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To improve the recognition accuracy of badminton players’ swing movements, this study proposes a single inertial sensor based method for badminton swing movement recognition. This article proposes a badminton racket-mounted data gathering system with a single inertial sensor and proposes a real-time motion data flow-based window segmentation technique to capture motion data. On this basis, a two-layer classifier recognition model based on C4.5 Decision Tree (C4.5 T) algorithm and Random Forest (RF) method is constructed to recognize swing technical actions. Using the C4.5 T to identify the swing style of athletes; The RF method is used to recognize the swing technical action. The final experiment showed that the method studied achieved a recognition accuracy of 95.36% for six common swing movements. The proposed model has good application prospects in the recognition of badminton swing movements. However, due to the limitations of the experimental conditions, the recognition effect of this method on more complex swing movements needs to be further verified.

Thyroid hormone (T3) is essential for development and organ metabolism in all vertebrates. T3 has both genomic and nongenomic effects on target cells. While much has been learnt on its genomic effects via T3 receptors (TRs) in vertebrate development, mostly through TR-knockout and knockin studies, little is known about the effects of T3 on gene expression in animals in the absence of TR. We have been studying Xenopus metamorphosis as a model for mammalian postembryonic development, a period around birth when plasma T3 level peaks and many organs/tissues mature into their adult forms. We have recently generated TR double knockout (TRDKO) Xenopus tropicalis animals. This offers an opportunity to compare the effects of T3 on global gene expression in tadpole tissues in the presence or absence of TR.We analyzed the effects of T3 on gene expression in tadpole tail and intestine by using RNA-seq analysis on wild-type and TRDKO tadpoles with or without T3 treatment.We observed that removing TRs reduced the number of genes regulated by T3 in both organs. Gene Ontology (GO) and KEGG pathway analyses revealed that T3 affected distinct biological processes and pathways in wild-type and TRDKO tadpoles. Many GO terms and KEGG pathways were enriched among genes regulated in wild-type tissues are likely involved in mediating the effects of T3 on metamorphosis, e.g., those related to development, stem cells, apoptosis, and cell cycle/cell proliferation. However, such GO terms and pathways were not enriched among T3-regulated genes in TRDKO tadpoles. Instead, in TRDKO tadpoles, GO terms and pathways related to "metabolism" and "immune response" were highly enriched among T3-regulated genes. We further observed strong divergence in the TR-independent, nongenomic effects of T3 in the intestine and tail.Our data suggest that T3 have distinct and organ-dependent effects on gene expression in developing tadpoles. The TR-mediated effects are consistent with the metamorphic changes, in agreement with the fact that TR is necessary and sufficient to mediate the effects of T3 on metamorphosis. T3 appears to have a major effect on metabolism and immune response via TR-independent nongenomic processes.

Systemic sclerosis (SSc) is a clinically heterogeneous fibrotic disease with no effective treatment. Myofibroblasts are responsible for unresolving synchronous skin and internal organ fibrosis in SSc, but the drivers of sustained myofibroblast activation remain poorly understood. Using unbiased transcriptome analysis of skin biopsies, we identified the downregulation of SPAG17 in multiple independent cohorts of patients with SSc, and by orthogonal approaches, we observed a significant negative correlation between SPAG17 and fibrotic gene expression. Fibroblasts and endothelial cells explanted from SSc skin biopsies showed reduced chromatin accessibility at the SPAG17 locus. Remarkably, mice lacking Spag17 showed spontaneous skin fibrosis with increased dermal thickness, collagen deposition and stiffness, and altered collagen fiber alignment. Knockdown of SPAG17 in human and mouse fibroblasts and microvascular endothelial cells was accompanied by spontaneous myofibroblast transformation and markedly heightened sensitivity to profibrotic stimuli. These responses were accompanied by constitutive TGF-β pathway activation. Thus, we discovered impaired expression of SPAG17 in SSc and identified, to our knowledge, a previously unreported cell-intrinsic role for SPAG17 in the negative regulation of fibrotic responses. These findings shed fresh light on the pathogenesis of SSc and may inform the search for innovative therapies for SSc and other fibrotic conditions through SPAG17 signaling.

Ropy Latilactobacillus plantarum NA exhibits antibacterial and antioxidant activities and effects on RAW 264.7 macrophages.

A carbon dots with intrinsic nucleolus-targeting capability and superior biocompatibility was synthesized and employed for dynamic fluorescence imaging of nucleolus in living cells.

Recently, novel 2D InGeTe3 has been successfully synthesized and attracted attention due to its excellent properties.

Thyroid hormone (T3) is essential for normal development and metabolism, especially during postembryonic development, a period around birth in mammals when plasma T3 levels reach their peak. T3 functions through two T3 receptors, TRα and TRβ. However, little is known about the tissue-specific functions of TRs during postembryonic development because of maternal influence and difficulty in manipulation of mammalian models. We have studied Xenopus tropicalis metamorphosis as a model for human postembryonic development. By using TRα knockout (Xtr·thra

In recent years, reports regarding stimulator of interferon genes (STING) and the progression of colorectal cancer (CRC) have emerged rapidly, yet their association remains controversial. This research was aimed to provide an insight into the prognostic biomarker and therapeutic target significance of STING in CRC.CRC Cell lines of HCT116 and SW480, as well as 32 paired CRC specimens were chosen for this study. STING expressions were examined by immunohistochemistry to evaluate the correlation with clinicopathological factors. Data analysis of STING expressions in colon cancer and rectal cancer were performed using The Cancer Genome Atlas (TCGA) database. siRNA was transfected into cell lines for knocking down the expression of STING. Transwell assay was employed to evaluate cell migration and invasiveness. CCK-8 assay was used for assessing the change of cell proliferation. Drug sensitive test was involved to evaluate drug resistance of cell lines. Gene Set Enrichment Analysis (GSEA) was applied for exploring potential downstream mechanism of STING in CRC progression and Western blotting is used for mechanism validation.In the thirty-two paired CRC and adjacent normal tissues, we found a significant up-regulated in STING expression with immunohistochemical staining in cancer tissues compared with adjacent normal tissues (P0.01), which was correlated with the tumor-node-metastasis (TNM) stage of patients (P=0.028). Meanwhile, GESA enrichment analysis indicated a remarkable change in mTOR signaling following STING regulation. In HCT116 and SW480 cell lines of CRC, When STING was down-regulated, its biological behavior of cell viability, cell invasion and drug sensitivity to 5-fluorouracil were significantly reduced (P0.05), we also observed the up-regulation of P-AMPK (P0.05) and down-regulation of p-mTOR (P0.05).STING expressions was significantly up-regulated in CRC tissues. Expression of STING was correlated with the TNM stage of patients. STING is found to promote cell proliferation, invasion ability and drug resistance mediating AMPK-mTOR signaling in CRC. STING could be a promising target for the sensitization of chemotherapy and inhibits CRC progression.

Hepatitis B virus (HBV) is a major risk factor for the development and progression of hepatocellular carcinoma (HCC). It has been reported that viral infection can interfere with the expression of cellular microRNA (miRNA) to affect oncogenesis. In this study, we showed that miR-520c-3p was upregulated in liver tumor specimens, and we revealed that HBV infection enhanced the expression of miR-520c-3p through the interaction of viral protein HBV X protein (HBx) with transcription factor CREB1. We further showed that miR-520c-3p induced by HBV transfection/infection caused epithelial-mesenchymal transition (EMT). Using the miRNA target prediction database miRBase and luciferase reporter assays, we identified PTEN as a novel target gene of miR-520c-3p and miR-520c-3p directly targeted PTEN's 3'-untranslated region. Moreover, we discovered that HBV promoted EMT via the miR-520c-3p-PTEN to activate AKT-NFκB signaling pathway, leading to increased HCC migration and invasion. Importantly, miR-520c-3p antagomir significantly represses invasiveness in HBx-induced hepatocellular xenograft models. Our findings indicate that miR-520c-3p is a novel regulator of HBV and plays an important role in HCC progression. It may serve as a new biomarker and molecular therapeutic target for HBV patients.

To analyze the outcomes of Supera stent deployment in Chinese patients with atherosclerotic femoropopliteal artery (FPA) disease in a real-world setting.This retrospective cohort study collected and analyzed the medical records of 246 consecutive patients who received Supera stents for FPA disease at the China Academy of Chinese Medical Sciences Xiyuan Hospital between February 2017 and December 2019. All study patients underwent balloon angioplasty and were treated with Supera stents (Abbott Vascular, Santa Clara, CA, USA). The primary outcome was the rate of primary patency 12 months after discharge.The analyses included 246 consecutive patients and 260 lesions. The mean ± SD age was 73.2 ± 9.9 years and most patients (60.2%) were males. Of the 260 treated lesions, Supera stents were deployed in eight (3.1%) cases after a previous stent fracture. Critical limb ischemia was diagnosed in 87.3% of the limbs, and 84 (32.3%) and 83 (31.5%) cases were classified as TransAtlantic Inter-Society Consensus (TASC) C and D, respectively. Most of the lesions were in situ (80.8%) and located in the superficial femoral artery (45.0%) or the FPA (45.8%). The mean lesion length was 147.7 mm. Nominal deployment (-10 to 10% compression) was the most common deployment scenario (84.1%). The 1-year primary patency rate was 80.6%. Lesions that occurred as restenosis (odds ratio [OR]: = 3.34, 95% confidence interval [CI]: 1.03-10.85, P = 0.045) or in-stent restenosis (OR: = 2.88, 95% CI: 1.03-8.07, P = 0.045) were independently associated with occlusion or stenosis after stent deployment. No stent fracture was observed in this study.Our study indicates that the use of Supera stents is feasible for the treatment of Chinese patients with FPA disease. The long-term results reveal high primary patency.

Visual recognition is currently one of the most important and active research areas in computer vision, pattern recognition, and even the general field of artificial intelligence. It has great fundamental importance and strong industrial needs, particularly the modern deep neural networks (DNNs) and some brain-inspired methodologies, have largely boosted the recognition performance on many concrete tasks, with the help of large amounts of training data and new powerful computation resources. Although recognition accuracy is usually the first concern for new progresses, efficiency is actually rather important and sometimes critical for both academic research and industrial applications. Moreover, insightful views on the opportunities and challenges of efficiency are also highly required for the entire community. While general surveys on the efficiency issue have been done from various perspectives, as far as we are aware, scarcely any of them focused on visual recognition systematically, and thus it is unclear which progresses are applicable to it and what else should be concerned. In this survey, we present the review of recent advances with our suggestions on the new possible directions towards improving the efficiency of DNN-related and brain-inspired visual recognition approaches, including efficient network compression and dynamic brain-inspired networks. We investigate not only from the model but also from the data point of view (which is not the case in existing surveys) and focus on four typical data types (images, video, points, and events). This survey attempts to provide a systematic summary via a comprehensive survey that can serve as a valuable reference and inspire both researchers and practitioners working on visual recognition problems.

Except for producing smoothing models, magnetotelluric inversion also requires focused inversion, which can image sharp boundaries and clear interfaces of electrical structures. The proposed minimum support (MS) and minimum gradient support (MGS) have good focusing ability; however, their focusing effect is highly dependent on the selection of the focusing parameter. For finding a more stable way to achieve a well-focused image, we have developed an exponential minimum support (EMS) stabilizing functional, which combines the properties of the exponential stabilizer and MS, and determined the enhanced focusing ability and smaller dependence on the magnitude of the focusing parameter. Moreover, we construct a model constraint with the hybrid stabilizing functionals EMS and the smoothest (SM) and fulfill the optimization based on Occam’s inversion scheme. Through theoretical analysis and model tests, we determine the selection schemes of the regularization parameter, weighting parameter between EMS and SM, and focusing coefficient in EMS to ensure the stability and reliability of this method. Afterward, we perform the inversions of the synthetic and field data. By comparing the inversion results of the two synthetic wedge models using hybrid EMS and SM and those obtained using other stabilizers, we determine that the hybrid method is capable of imaging sharp boundaries and is stable for a wide range of focusing parameter values. The inversion result of the COPROD2 field data set clearly images the high-conductivity anomalies at depths of 10–60 km and also depicts the highly conductive features within the upper mantle at depths greater than 100 km. The model tests and field data application verify the stability and capability of this method. Thus, this novel regularization approach provides a tool for sharp boundary inversion and a new reference model for deep structural interpretation.

BACKGROUND: Conventional ultrasound and contrast-enhanced ultrasound (CEUS) are commonly used in the diagnosis of benign and malignant thyroid nodules. However, the value of the two methods in the diagnosis of benign and malignant thyroid nodules remains controversial. METHODS: PubMed, Medline, EBSCO, Science Direct, Cochrane Library, China National Knowledge Infrastructure (CNKI) database and manual journal retrieval were searched from January 2000 to January 2022, to include research on conventional ultrasound or CEUS in the diagnosis of benign and malignant thyroid nodule related clinical studies. Meta-analysis was conducted using RevMan5.3 and Stata Corp to analyze the sensitivity and specificity of conventional ultrasound and CEUS in the diagnosis of benign and malignant thyroid nodules with 95% confidence interval (CI) as indicators. Heterogeneity of the results was evaluated by Q test and I(2) in RevMan5.3. Deek’s method was used to evaluate publication bias. RESULTS: A total of 1,378 nodules were included in 11 literatures, including 535 malignant thyroid nodules and 843 benign thyroid nodules. Heterogeneity tests conducted for CEUS diagnostic sensitivity of the 6 included literatures indicated that there was no heterogeneity among the study groups [Q=2.05, degree of freedom (df) =5.00, I(2)=0.00%, P=0.84]. The combined sensitivity was 0.87, with 95% confidence interval (CI): 0.82 to 0.90. Heterogeneity tests on the diagnostic specificity of CEUS of the six included literatures suggested that there was heterogeneity among the different study groups (Q=14.27, df =5.00, I(2)=64.96%, P=0.01). The combined specificity was 0.84 (95% CI: 0.78 to 0.89). Heterogeneity tests performed on the sensitivity of five conventional ultrasound diagnosis articles revealed that there was heterogeneity among different study groups (Q=13.62, df =4.00, I(2)=70.64%, P=0.01). The combined sensitivity was 0.86 (95% CI: 0.78 to 0.92). Heterogeneity tests on the specificity of conventional ultrasound diagnosis in five included literatures indicated that there was heterogeneity among different study groups (Q=16.94, df =4.00, I(2)=76.39%, P=0.00). The combined specificity was 0.84 (95% CI: 0.75 to 0.90). There was no bias in the included literature. DISCUSSION: The sensitivity of CEUS in the diagnosis of benign and malignant thyroid nodules was slightly higher than that of conventional ultrasound, which provides a reference for the clinical diagnosis of benign and malignant thyroid nodules.

Targeted genome editing is a powerful tool for studying gene function in almost every aspect of biological and pathological processes. The most widely used genome editing approach is to introduce engineered endonucleases or CRISPR/Cas system into cells or fertilized eggs to generate double-strand DNA breaks within the targeted region, leading to DNA repair through homologous recombination or non-homologous end joining (NHEJ). DNA repair through NHEJ mechanism is an error-prone process that often results in point mutations or stretches of indels (insertions and deletions) within the targeted region. Such mutations in embryos are germline transmissible, thus providing an easy means to generate organisms with gene mutations. However, point mutations and short indels present difficulty for genotyping, often requiring labor intensive sequencing to obtain reliable results. Here, we developed a single-tube competitive PCR assay with dual fluorescent primers that allowed simple and reliable genotyping. While we used Xenopus tropicalis as a model organism, the approach should be applicable to genotyping of any organisms.

BackgroundPrevious studies have shown that the predictive value of traditional linear (time domain and frequency domain) heart rate variability (HRV) for the survival of patients with advanced non-small cell lung cancer (NSCLC) is controversial. Nonlinear methods, based on the concept of complexity, have been used to evaluate HRV, providing a new means to reveal the physiological and pathological changes in HRV. This study aimed to assess the association between heartbeat complexity and overall survival in patients with advanced NSCLC.MethodsThis study included 78 patients with advanced NSCLC (mean age: 62.0 ± 9.3 years). A 5-min resting electrocardiogram of advanced NSCLC patients was collected to analyze the following HRV parameters: time domain indicators, i.e., standard deviation of the normal-normal intervals (SDNN) and root mean square of successive interval differences (RMSSD); frequency domain indicators, i.e., total power (TP), low frequency power (LF), high frequency power (HF), and the ratio of LF to HF (LF/HF); nonlinear HRV indicators characterizing heartbeat complexity, i.e., approximate entropy (ApEn), sample entropy (SampEn), and recurrence quantification analysis (RQA) indexes: mean diagonal line length (Lmean), maximal diagonal line length (Lmax), recurrence rate (REC), determinism (DET), and shannon entropy (ShanEn).ResultsUnivariate analysis revealed that the linear frequency domain parameter HF and nonlinear RQA parameters Lmax, REC, and DET were significantly correlated with the survival of advanced NSCLC patients (all p p ConclusionThere was an independent association between heartbeat complexity and survival in advanced NSCLC patients. The nonlinear analysis method based on RQA may provide valuable additional information for the prognostic stratification of patients with advanced NSCLC and may supplement the traditional time domain and frequency domain analysis methods.

PDF file - 1061K, S Figure 1. Down-regulation of CRT expression reduces PTP1B mRNA and protein expression in KYSE510 cells. S2. PTP1B promotes ESCC cell invasion and migration in KYSE510 cells. KYSE510 cells were transfected with PTP1B-specific siRNA (siRNA PTP1B) or non-targeting siRNA control (siRNA cont). S3. CRT regulates cell motility through PTP1B in ESCC cells. (A-C) 1x105 KYSE150 cells were seeded on 24-well plates with three replicates. S4. Cancer-inflammatory response was minimal in mouse model. S5. CRT regulates PTP1B transcription through Stat5a. S6. The expression of CRT and PTP1B in 176 ESCC tissues was evaluated by immunohistochemistry. S7. Correlation of PTP1B expression with overall survival in patients with CRT high-expressing tumors. S8. Model of CRT-dependent signaling pathway in ESCC cell metastasis. Supplementary Table 1. The candidate genes altered in CRT-siRNA KYSE150 cells as compared with non-targeting siRNA cells detected by cDNA array

Protein kinase Cι (PKCι) is an atypical PKC isoform and participates in multiple aspects of the transformed phenotype in human cancer cells. We previously reported that frequent amplification and overexpression of PKCι were correlated with lymph node metastasis in primary esophageal squamous cell carcinomas (ESCC). In the present study, short interfering RNA–mediated silencing of PKCι revealed that this enzyme was required for cell migration, invasion, and resistance to anoikis. In vivo experiments showed that PKCι suppression decreased tumor growth in esophageal cancer xenografts and lung metastases in nude mice. At the molecular level, knockdown of PKCι in suspended ESCC cells caused a decrease in S-phase kinase-associated protein 2 (SKP2) that had been reported to promote resistance to anoikis via the PI3K/AKT pathway. AKT phosphorylation was abolished after PKCι suppression, but AKT activation could be refreshed by PKCι upregulation, suggesting that PKCι enhanced cell resistance to anoikis via the PKCι-SKP2-PI3K/AKT pathway. Addition of the proteasome inhibitor MG132 prevented the decrease of SKP2 in PKCι silenced cells, and polyubiquitin-SKP2 was elevated after PKCι depletion, showing that PKCι might regulate the expression of SKP2 through the ubiquitin-proteasome pathway in suspended cells. Furthermore, overexpression of SKP2 in PKCι-downregulated cells restored cell resistance to anoikis. Most importantly, PKCι expression significantly correlated with SKP2 in 133 ESCC tissues (P = 0.031). Taken together, our data show that PKCι promotes tumorigenicity and metastasis of human esophageal cancer and that SKP2 is a candidate downstream effector of PKCι signaling in ESCC. Mol Cancer Res; 9(4); 390–402. ©2011 AACR.

Supplementary Figures S1-S5.

Calreticulin (CRT) is a Ca2+-binding chaperone protein that alters cellular Ca2+-homeostasis in the endoplasmic reticulum (ER). Previously it was shown that CRT was overexpressed in esophageal squamous cell carcinoma (ESCC), and elevated CRT expression promoted the migration and invasion of ESCC cells. In the present study, the mechanisms underlying the role of CRT in esophageal carcinoma progression were investigated. Critically, depletion of CRT or protein-tyrosine phosphatase 1B (PTP1B) reduced ESCC cell migration and metastasis to the lung, whereas restoration of PTP1B protein levels rescued cell migration in CRT-silenced cells. Knockdown of CRT decreased PTP1B protein expression by reducing phosphorylation at the Y694 site of STAT5A, whereas knockdown of PTP1B reduced ERK1/2 phosphorylation at T204. Immunohistochemical analysis of CRT and PTP1B expression in ESCC patient tissues was strongly correlated. Importantly, PTP1B expression was associated with poor survival in patients with CRT overexpression. Overall, these data indicate a novel signaling pathway connecting CRT, STAT5A, PTP1B, and ERK1/2 in the regulation of ESCC cell migration.Implications: These findings suggest that PTP1B is a downstream effector of CRT signaling, promotes tumor progression, and can potentially be used as a new drug target for ESCC. Mol Cancer Res; 11(9); 986–94. ©2013 AACR.

Effect of ANO1 on cell proliferation. Knock-down the expression of ANO1 inhibited the cell proliferation of KYSE30 (A) and KYSE510 cells (B). The absorbance at 450 nm was measured.

Amplification and overexpression of MCM7 in ESCC. A. Amplification of MCM7 in array CGH study. B. Validation of MCM7 amplification by FISH. Left: two MCM7 signals in peripheral blood cells; Middle: two MCM7 signals in ESCC cells; Right: more than four MCM7 signals in ESCC cells. C. MCM7 overexpressed in ESCC by semi-quantitative RT-PCR. D. MCM7 overexpressed in ESCC by Western blotting. E. MCM7 overexpressed in ESCC by IHC.

Frequency plot comparison analysis. A. Frequency plot comparison of ESCC with or without lymph node metastasis. B. Frequency plot comparison of ESCC at different stages.

Supplementary Figures S1-S8; Supplementary Tables S1-S4.

Purpose: To investigate the molecular mechanisms through which polo-like kinase-1 (PLK1) takes part in anoikis resistance of esophageal squamous cell carcinoma (ESCC) cells.Experimental Design: The role of PLK1 in cell anoikis resistance was examined by ectopic gene expression and siRNA-mediated knockdown. Glutathione S-transferase pull-down and co-immunoprecipitation assays were utilized to investigate PLK1-interacting proteins. Electrophoretic mobility shift assay, chromatin immunoprecipitation, and reporter gene assays were carried out to identify the transcription factors responsible for PLK1 expression during anoikis resistance.Results: We found that detachment of ESCC cells triggers the upregulation of PLK1. Elevated PLK1 expression contributes to protection against anoikis in cancer cells through the regulation of β-catenin expression. Moreover, we showed that, through direct binding to the PLK1 promoter, the NF-κB subunit RelA transcriptionally activates PLK1, which inhibits the ubiquitination and degradation of β-catenin. Inhibition of the NF-κB pathway restores the sensitivity of cancer cells to anoikis by downregulating PLK1/β-catenin expression. In addition, RelA gene amplification and protein overexpression was significantly correlated with PLK1 expression in ESCC tissues.Conclusions: Our findings suggest that upregulation of PLK1 triggered by cell detachment is regulated by RelA at the transcriptional level. PLK1 protects esophageal carcinoma cells from anoikis through modulation of β-catenin protein levels by inhibiting their degradation. Taken together, this study reveals critical mechanisms involved in the role of RelA/PLK1/β-catenin in anoikis resistance of ESCC cells. Clin Cancer Res; 17(13); 4285–95. ©2011 AACR.

Venn diagrams comparing differences in expression of our gene/microRNA expression assay and other microarray experiments. A. Comparison of differentially expressed genes in different experiments. B. Comparison of differentially expressed microRNAs in different experiments. â†', overexpressed; â†", underexpressed.

Genomic aberrations in esophgeal dysplasia and ESCC. A. Validation of 11q13.3 amplification by FISH. Left: 11q13.3 amplification detected by array CGH. Right: FISH results. B. Comparison of the number of aberrations between dysplasia and ESCC.

mRNA expression of ANO1 in ESCC cell lines. X. Name of ESCC cell lines. Y. The relative mRNA expression of ANO1 compared with GAPDH.

Purpose: Our aim was to identify frequent genomic aberrations in both esophageal squamous cell carcinoma (ESCC) and esophageal dysplasia and to discover important copy number-driving genes and microRNAs (miRNA) in ESCC.Experimental Design: We conducted array-based comparative genomic hybridization (array CGH) on 59 ESCC resection samples and 16 dysplasia biopsy samples. Expression of genes at 11q13.3 was analyzed by real-time PCR (RT-PCR) and immunohistochemistry (IHC). Integrated analysis was conducted to identify genes or miRNAs with copy number-expression correlations.Results: Array CGH identified 11 amplifications and eight homozygous deletions in ESCC. Integrated analysis of array CGH data with matched gene expression microarray data showed that 90 overexpressed genes and 24 underexpressed genes were consistent with DNA copy number changes, including 12 copy number-driving miRNAs. In esophageal dysplasia, six gains, four losses, 12 amplifications, and four homozygous deletions were detected. Amplifications of 7p11.2 and 11q13.2–11q13.3 (CCND1) and homozygous deletion at 9p21.3 (CDKN2A) were consistent genomic changes in both dysplasia and carcinoma. ANO1 at 11q13.3 was overexpressed at the mRNA and protein levels in tumors, and higher mRNA expression was correlated with the copy number increase. In particular, ANO1 expression was elevated in moderate dysplasia compared with normal esophageal epithelium. IHC revealed that ANO1 overexpression was positively correlated with lymph node metastasis and advanced clinical stage. Knockdown of ANO1 significantly inhibited the proliferation of KYSE30 and KYSE510 cells.Conclusion: Copy number aberrations in both esophageal dysplasia and ESCC may be useful as potential biomarkers for early detection. In addition, ANO1 may be a candidate target gene in esophageal tumorigenesis. Clin Cancer Res; 19(21); 5867–78. ©2013 AACR.

Supplement file: Materials and Methods