ARNTL2, ERO1L, ECT2, ANLN and LAMC2). High expression of these genes had shorter overall survival. CONCLUSIONS: The expression of DSG2 is related to the tumor size, lymph node metastasis and TNM stage. Also, DSG2 predicts poor prognosis in lung adenocarcinoma.

A five-long non-coding RNA signature with the ability to predict overall survival of patients with lung adenocarcinoma.

An increasing number of studies have indicated that the abnormal expression of certain long non-coding RNAs (lncRNAs) is linked to the overall survival (OS) of patients with lung adenocarcinoma (LUAD). The aim of the present study was to establish an lncRNA signature to predict the survival of patients with LUAD. The gene expression profiles and associated clinical information of patients with LUAD were downloaded from The Cancer Genome Atlas database. The cohort was randomly sub-divided into training and verification cohorts. Univariate Cox regression analysis was performed on differentially expressed lncRNAs in the training cohort to select candidate lncRNAs closely associated with survival. Next, a risk score (RS) model consisting of 5 lncRNAs was established by multivariate Cox regression analysis on candidate lncRNAs. Using the median RS obtained from the training cohort as a cut-off point, patients were classified into high- and low-risk groups. Kaplan-Meier survival analysis revealed a significant difference in OS between high- and low-risk groups. The survival prediction ability of the 5-lncRNA signature was further tested in the verification and total cohorts. The results proved that the 5-lncRNA signature had good reliability and stability in survival prediction for patients with LUAD. The univariate Cox regression analysis for the 5-lncRNA signature in each cohort indicated that the 5-lncRNA signature was closely associated with survival. Multivariate Cox regression analysis and stratification analysis proved that the prognostic signature was an independent predictor of survival for patients with LUAD. In addition, functional enrichment analysis indicated that the 5 prognostic lncRNAs may be involved in the tumorigenesis of LUAD through cancer-associated pathways and biological processes. Taken together, the present study provided a 5-lncRNA signature that may serve as an independent survival predictor for patients with LUAD.

DHX9 inhibits epithelial-mesenchymal transition in human lung adenocarcinoma cells by regulating STAT3.

DHX9 has numerous functions regulating transcription, translation, RNA processing and transport, and DNA replication and maintenance of genomic stability. It is involved in human cancers as either an oncogene or tumor suppressor. However, its role in the progression of lung cancer and underlying mechanisms remains unclear. In this study, we demonstrated that DHX9 is overexpressed in human lung cancer tissues and serum. Also, a favorable prognosis of lung adenocarcinoma is predicted when DHX9 is at a high level. DHX9 knockdown promoted cell proliferation, migration, and invasion and inhibited apoptosis progression in A549 cells. Moreover, DHX9 knockdown led to a significant decrease of E-cadherin expression, an increase of vimentin and snail, and a significant increase in the phosphorylation of STAT3 in A549 cells. In summary, our studies identified a novel role of DHX9 in driving tumor growth and epithelial-mesenchymal transition progress of A549 cells. We propose that the STAT3 pathway may be implicated in the DHX9-related epithelial-mesenchymal transition of lung adenocarcinoma. Therefore, DHX9 may be a prognostic marker or potential therapeutic target for lung adenocarcinoma.

Five genes may predict metastasis in non-small cell lung cancer using bioinformatics analysis.

Lung cancer is one of the most common types of malignancy worldwide. The prognosis of lung cancer is poor, due to the onset of metastases. The aim of the present study was to examine lung cancer metastasis-associated genes. To identify novel metastasis-associated targets, our previous study detected the differentially expressed mRNAs and long non-coding RNAs between the large-cell lung cancer high-metastatic 95D cell line and the low-metastatic 95C cell line by microarray assay. In the present study, these differentially expressed genes (DEGs) were analyzed via bioinformatics methods, including Gene Ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. A protein-protein interaction network was subsequently constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins online database and Cytoscape software, and 17 hub genes were screened out on the basis of connectivity degree. These hub genes were further validated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) using the online Gene Expression Profiling Interactive Analysis database. A total of seven hub genes were identified to be significantly differentially expressed in LUAD and LUSC. The prognostic information was detected using Kaplan-Meier plotter. As a result, five genes were revealed to be closely associated with the overall survival time of patients with lung cancer, including phosphoinositide-3-kinase regulatory subunit 1, FYN, thrombospondin 1, nonerythrocytic α-spectrin 1 and secreted phosphoprotein 1. In addition, lung cancer and adjacent lung tissue samples were used to validate these hub genes by reverse transcription-quantitative polymerase chain reaction. In conclusion, the results of the present study may provide novel metastasis-associated therapeutic strategies or potential biomarkers in non-small cell lung cancer.

Diagnostic Value of Transthoracic Echocardiography Combined With Contrast-Enhanced Ultrasonography in Mediastinal Masses.

OBJECTIVES: Multiple types of mediastinal masses, especially masses in the anterior mediastinum, may be encountered in routine echocardiographic examinations for symptomatic or asymptomatic patients. The aim of this study was to evaluate the diagnostic value of transthoracic echocardiography combined with contrast-enhanced ultrasonography in determining the location, composition, and vascularization of mediastinal masses. METHODS: A retrospective analysis was conducted on 48 consecutive patients who first had a diagnosis of mediastinal masses by echocardiography. The location of the mass, tissue components, and relationships with the heart and great vessels were analyzed on the basis of multiple transthoracic echocardiographic views. Further contrast-enhanced ultrasonography was performed to determine the vascularization of masses in 25 patients. The clinical, computed tomographic, and histopathologic findings were all recorded and analyzed. RESULTS: The localization, ultrasonographic characteristics of the mass, degree of vascularization, and relationships with the heart and great vessels assessed on echocardiography allowed a correct diagnosis in most of the cases. CONCLUSIONS: Transthoracic echocardiography is a useful method for diagnosing mediastinal. Further contrast-enhanced ultrasonography could provide more details on the degree of vascularization, which could facilitate accurate diagnosis and differentiation diagnosis.