Correlation between carcinoembryonic antigen (CEA) expression and EGFR mutations in non-small-cell lung cancer: a meta-analysis / Correlación entre la expresión del antígeno carcinoembrionario (CEA) y las mutaciones de EGFR en el cáncer de pulmón de células no pequeñas: un metanálisis

Objectives: The purpose of this meta-analysis was to investigate the relationship between serum carcinoembryonic antigen (CEA) expression and epidermal growth factor receptor (EGFR) mutation status in non-small cell lung cancer (NSCLC). Methods: Databases such as PubMed, Cochrane, EMBASE and Google Scholar were systematically searched to identify studies assessing the association of serum CEA expression with EGFR mutations. Across 19 studies, 4168 patients were included between CEA expression and EGFR mutations odds ratio (OR) conjoint analysis of correlations. Results: Compared with CEA-negative NSCLC, CEA-positive tumors had an increased EGFR mutation rate (OR = 1.85, 95% confidence interval: 1.48–2.32, P < 0.00001). This association was observed in both stage IIIB/IV patients (OR = 1.60, 95% CI: 1.18–2.15, P = 0.002) and stage I–IIIA (OR = 1.67, 95% CI: 1.01–2.77, P = 0.05) patients. In addition, CEA expression was associated with exon 19 (OR = 1.97, 95% CI: 1.25–3.11, P = 0.003) and exon 21 (OR = 1.51, 95% CI: 1.07–2.12, P = 0.02) EGFR mutations. In ADC pathological type had also showed the correlation (OR = 1.84, 95% CI: 1.31–2.57, P = 0.0004). Conclusions: This meta-analysis indicated that serum CEA expression was associated with EGFR mutations in NSCLC patients. The results of this study suggest that CEA level may play a predictive role in the EGFR mutation status of NSCLC patients. Detecting serum CEA expression levels can give a good suggestion to those patients who are confused about whether to undergo EGFR mutation tests. Moreover, it may help better plan of the follow-up treatment.(AU)

Urinary metabolic profiles during Helicobacter pylori eradication in chronic gastritis.

BACKGROUND: Helicobacter pylori (H. pylori) infection is a major risk factor for chronic gastritis, affecting approximately half of the global population. H. pylori eradication is a popular treatment method for H. pylori-positive chronic gastritis, but its mechanism remains unclear. Urinary metabolomics has been used to elucidate the mechanisms of gastric disease treatment. However, no clinical study has been conducted on urinary metabolomics of chronic gastritis. AIM: To elucidate the urinary metabolic profiles during H. pylori eradication in patients with chronic gastritis. METHODS: We applied LC-MS-based metabolomics and network pharmacology to investigate the relationships between urinary metabolites and H. pylori-positive chronic gastritis via a clinical follow-up study. RESULTS: Our study revealed the different urinary metabolic profiles of H. pylori-positive chronic gastritis before and after H. pylori eradication. The metabolites regulated by H. pylori eradication therapy include cis-aconitic acid, isocitric acid, citric acid, L-tyrosine, L-phenylalanine, L-tryptophan, and hippuric acid, which were involved in four metabolic pathways: (1) Phenylalanine metabolism; (2) phenylalanine, tyrosine, and tryptophan biosynthesis; (3) citrate cycle; and (4) glyoxylate and dicarboxylate metabolism. Integrated metabolomics and network pharmacology revealed that MPO, COMT, TPO, TH, EPX, CMA1, DDC, TPH1, and LPO were the key proteins involved in the biological progress of H. pylori eradication in chronic gastritis. CONCLUSION: Our research provides a new perspective for exploring the significance of urinary metabolites in evaluating the treatment and prognosis of H. pylori-positive chronic gastritis patients.

Correlation between carcinoembryonic antigen (CEA) expression and EGFR mutations in non-small-cell lung cancer: a meta-analysis.

OBJECTIVES: The purpose of this meta-analysis was to investigate the relationship between serum carcinoembryonic antigen (CEA) expression and epidermal growth factor receptor (EGFR) mutation status in non-small cell lung cancer (NSCLC). METHODS: Databases such as PubMed, Cochrane, EMBASE and Google Scholar were systematically searched to identify studies assessing the association of serum CEA expression with EGFR mutations. Across 19 studies, 4168 patients were included between CEA expression and EGFR mutations odds ratio (OR) conjoint analysis of correlations. RESULTS: Compared with CEA-negative NSCLC, CEA-positive tumors had an increased EGFR mutation rate (OR = 1.85, 95% confidence interval: 1.48-2.32, P < 0.00001). This association was observed in both stage IIIB/IV patients (OR = 1.60, 95% CI: 1.18-2.15, P = 0.002) and stage I-IIIA (OR = 1.67, 95% CI: 1.01-2.77, P = 0.05) patients. In addition, CEA expression was associated with exon 19 (OR = 1.97, 95% CI: 1.25-3.11, P = 0.003) and exon 21 (OR = 1.51, 95% CI: 1.07-2.12, P = 0.02) EGFR mutations. In ADC pathological type had also showed the correlation (OR = 1.84, 95% CI: 1.31-2.57, P = 0.0004). CONCLUSIONS: This meta-analysis indicated that serum CEA expression was associated with EGFR mutations in NSCLC patients. The results of this study suggest that CEA level may play a predictive role in the EGFR mutation status of NSCLC patients. Detecting serum CEA expression levels can give a good suggestion to those patients who are confused about whether to undergo EGFR mutation tests. Moreover, it may help better plan of the follow-up treatment.

Bridging Component Strategy in Phosphomolybdate-Based Sensors for Electrochemical Determination of Trace Cr(VI).

Rapid and sensitive electrochemical determination of trace carcinogenic Cr(VI) pollutants remains an urgent and important task, which requires the development of active sensing materials. Herein, four cases of reduced phosphomolybdates with formulas of the (H2bib)3[Zn(H2PO4)]2{Mn[P4Mo6O31H7]2}·6H2O (1), (H2bib)2[Na(H2O)]2[Mn(H2O)]2{Mn[P4Mo6O31H6]2}·5H2O (2), (H2bib)3[Mo2(µ2-O)2(H2O)4]2{Ni[P4Mo6O31H2]2}·4H2O (3), and (H2bib)2{Ni[P4Mo6O31H9]2}·9H2O (4) (bib = 4,4'-bis(1-imidazolyl)-biphenyl) were hydrothermally synthesized under the guidance of a bridging component strategy, which function as effective electrochemical sensors to detect trace Cr(VI). The difference of hybrids 1-4 is in the inorganic moiety, in which the reduced phosphomolybdates {M[P4MoV6O31]2} (M{P4Mo6}2) exhibited different arrangements bridged by different cationic components ({Zn(H2PO4)} subunit for 1, [Mn2(H2O)2]4+ dimer for 2, and [MoV2(µ2-O)2(H2O)4]6+ for 3). As a result, hybrids 1 and 3 display noticeable Cr(VI) detection activity with low detection limits of 14.3 nM (1.48 ppb) for 1 and 6.61 nM (0.69 ppb) for 3 and high sensitivities of 97.3 and 95.3 µA·mM-1, respectively, which are much beyond the World Health Organization's detection threshold (0.05 ppm) and superior to those of the contrast samples (inorganic Mn{P4Mo6}2 salt and hybrid 4), even the most reported noble-metal catalysts. This work supplies a prospective pathway to build effective electrochemical sensors based on phosphomolybdates for environmental pollutant treatment.

Taurine promotes muscle fiber type transformation through CaN/NFATc1 signaling in porcine myoblasts.

This study investigated the effect of taurine (TAU) on the muscle fiber type transformation in porcine myoblasts and its molecular mechanisms. The findings revealed that TAU augmented the protein expression of slow MyHC and the enzyme activities of oxidative metabolism markers like malate dehydrogenase and succinic dehydrogenase. Conversely, it curtailed the expression of fast MyHC and glycolytic metabolism enzyme activity of lactate dehydrogenase. Moreover, TAU elevated the expression of genes associated with oxidative fiber while diminishing the expression of those linked to glycolytic fibers, suggesting that TAU promoted the muscle fiber type transformation from glycolytic fiber to oxidative fiber. Additionally, TAU notably enhanced the expression of key molecules of calcineurin (CaN)/nuclear factor of activated T cells c1 (NFATc1) signaling and the CaN activity in porcine myoblasts. However, CaN inhibitor cyclosporine A abolished these effects induced by TAU. Our results indicated that TAU regulated the muscle fiber type transformation from glycolytic to oxidative fiber by activation of CaN/NFATc1 signaling.

Dietary Taurine Supplementation Improves the Meat Quality, Muscle Fiber Type, and Mitochondrial Function of Finishing Pigs.

This study investigated the effects of dietary supplementation with taurine (TAU) on the meat quality, muscle fiber type, and mitochondrial function of finishing pigs. The results demonstrated that TAU significantly increased the a* value while decreasing b*45 min, L*24 h, and drip loss24 h and drip loss48 h in the longissimus dorsi (LD) muscle. Dietary supplemented with TAU reduced the content of lactate and the glycolytic potential (GP) in the LD muscle. Dietary supplemented with TAU enhanced the oxidative fiber-related gene expression as well as increased succinic dehydrogenase and malate dehydrogenase activities while reducing lactate dehydrogenase activity. Furthermore, dietary supplementation with TAU increased the contents of mtDNA and ATP and mitochondrial function-related gene expression. Moreover, TAU enhanced the mRNA expressions of calcineurin (CaN) and nuclear factor of activated T cells c1 (NFATc1) and protein expressions of CNA and NFATc1. The results indicate that dietary TAU supplementation improves meat quality and mitochondrial biogenesis and function and promotes muscle fiber-type conversion from the glycolytic fiber to the oxidative fiber via the CaN/NFATc1 pathway.

The diagnostic value of CT-guided percutaneous puncture biopsy of pulmonary ground-glass nodules: a meta-analysis.

BACKGROUND: More and more pulmonary ground-glass nodules (GGNs) are screened with the extensive usage of low-dose computed tomography (CT). The need of CT-guided percutaneous puncture biopsy of GGN remains controversial. PURPOSE: To explore the diagnostic accuracy of CT-guided percutaneous puncture biopsy of GGNs. MATERIAL AND METHODS: We searched PubMed, EMBASE, the Cochrane Library, and CNKI. Included studies reported the puncture biopsy results of pulmonary GGNs, including the number of true positive (TP), false positive (FP), true negative (TN), and false negative (FN) cases. After evaluating the studies, statistical analysis, and quality assessment, the pooled diagnostic sensitivity (SEN), specificity (SPE), and diagnostic odds ratio (DOR) were calculated. The summary receiver operating characteristic (SROC) curve was constructed and the area under the curve (AUC) was calculated. Subgroup analysis was performed according to whether spiral CT or fluoroscopy-guided CT was used in the study. RESULTS: This meta-analysis included 14 studies with a total of 759 patients (702 samples). The pooled SEN, SPE, and DOR of CT-guided puncture biopsy of pulmonary GGNs were 0.91 (95% confidence interval [CI] = 0.89-0.94), 0.99 (95% CI = 0.95-1.00), and 138.72 (95% CI = 57.98-331.89), respectively. The AUC was 0.97. CONCLUSION: Our results indicated that CT-guided puncture biopsy of GGNs has high SEN, SPE, and DOR, which proved that CT-guided puncture biopsy was a good way to determine the pathological nature of GGN.

Comparison of CT-Guided Core Needle Biopsy in Pulmonary Ground-Glass and Solid Nodules Based on Propensity Score Matching Analysis.

Purpose: To compare the diagnostic accuracy and safety of computed tomography (CT)-guided core needle biopsy (CNB) between pulmonary ground-glass and solid nodules using propensity score matching (PSM) method and determine the relevant risk factors. Methods: This was a single-center retrospective cohort study using data from 665 patients who underwent CT-guided CNB of pulmonary nodules in our hospital between May 2019 and May 2021, including 39 ground-glass nodules (GGNs) and 626 solid nodules. We used a 1:4 PSM analysis to compared the diagnostic yields and complications rates of CT-guided CNB between 2 groups. Results: After PSM, 170 cases involved in the comparison (34 GGNs vs 136 solid nodules) were randomly matched (1:4) by patient demographics, clinical history, lesion characteristics, and procedure-related factors. There was no statistically significant difference in the diagnostic yields and complications rates between 2 groups. Significant pneumothorax incidence increase was noted at small lesion size, deep lesion location, and traversing interlobar fissure (P < .05). Post-biopsy hemorrhage was a protective factor for pneumothorax (P < .05). The size/proportion of consolidation of GGN did not influence the diagnostic accuracy and complication incidence (P > .05). Conclusions: The accuracy and safety of CT-guided CNB were comparable for ground-glass and solid nodules and the size/proportion of consolidation of GGN may be not a relevant risk factor. The biopsy should avoid traversing interlobar fissure as far as possible. Smaller lesion size and deeper lesion location may lead to higher pneumothorax rate and post-biopsy hemorrhage may be a protective factor for pneumothorax.

Development and Validation of a Concise Prediction Scoring System for Asian Lung Cancer Patients with EGFR Mutation Before Treatment.

Purpose We aimed to determine the epidermal growth factor receptor (EGFR) genetic profile of lung cancer in Asians, and develop and validate a non-invasive prediction scoring system for EGFR mutation before treatment. Methods This was a single-center retrospective cohort study using data of patients with lung cancer who underwent EGFR detection (n = 1450) from December 2014 to October 2020. Independent predictors were filtered using univariate and multivariate logistic regression analyses. According to the weight of each factor, a prediction scoring system for EGFR mutation was constructed. The model was internally validated using bootstrapping techniques and temporally validated using prospectively collected data (n = 210) between November 2020 and June 2021.Results In 1450 patients with lung cancer, 723 single mutations and 51 compound mutations were observed in EGFR. Thirty-nine cases had two or more synchronous gene mutations. We developed a scoring system according to the independent clinical predictors and stratified patients into risk groups according to their scores: low-risk (score <4), moderate-risk (score 4-8), and high-risk (score >8) groups. The C-statistics of the scoring system model was 0.754 (95% CI 0.729-0.778). The factors in the validation group were introduced into the prediction model to test the predictive power of the model. The results showed that the C-statistics was 0.710 (95% CI 0.638-0.782). The Hosmer-Lemeshow goodness-of-fit showed that χ2 = 6.733, P = 0.566. Conclusions The scoring system constructed in our study may be a non-invasive tool to initially predict the EGFR mutation status for those who are not available for gene detection in clinical practice.

Bioinformatics Analysis and Experimental Study of Exonuclease 1 Gene in Lung Adenocarcinoma.

The objective of this study is to examine the role of Human Exonuclease 1(EXO1) gene in the diagnosis and prognosis of lung adenocarcinoma (LUAD), and predict the signal pathways EXO1 involved in. The clinical parameters and EXO1 expression datasets of LUAD patients were obtained from The Cancer Genome Atlas (TCGA), Oncomine and Gene Expression Omnibus (GEO) database. Wilcoxon rank-sum test was performed to determine whether EXO1 expression was upregulated in LUAD. The correlation between EXO1 expression and clinicopathological parameters was analyzed by Chi-square test, and Kaplan-Meier survival analysis and COX regression models were adopted to analyze and verify the correlation of EXO1 expression with OS of LUAD patients for the exploration of prognostic value of EXO1 in LUAD patients. The signaling pathway related to EXO1 was predicted by gene set enrichment analysis (GSEA). In addition, sera from LUAD patients and healthy subjects were collected, and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was conducted to detect EXO1 expression. EXO1 expression was upregulated in LUAD patients with respect to normal individuals. EXO1 expression was negatively correlated with the prognosis and thus could independently predict the prognosis of LUAD patients. EXO1 gene was involved in 128 signal pathways, of which 9 pathways may be closely related. EXO1 was highly expressed in the blood of LUAD patients. High EXO1 expression can serve as an independent risk factor for poor prognosis, and the expression of serum EXO1 has certain diagnostic value for LUAD.

Effect of dietary L-theanine supplementation on skeletal muscle fiber type transformation in vivo.

The aim of this study was to investigate the effect of dietary L-theanine supplementation on skeletal muscle fiber type transition in mice. Our data indicated that dietary 0.15% L-theanine supplementation significantly increased the mRNA expression levels of muscle fiber type related genes (MyHC I, MyHC IIa, PGC-1α, Sirt1, Tnnt1, Tnnc1, Tnni1, MEF2C) and the protein expression levels of MyHC IIa, myoglobin, PGC-1α, Sirt1 and Troponin I-SS, but significantly decreased the mRNA and protein expression levels of MyHC IIb. Dietary 0.15% L-theanine supplementation significantly increased the activities of SDH and MDH and decreased the activity of LDH. Furthermore, immunofluorescence demonstrated that dietary 0.15% L-theanine supplementation significantly increased the percentage of type I fibers, and significantly decreased the percentage of type II fibers. In addition, we found that dietary 0.15% L-theanine supplementation increased the fatigue-resistant, antioxidant capacity, mitochondrial biogenesis, and function in skeletal muscle of mice. Furthermore, dietary 0.15% L-theanine supplementation significantly increased the mRNA levels of prox1, CaN and NFATc1, the protein levels of prox1, CNA and NFATc1 and the activity of CaN in GAS muscle when compared with the control group. These results indicated that dietary L-theanine supplementation promoted skeletal muscle fiber transition from type II-type I, which might be via activation of CaN and/or NFATc1 signaling pathway.

A Predictive Model to Differentiate Between Second Primary Lung Cancers and Pulmonary Metastasis.

RATIONALE AND OBJECTIVES: To develop and validate a nomogram for differentiating second primary lung cancers (SPLCs) from pulmonary metastases (PMs). MATERIALS AND METHODS: A total of 261 lesions from 253 eligible patients were included in this study. Among them, 195 lesions (87 SPLCs and 108 PMs) were used in the training cohort to establish the diagnostic model. Twenty-one clinical or imaging features were used to derive the model. Sixty-six lesions (32 SPLCs and 34 PMs) were included in the validation set. RESULTS: After analysis, age, lesion distribution, type of lesion, air bronchogram, contour, spiculation, and vessel convergence sign were considered to be significant variables for distinguishing SPLCs from PMs. Subsequently, these variables were selected to establish a nomogram. The model showed good distinction in the training set (area under the curve = 0.97) and the validation set (area under the curve = 0.92). CONCLUSION: This study found that the nomogram calculated from clinical and radiological characteristics could accurately classify SPLCs and PMs.

Radiomics Study for Discriminating Second Primary Lung Cancers From Pulmonary Metastases in Pulmonary Solid Lesions.

BACKGROUND: The objective of this study was to assess the value of quantitative radiomics features in discriminating second primary lung cancers (SPLCs) from pulmonary metastases (PMs). METHODS: This retrospective study enrolled 252 malignant pulmonary nodules with histopathologically confirmed SPLCs or PMs and randomly assigned them to a training or validation cohort. Clinical data were collected from the electronic medical records system. The imaging and radiomics features of each nodule were extracted from CT images. RESULTS: A rad-score was generated from the training cohort using the least absolute shrinkage and selection operator regression. A clinical and radiographic model was constructed using the clinical and imaging features selected by univariate and multivariate regression. A nomogram composed of clinical-radiographic factors and a rad-score were developed to validate the discriminative ability. The rad-scores differed significantly between the SPLC and PM groups. Sixteen radiomics features and four clinical-radiographic features were selected to build the final model to differentiate between SPLCs and PMs. The comprehensive clinical radiographic-radiomics model demonstrated good discriminative capacity with an area under the curve of the receiver operating characteristic curve of 0.9421 and 0.9041 in the respective training and validation cohorts. The decision curve analysis demonstrated that the comprehensive model showed a higher clinical value than the model without the rad-score. CONCLUSION: The proposed model based on clinical data, imaging features, and radiomics features could accurately discriminate SPLCs from PMs. The model thus has the potential to support clinicians in improving decision-making in a noninvasive manner.

Risk Factor Analysis and Nomogram Construction for Non-Survivors among Critical Patients with COVID-19.

The outbreak of the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, occurred in China in December 2019. This disease has caused more than 70,000 deaths worldwide. We intend to analyze the risk factors of death and establish a prognosis nomogram for critical patients with COVID-19. We analyzed the clinical data of COVID-19 patients in Zhongnan Hospital of Wuhan University who were in the critical state before March 20, 2020. Data were collected on admission and compared between survivors and non-survivors and analyzed by univariable and multivariable logistic regression analyses. Finally, 104 patients were included, 50 of whom died. Age (odds ratio, OR 5.73 [95% confidence interval, CI, 1.14-28.81]), chest tightness (OR 5.50 [95% CI, 1.02-9.64]), AST (OR 6.57 [95% CI, 1.33-32.48]), and blood urea nitrogen (5.59 [95% CI, 1.05-29.74]) at admission were considered predictors of the risk of death in critical patients and were selected to construct the nomogram. Subsequently, we established a nomogram model and validated it. The sensitivity and specificity of the nomogram were 96.0% and 74.1%, respectively. The area under the curve was 0.893 (95% CI, 0.807-0.980).

Role of Thrombospondin-1 and Nuclear Factor-κB Signaling Pathways in Antiangiogenesis of Infantile Hemangioma.

BACKGROUND: Propranolol is the first-line drug for treatment of infantile hemangioma. However, its mechanism of action remains unclear. Nuclear factor-κB is highly expressed in tumors, directly or indirectly promoting angiogenesis. Thrombospondin-1 is the most important antiangiogenesis protein in vivo. These proteins mediate signaling pathways, probably playing an important role in hemangioma treatment. This study explored the synergistic regulation of thrombospondin-1 and nuclear factor-κB signaling pathways in the treatment of hemangioma with propranolol. METHODS: The hemangioma-derived endothelial cells were sorted out from the specimens of proliferative hemangioma by flow cytometry. Furthermore, a BALB/c nude mouse hemangioma model was established. Viability and proliferation of hemangioma-derived endothelial cells and the role of thrombospondin-1 and nuclear factor-κB signaling pathways were observed after propranolol administration in vitro and in vivo. RESULTS: The expression of thrombospondin-1 and its receptor CD36 in hemangioma-derived endothelial cells gradually increased with the increase in propranolol concentration, whereas the expression of nuclear factor-κBp65, phosphorylated inhibitor of κB alpha (p-IκBα), and phosphorylated inhibitor of nuclear factor-κB kinase beta (p-IκKß) weakened gradually (p < 0.05). In vivo, the tumors shrank gradually after propranolol treatment, with an increase in thrombospondin-1 and CD36 and a decrease in nuclear factor-κBp65, p-IκBα, and p-IκKß (p < 0.05). Glucocorticoid improved the antiangiogenesis mediated by thrombospondin-1/CD36 and inhibited the angiogenesis mediated by nuclear factor-κB/IκB (p < 0.05). Negative regulation occurred between the two signaling pathways. CONCLUSION: The treatment of infantile hemangioma with propranolol is promising to promote thrombospondin-1-mediated antiangiogenesis and to block nuclear factor-κB-mediated angiogenesis.

Comprehensive investigating of cytokine and receptor related genes variants in patients with chronic hepatitis B virus infection.

BACKGROUND & AIMS: Chronic hepatitis B virus (HBV) infection is a global health problem and the outcome are associated with both viral factors and host genetic factors. High Throughput Sequencing (HTS) technology were used to identify variants associated with liver disease. METHODS: Fifty-five Chronic hepatitis B (CHB) patients, fifty-three self-healing HBV (SH) patients and 53 healthy controls (HC) were recruited, 404 cytokine and cytokine receptor related genes were captured and sequenced at high depth (>900X), both variant (Fischer's exact test, P value < 0.05) and gene (SKAT-O gene level test, adjust P value < 0.05) level association were used to identify variants and genes associated with CHB. RESULTS: Total 5083 variants have been detected, fifty-four variants were found associated with CHB, most (29/32) variants were located in HLA region, including HLA-B, HLA-C, HLA-DQA1, HLA-DQB1, HLA-DQB2, HLA-DRB1 and HLA-DRB5. Several missense variants were found associated with CHB, including p.E226K in PVR (poliovirus receptor), p.E400A and p.C431R in IL4R (interleukin 4 receptor). Four variants located in 3'UTR (untranslated region) have also been found associated with CHB. CONCLUSION: Our study revealed that high through target region sequencing, combined with association analysis at variant and gene level, would be a good way to found variants and genes associated with CHB even at small sample size. Our data implied that chronic hepatitis B patients who carry these variants need intensive monitoring.

Comprehensive investigation of cytokine- and immune-related gene variants in HBV-associated hepatocellular carcinoma patients.

Host genotype may be closely related to the different outcomes of Hepatitis B virus (HBV) infection. To identify the association of variants and HBV infection, we comprehensively investigated the cytokine- and immune-related gene mutations in patients with HBV associated hepatocellular carcinoma (HBV-HCC). Fifty-three HBV-HCC patients, 53 self-healing cases (SH) with HBV infection history and 53 healthy controls (HCs) were recruited, the whole exon region of 404 genes were sequenced at >900× depth. Comprehensive variants and gene levels were compared between HCC and HC, and HCC and SH. Thirty-nine variants (adjusted P<0.0001, Fisher's exact test) and 11 genes (adjusted P<0.0001, optimal unified approach for rare variant association test (SKAT-O) gene level test) were strongly associated with HBV-HCC. Thirty-four variants were from eight human leukocyte antigen (HLA) genes that were previously reported to be associated with HBV-HCC. The novelties of our study are: five variants (rs579876, rs579877, rs368692979, NM_145007:c.*131_*130delTG, NM_139165:exon5:c.623-2->TT) from three genes (REAT1E, NOD-like receptor (NLR) protein 11 (NLRP11), hydroxy-carboxylic acid receptor 2 (HCAR2)) were found strongly associated with HBV-HCC. We found 39 different variants in 11 genes that were significantly related to HBV-HCC. Five of them were new findings. Our data implied that chronic hepatitis B patients who carry these variants are at a high risk of developing HCC.

Mir-192 suppresses apoptosis and promotes proliferation in esophageal aquamous cell caicinoma by targeting Bim.

MicroRNAs (miRNAs) are small, non-coding RNAs of endogenous origin. Accumulating studies have shown aberrant miRNA expression plays an important role in many tumor types. However, the mechanisms by which miRNAs regulate esophageal squamous cell carcinoma (ESCC) development remain poorly understood. In the present study, we assayed expression level of miR-192 in ESCC tissues and cell lines by real-time PCR, and defined the target gene and biological function by luciferase reporter assay, Western blot and apoptosis assay. We first verified that the expression level of miR-192 was significantly increased in ESCC tissues and cancer cells. Moreover, miR-192 over-expression inhibited cells apoptosis and promoted ESCC cells proliferation. We further demonstrated that miR-192 directly targeted 3'-UTR of Bim gene, and inhibited its protein expression. Importantly, Bim could reduce ESCC cells apoptosis ability induced by miR-192. These data suggest an important role of miR-192 in the molecular etiology of ESCC and implicate the potential application of miR-192 in ESCC therapy.

MiR-133a suppresses the migration and invasion of esophageal cancer cells by targeting the EMT regulator SOX4.

MicroRNAs (miRNAs) are small, non-coding RNAs which can function as oncogenes or tumor suppressor genes in human cancers. In the present study, we demonstrated that the expression ofmiR-133a was dramatically decreased in examined esophageal squamous cell carcinoma (ESCC) cell lines and clinical ESCC tissue samples. Additionally, miR-133a expression was inversely correlated with tumor progression in ESCCs. We have found that over-expression of miR-133a significantly suppressed the proliferation, migration and invasion of ESCC cells in vitro. miR-133a over-expression also significantly suppressed the aggressive phenotype of ESCC in vivo, suggesting that miR-133a may function as a novel tumor suppressor. Further studies indicated that the EMT-related transcription factor Sox4 was a direct target gene of miR-133a, evidenced by the direct binding of miR-133a with the 3'UTR of Sox4. Notably, the EMT marker E-cadherin or vimentin, a downstream of Sox4, was also down-regulated or upregulated upon miR-133a treatment. We have also shown that over-expressing or silencing Sox4 was able to elevate or inhibit the migration and invasion of ESCC cells, similar to the effect of miR-133a on the ESCC cells. Moreover, knockdown of Sox4 reversed the enhanced migration and invasion mediated by anti-miR-133a. These results demonstrate that miR-133a acts as a tumor suppressor in ESCC through targeting Sox4 and the EMT process. miR-133a may serve as a potential target in the treatment of human esophageal cancer.

[Effect of Long Non-coding RNA SPRY4-IT1 on Invasion and Migration of A549 Cells].

BACKGROUND AND OBJECTIVE: The abnormal expression of human long chain non encoding RNA gene is related to many kinds of tumors. The aim of this study is to investigate the expression of long non-coding RNA maternally expressed gene 3 (SPRY4-IT1) in lung cancer (A549) cells, and to observe the effect of SPRY4-IT1 on the invasion and migration of A549 cells. METHODS: The levels of SPRY4-IT1 in A549 was detected by Real-time PCR. The effects of SPRY4-IT1 on the invasion and migration of A549 cell were analyzed by MTT and Transwell assay. The expression of matrix metalloproteinase (MMP) family proteins was determined by Western blot. RESULTS: The invasion and migration of A549 cells were increased after SPRY4-IT1 over-expression. The cell spaces were narrower after SPRY4-IT1 over expression in the wound healing assay. Transwell assays showed that the numbers of transmembrane A549 cells were significantly higher in SPRY4-IT1 over expression group than that in control group (P<0.05). Meanwhile, over expression of SPRY4-IT1 reduced the expression of MMP-2 and MMP-9. CONCLUSIONS: Over expression of SPRY4-IT1 enhanced the invasion and migration of A549 cells. MMP-2 and MMP-9 might play an important role in this regulation.
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