Myocardial metastasis from ZEB1-and TWIST-positive spindle cell carcinoma of the esophagus:A case report

BACKGROUND Metastatic cardiac tumors are known to occur more frequently than primary cardiac tumors,however,they often remain asymptomatic and are commonly dis-covered on autopsy.Malignant tumors with a relatively high frequency of cardiac metastasis include mesothelioma,melanoma,lung cancer,and breast cancer,whereas reports of esophageal cancer with cardiac metastasis are rare.CASE SUMMARY The case of a 60-year-old man who complained of dysphagia is presented.Upper gastrointestinal endoscopy showed a submucosal tumor-like elevated lesion in the esophagus causing stenosis.Contrast-enhanced computed tomography showed left atrial compression due to the esophageal tumor,multiple liver and lung metastases,and a left pleural effusion.Pathological examination of a biopsy speci-men from the esophageal tumor showed spindle-shaped cells,raising suspicion of esophageal sarcoma.The disease progressed rapidly,and systemic chemotherapy was deemed necessary,however,due to his poor general condition,adminis-tration of cytotoxic agents was considered difficult.Given his high Combined Positive Score,nivolumab was administered,however,the patient soon died from the disease.The autopsy confirmed spindle cell carcinoma(SCC)of the esophagus and cardiac metastasis with similar histological features.Cancer stem cell markers,ZEB1 and TWIST,were positive in both the primary tumor and the cardiac metastasis.CONCLUSION To the best of our knowledge,there have been no prior reports of cardiac metastasis of esophageal SCC.This case highlights our experience with a patient with esophageal SCC who progressed rapidly and died from the disease,with the autopsy examination showing cardiac metastasis.

Diagnosing upper tract urothelial carcinoma: A review of the role of diagnostic ureteroscopy and novel developments over last two decades

Objective: The role of ureteroscopy in the diagnosis of upper tract urothelial carcinoma is yet to be fully determined. We aimed to provide an up to date evaluation of its role and the emerging technologies in the field.Methods: A literature search of the last two decades (from 24th May, 2001 to 24th May, 2021) was carried out identifying 147 papers for potential inclusion within this narrative review.Results: Diagnostic ureteroscopy is undeniably useful in its ability to visualise and biopsy indeterminate lesions, and to risk stratify malignant lesions that may be suitable for kidney sparing surgery. However, an increased risk of intravesical recurrence following nephroureterectomy when a prior diagnostic ureteroscopy has been performed, inadequate sampling at biopsy, complications from the procedure, and difficult ureteric access are all potential drawbacks. Furthermore, whilst generally an accurate diagnostic procedure, it risks missing carcinoma in-situ lesions. Despite this, evidence shows that routine use of ureteroscopy changes the management of patients in a large proportion of cases, preventing unnecessary surgery or facilitating kidney sparing surgery. The overall rate of complications is low, and improved biopsy techniques and the use of tissue biomarkers for improved staging and grading are encouraging. The risks of delays to definitive management and post-ureteroscopy intravesical recurrence do not seem to affect survival, and trials are in progress to determine whether intravesical therapy can mitigate the latter. Further promising techniques are being investigated to improve shortcomings, particularly in relation to improved diagnosis of carcinoma in situ and preoperative staging.Conclusion: Ureteroscopy has a role in the diagnosis of upper tract malignancy, though whether it should be used routinely is yet to be determined.

MTHFR C677T polymorphisms are associated with aberrant methylation of the IGF-2 gene in transitional cell carcinoma of the bladder

The purpose of this study was to determine the relationship between methylation status of the insulin-like growth factor 2 （IGF-2） gene and methylenetetrahydrofolate reductase （MTHFR） C677T gene polymorphisms in bladder transitional cell carcinoma tissues in a Chinese population. The polymorphisms of the folate metabolism enzyme gene MTHFR were studied by restrictive fragment length polymorphism （RFLP）, PCR-based methods of DNA methylation analysis were used to detect the CpG island methylation status of the IGF-2 gene. The association between the methylation status of the IGF-2 gene and clinical characteristics, as well as MTHFR C677T polymorphisms, was analyzed. Aberrant hypomethylation of the IGF-2 gene was found in 68.3% bladder cancer tissues and 12.4% normal bladder tissues, respectively, while hypomethylation was not detected in almost all normal bladder tissues. The hypomethylation rate of the IGF-2 gene in cancer tissues was significantly higher in patients with lymph node metastasis than in those without lymph node metastasis （46.3% vs 17.2%, P = 0.018）. No association was found between aberrant DNA methylation and selected factors including sex, age, tobacco smoking, alcohol consumption and green tea consumption. After adjusting for potential confounding variables the variant allele of MTHFR C677T was found to be associated with hypomethylation of the IGF-2 gene. Compared with wildtype CC, the odds ratio was 4.33 （95% CI=1.06-10.59） for CT and 4,95 （95% CI=1.18-12.74） for TT. MTHFR 677 CC and CT genotypes might be one of the reasons that cause abnormal hypomethylation of the IGF-2 gene, and the aberrant CpG island hypomethylation of the IGF-2 gene may contribute to the genesis and progression of bladder transitional cell carcinoma.

Research on the prognosis of different types of microvessels in bladder transitional cell carcinoma

BACKGROUND At present,there is controversy on the role of microvessel density(MVD)in tumors as a prognostic indicator of bladder transitional cell carcinoma(BTCC).However,the MVD in tumors is simply classified based on the expression of several different vascular markers,which has not been related to analytical research on the prognosis of patients with BTCC.AIM To explore the classification of blood vessels in tumors and studied the relationship between MVD and the prognosis of patients with BTCC.METHODS The tissue mass was detected by tissue microarray and immunohistochemical analysis with monoclonal antibodies against CD31,CD34,CD105,and vascular smooth muscle actin to investigate the MVD in BTCC.The measurement data are expressed as the mean±SD.The difference between the groups was analyzed by the t-test,the counting data were analyzed byχ2 test.The Kaplan-Meier survival curve was estimated by the product-limit method.The log-rank time-series test was employed to compare the tumor-free survival curves.RESULTS The MVD was closely related to the pathological grade,invasive depth,and prognosis of BTCC.Significant differences were found between grade I and grade II,grade II and grade III,superficial and invasive type,and the tumor-free survival group and the recurrence or metastasis group(P<0.01).Multivariate analysis showed that undifferentiated MVD was an independent prognostic factor for patient survival time.An inverse correlation between undifferentiated tumor MVD and differentiated tumor MVD in BTCC was also shown.CONCLUSION The classification of blood vessels in BTCC could act as an important prognostic indicator and may also be of great significance in the treatment of cancer.

The Expression and Significance of KAl1 and Ki67 in Bladder Transitional Cell Carcinoma

OBJECTIVE To explore the expression and significance of the tumor metastatic suppressor gene the KAI1 and Ki67 antigen in bladder transitional cell carcinoma （BTCC）. METHODS Two-stepped immuno-histochemical staining was used to detect the expression of the KAI1 protein and Ki67 antigen. The reverse transcription polymerase chain reaction （RT-PCR） was used to detect the KAI1 mRNA in 54 BTCC specimens and 32 normal bladder counterparts. 13-actin was the internal control. RESULTS The KAI1 protein was mainly expressed on cell membranes at cell-to-cell borders, with uniform and continuous staining in normal bladder transitional epithelium. However, the number of positive-staining cells was greatly decreased in BTCC epithelium, and with an increase in the stage and Grade and appearance of lymph node metastasis the staining was non-uniform and discontinuous. The Ki67 antigen was expressed in the nucleus, and with an increase in the stage and Grade and appearance of lymph node metastasis, the Ki67 expression increased. The Ki67 antigen was negatively related to the expression of KAI1 （P〈0.01）.The expression level of KAI1 mRNA was much greater in normal bladder transitional epithelium compared to BTCC, moreover, with an increase in the Grade, infiltration depth and appearance of lymph node metastasis, the expression of KAI1 mRNA was reduced. CONCLUSION The expression of KAI1 protein may be used as a prognostic marker to indicate the degree of infiltration and metastasis. Measurement of KAI1 and Ki67 expression together may be helpful in evaluating the metastatic potential and prognosis of BTCC patients.

Simultaneous occurrence of transitional cell carcinoma and renal cell carcinoma in the same kidney:a casereport and review of the literature

This article reports a case of simultaneous occurrence of 2 primary renal tumors of different histology, a transitional cell carcinoma and a renal cell carcinoma. in the same kidney. The histological, immunohistochemical and ultrastructural changes of the tumors were described. A review of the literature to date revealed this case to be rare. only 24 other cases were reported previously.

Expression of connexin43 and its correlation with the expressions of Bcl-2 and Bax proteins in transitional cell carcinoma of the bladder

Objective: To study the expression of connexin43 (Cx43) gene and its correlation with the apoptosis related genes Bcl-2 and Bax in transitional cell carcinoma of the bladder (BTCC), and to investigate the role of Cx43 in the BTCC. Methods: Reverse transcription polymerase chain reaction was used to detect the expression of Cx43 mRNA and immunocytochemistry technique was used to detect the expressions of Bcl-2 and Bax proteins in 60 cases of BTCC tissues, and compared with that of 15 cases of pericancerous tissues and 15 cases of normal bladder tissues. Results: The positive expression rate of Cx43 mRNA in 60 cases of BTCC tissues was 43.33% which was significantly lower than that in pericancerous tissues (73.33%) and normal tissues (100%) (χ2 = 17.58, P < 0.01). The expression of Cx43 had significant negative correlation with the pathological degree and lymph node metastasis of BTCC (χ2 = 9.33 and 9.74, respectively, P < 0.01). However, no correlation was found between the expression and patient sex, age, clinical staging and diameter and growth pattern of BTCC (P > 0.05). Expression of Cx43 negatively correlated with Bcl-2 protein (r = -0.63, P < 0.01) and positively correlated with Bax protein (r = 0.52, P < 0.01). Conclusion: The down-regulated expression of Cx43 gene was closely associated with the development, invasion and metastasis of BTCC. It could be used as a prognostic indicator for BTCC. Cx43 gene may have antagonistic effects with Bcl-2 gene and synergic with Bax gene in the initiation and progression of BTCC.

Transitional cell carcinoma of the ovary – A case report with review of literature

Transitional cell carcinoma （TCC） of the ovary is a rare and recently recognized subtype of ovarian epithelial cancer. We presented the first case report from our Institute （Sheri Kashmir Instiute of Medical Sciences, Srinagar, India）, which was initially rnisdiagnosed as stromal cell carcinoma （granulosa cell tumour）, and on review of histopathology with immunohistochemistry, the diagnosis of TCC of the ovary was established. The aim of this article was to describe the typical case of primary TCC of the ovary and to review the literature for information on TCC management.

Neoadjuvant Chemotherapy for Transitional Cell Carcinoma of the Bladder： A Single Centre Experience

Urothelial cancers usually recur distantly rather than loco-regionally. In patients with pT2 and pT3/pT4 tumors, local recurrence has been observed in 3-4% and 11-16%, respectively, whereas distant failure has occurred in 10-27% and 19-35%, respectively. Despite local therapy most patients with muscle invasive transitional cell carcinoma （TCC） of the bladder die of systemic relapse, indicating a need for effective adjunctive systemic treatment. We determined whether neoadjuvant chemotherapy improved overall survival. This study evaluated the role of neoadjuvant combination chemotherapy with gemcitabine/cisplatin （GC） in improving the outcome of this group of patients. A total of 44 patients （84% Male, 16% Female） with newly diagnosed bladder cancer （T3-4, N0-2, M0） were subjected to initial 3 cycles of GC, then managed according to response. Patients were assessed clinically after each cycle and by Interim CT scan after 3 cycles of chemotherapy and those who achieved complete or partial response underwent radical cystectomy. We enrolled 63 patients, 19 of whom were found to be ineligible; thus, 44 were assigned to receive neoadjuvant chemotherapy followed by surgery. Average size of the largest tumor was greater that 30mm in 77% patients. According to Computed Tomographic findings 70% patients belonged to Stage T4A. The overall response rate to GC was 50%, and incomplete response was achieved in 25% whereas 25% patients were lost to follow up. Twenty two patients who had complete response, underwent cystectomy and diversion. It was observed that those patients who underwent radical cystectomy with ureterosigmoidostomy had an increased serum creatinine in comparison to patients who had ileal conduit. The size of the effect is modest and combination chemotherapy can be administered safely without adverse outcomes resulting in delayed local therapy. Further efforts to identify the patients most likely to benefit from neoadjuvant therapy are necessary to optimize its use.

Clinical Significance of Cytokeratin 19 and Cytokeratin 20 in Predicting Recurrence of Bladder Transitional Cell Carcinoma

Objective： To investigate the expressions of cytokeratin 19 （CK19） and cytokeratin 20 （CK20） in bladder transitional cell carcinoma （TCC） and their clinical significance. Methods： The expression of CK19 and CK20 was detected in 54 cases of TCC by immunohistochemical methods and image processing techniques. Results： The expression of CK19 and CK20 was significantly stronger in the recurrent group than in the non-recurrent group （P〈0.01, P〈0.001, respectively）. Conclusion： The expression of CK19 and CK20 was obviously related with biological behaviors of TCC, suggesting that CK19 and CK20 could be used to predict the recurrence of TCC.

Relationship of A,B,H blood group antigens with pathomorphological grading and prognosis of transitional-cell carcinoma of the urinary bladder

After being labelled with monoclonal antibodies against A,B, H blood group antigens,100 specimens of transitional-cell carcinoma of the urinary bladder were studied with ABC immunohistochemical technique and the cases were followed up.It was found that the overall positive rate of A,B,H antigens was 63%. The mortality rate and recurrence were significantly lower in the positive group than in the negative group(P<0.01)and 5-years survival rate was higher in the positive than in the negative(P<0.01).The findings suggest that the expression of blood group antigens is more effective for the prognosis of transitional-cell bladder carcinoma than the pathomorphological grading.

Clinical implications of single cell sequencing for bladder cancer

Bladder cancer(BC)is the 10th most common cancer worldwide,with about 0.5 million reported new cases and about 0.2 million deaths per year.In this scoping review,we summarize the current evidence regarding the clinical implications of single-cell sequencing for bladder cancer based on PRISMA guidelines.We searched PubMed,CENTRAL,Embase,and supplemented with manual searches through the Scopus,and Web of Science for published studies until February 2023.We included original studies that used at least one single-cell technology to study bladder cancer.Forty-one publications were included in the review.Twenty-nine studies showed that this technology can identify cell subtypes in the tumor microenvironment that may predict prognosis or response to immune checkpoint inhibition therapy.Two studies were able to diagnose BC by identifying neoplastic cells through single-cell sequencing urine samples.The remaining studies were mainly a preclinical exploration of tumor microenvironment at single cell level.Single-cell sequencing technology can discriminate heterogeneity in bladder tumor cells and determine the key molecular properties that can lead to the discovery of novel perspectives on cancer management.This nascent tool can advance the early diagnosis,prognosis judgment,and targeted therapy of bladder cancer.

Long-term follow-up of Ta transitional cell carcinoma of bladder after treatment of TURBt plus intravesical therapy

To stduy the association between the prognosis of Ta transitional cell carcinoma (TCC) of the bladder and risk-related factors.Methods A total of 88 cases (62 males and 26 females;mean age,61 years;age range,41-81 years) of initial T.TCC of the bladder treated with transurethral resection of bladder tumor (TURBt) plus intravesical chemotherapy or immunotherapy were enrolled.Among them,there were 26 cases of G1,61 cases of G2 and 1 case of G3.For tumor site,62 cases (16 cases of G1,45 of G2,1 of G3) had single tumor and 26 cases (10 cases of G1,16 of G2) had multi-site tumors.The mean follow-up was 113 months (range,56-168 months).The tumor grade,original tumor number and their association with the recurrence and progression of this type of TCC were retrospectively analyzed.Results The overall recurrence rate (RR) was 60% (53/88).In single tumor group,RR of G1 cases was 25% (4/16);RR of G2 cases was 62% (28/45) and the total RR was 52% (32/62).In multi-site tumor group,RR of G1 cases was 80% (8/10),RR of G2 cases was 75% (12/16) and the total RR was 77% (20/26).The RR of multi-site tumor group was significantly higher than that of single tumor group (P<0.01).In single tumor group,RR of G2 cases was significantly higher than that of G1 cases (P<0.001).In multi-site tumor group,there was no association of RR with tumor grade.There was no progression in G1 tumor cases.The progression rate was 42.5% (17/40) in G2 tumor cases;among them,30% (12/40) progressed to T1G2 tumors and 12.5% (5/40) progressed to T2G2 tumors.The RR of cases who received thiotepa,mitomycin and BCG were 75% (12/16),68% (30/44) and 40% (11/27),respectively.Tumor specific mortality was 1.14% (1/88,a T2G3 case).Conclusion The multi-site Ta TCC of the bladder has relatively higher RR and greater chance of progression after the treatment of TURBt plus intravesical chemotherapy or immunotherapy,especially in the poor differentiated tumors,thus active treatment and close follow-up are essential in clinical practice.9 refs.

Application of single-cell RNA sequencing in head and neck squamous cell carcinoma

Single-cell RNA sequencing has been broadly applied to head and neck squamous cell carcinoma(HNSCC) for characterizing the heterogeneity and genomic mutations of HNSCC benefiting from the advantage of single-cell resolution. We summarized most of the current studies and aimed to explore their research methods and ideas, as well as how to transform them into clinical applications. Through single-cell RNA sequencing, we found the differences in tumor cells’ expression programs and differentiation tracks. The studies of immune microenvironment allowed us to distinguish immune cell subpopulations, the extensive expression of immune checkpoints, and the complex crosstalk network between immune cells and non-immune cells. For cancerassociated fibroblasts(CAFs), single-cell RNA sequencing had made an irreplaceable contribution to the exploration of their differentiation status, specific CAFs markers, and the interaction with tumor cells and immune cells. In addition, we demonstrated in detail how single-cell RNA sequencing explored the HNSCC epithelial-tomesenchymal transition(EMT) model and the mechanism of drug resistance, as well as its clinical value.

Expression and Significance of PTEN in Bladder Transitional Cell Carcinoma

Objective： To explore the expression of anti-oncogene PTEN in bladder transitional cell carcinoma and its clinical significance. Methods： Using immunohistochemical S-P methods, the expression of PTEN gene was detected in 62 specimens of bladder cancer and 18 specimens of normal bladder tissue. Results： In the 62 bladder cancers, the positive rate of PTEN was 53.2% （33/62）. All 18 normal bladder tissues were positive for the PTEN expression. The expression of PTEN was negatively correlated to tumor grades （P〈0.05）. Conclusion： The reduced expression of PETN might play an important role in carcinogenesis and progression of bladder cancer. Detection of PTEN might be useful for judgement of tumor development and prognosis.

Expression of KAI1/CD82 and MRP-1/CD9 in Transitional Cell Carcinoma of Bladder

The expression of KAI1/CD82 and MRP-1/CD9 in transitional cell carcinoma of bladder （TCCB） and its clinical significance were investigated. Immunohistochemistry was used to detect KAI1/CD82 and MRP-1/CD9 protein expression in 52 TCCB specimens. Correlation between the expression of KAI1/CD82 and MRP-1/CD9 to clinicopathologic factors was statistically analyzed. The results showed that the positive rate of KAI1/CD82 and MRP-1/CD9 in TCCB was 50% and 61.5%, respectively. The MRP-1/CD9 and KAI1/CD82 expression was significantly associated with grade of TCCB （P〈0.05）, but no correlation was found between MRP-1/CD9 or KAI1/CD82 expression and clinical stage of TCCB （P〉0.05）. The expression level of MRP-1/CD9 and KAI1/CD82 in recurrent TCCB samples was lower than that in non-recurrent samples （P〈0.05）. Meanwhile, the correlation between the KAI1/CD82 expression and MRP-1/CD9 expression was statistically significant （r=0.316, P〈0.05）. It was concluded that KAI1/CD82 and MRP-1/CD9 expression may be important prognostic indicators and potentially useful for assessing the biological behavior of TCCB.

Squamous cell carcinoma of the oral cavity and circulating tumour cells

Due to a lack of substantial improvement in the outcome of patients suffering from oral squamous cell carcinoma(OSCC) during the past decades, current staging methods need to be revised. This disease is associated with poor survival rates despite considerable advances in diagnosis and treatment. The early detection of metastases is an important indicator of survival, prognosis and relapse. Therefore, a better understanding of the mechanisms underlying metastasis is crucial. Exploring alternative measures apart from common procedures is needed to identify new prognostic markers. Similar to previous findings predominantly for other solid tumours, recently published studies demonstrate that circulating tumour cells(CTCs) and disseminated tumour cells(DTCs) might serve as prognostic markers and could supplement routine staging in OSCC. Thus, the detection of CTCs/DTCs is a promising tool todetermine the individual need for therapeutic intervention. Encouraging results and new approaches point to the future use of targeted therapies for OSCC, an exceedingly heterogeneous subgroup of head and neck cancer. This review focuses on summarising technologies currently used to detect CTCs/DTCs. The translational relevance for OSCC is highlighted. The inherent challenges in detecting CTCs/DTCs will be emphasised.

Plasmacytoid Transitional Cell Carcinoma of Bladder： A Clinico-pathological Study and Review of Literatures

Objective： To study the pathologic features of plasmacytoid transitional cell carcinoma of the bladder, and to analyze the diagnostic features, criteria for differential diagnosis and the clinical significance of the tumor. Methods： Two cases of bladder plasmacytoid transitional cell carcinoma were studied. Routine paraffin sections with HE staining, Pap smear and immunohistochemistry by S-P method were observed under a light microscope. Pathological and clinical data were analyzed by comparison with early reported cases in literatures. Results： A characteristic feature of this tumor was of deep invasion in the lamina propria and/or muscularis propria, in addition to the component of carcinoma in situ in the mucosa, when tumors were diagnosed. The histological pattern and cytological features showed similarity to a plasmacytoid tumor. The tumor cells were strongly positive for AE1/AE3, CEA and CK18. The prognosis appeared to be worse than ordinary transitional cell carcinoma. Conclusion： The plasmacytoid transitional cell carcinoma of bladder is rare but has typical pathological, immunohistological and clinical features. Pathologists should be aware of this kind of primary tumor of bladder.

RECURRENCE RISK FACTORS IN PATIENTS WITH TRANSITIONAL CELL CARCINOMA OF BLADDER

Objective： To study recurrence factors and set up a model to evaluate the prognosis of patients with bladder cancer. Methods： An analysis on recurrence-related factors was made by Cox＇s proportional hazards model analysis and logistic multiple linear regression model analysis in 212 patients with transitional cell carcinoma treated surgically from 1995-2001. These factors included clinical and pathologic figures. Results： The most important factor is metastasis to the regional lymph nodes, the Hazards ratio is 6.6 （P=0.0004）, followed by multiple tumors （Hr=2.255, P〈0.0001）, tumor in trigone and bladder neck （Hr=2.053, P〈0.0001）, stage （Hr=2.057, P〈0.0001）, grade （Hr=1.569, P=0.0081）, intravesical chemotherapeutic instillations （Hr-0.559, P=0.0011） and hematuria （Hr=0.762, P=0.0076）. A predicting equation was established, and the predicting values were calculated according to the individual features of patients. The predicting and actual values were compared, and the sensitivity, specificity and overall concordance were 83.5%, 67.6% and 80.1% respectively. Conelusion：The evaluation of prognosis could be made quite accurately based on these factors.

Inhibition of bromodomain-containing protein 4 enhances the migration of esophageal squamous cell carcinoma cells by inducing cell autophagy

BACKGROUND Esophageal squamous cell carcinoma(ESCC),the predominant type of esophageal cancer,has a 5-year survival rate less than 20%.Although the cause of poor prognosis is the high incidence and mortality of ESCC,the high rate of metastasis after esophageal cancer surgery is the main cause of death after the surgery.Bromodomain-containing protein 4(BRD4),an epigenetic reader of chromatinacetylated histones in tumorigenesis and development,plays an essential role in regulating oncogene expression.BRD4 inhibition and BRD4 inhibition-based treatment can potentially suppress ESCC growth.However,the effects and mechanisms of action of BRD4 on ESCC cell migration remain unclear.AIM To explore the effect of BRD4 on cell migration of ESCC in vitro and its possible molecular mechanism.METHODS Human ESCC cell lines KYSE-450 and KYSE-150 were used.The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay was performed to examine cell proliferation,and the transwell migration assay was conducted to test ESCC cell migration.JQ1,a BRD4 inhibitor,was applied to cells,and BRD4 siRNA was transfected into ESCC cells to knockdown endogenous BRD4.GFP-RFP-LC3 adenovirus was infected into ESCC cells to evaluate the effect of JQ1 on autophagy.Western blotting was performed to determine the protein levels of BRD4,E-cadherin,vimentin,AMP-activated protein kinase(AMPK),and p-AMPK.RESULTS BRD4 was either downregulated by small interfering RNA or pretreated with JQ1 in ESCC cells,leading to increased tumor migration in ESCC cells in a dose-and time-dependent manner.Inhibition of BRD4 not only significantly suppressed cell proliferation but also strongly increased cell migration by inducing epithelial-mesenchymal transition(EMT).The protein expression of vimentin was increased and E-cadherin decreased in a dose-dependent manner,subsequently promoting autophagy in KYSE-450 and KYSE-150 cells.Pretreatment with JQ1,a BRD4 inhibitor,inhibited BRD4-induced LC3-II activation and upregulated AMPK phosphorylation in a dosedependent manner.Additionally,an increased number of autophagosomes and autolysosomes were observed in JQ1-treated ESCC cells.The autophagy inhibitor 3-methyladenine(3-MA)reversed the effects of BRD4 knockdown on ESCC cell migration and blocked JQ1-induced cell migration.3-MA also downregulated the expression of vimentin and upregulation E-cadherin.CONCLUSION BRD4 inhibition enhances cell migration by inducing EMT and autophagy in ESCC cells via the AMPK-modified pathway.Thus,the facilitating role on ESCC cell migration should be considered for BRD4 inhibitor clinical application to ESCC patients.