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To analyse the regulatory effect of Fusobacterium nucleatum (Fn) on NOD-like receptor protein 3 (NLRP3) and myeloid-derived suppressor cells (MDSCs) in oesophageal squamous cell carcinoma (ESCC) as well as its effect on cisplatin (CDDP) therapy and to explore its clinical significance. Fn infection, NLRP3 expression and MDSCs infiltration in ESCC tissues were detected by RNAscope and immunohistochemistry (IHC). The correlation between these three factors and the clinicopathological features and survival of ESCC patients was analysed. A coculture system of human peripheral blood monocytes (PBMCs) and ESCC cells was established to simulate the tumour microenvironment. In vitro and in vivo models were used to analyse the effects of Fn on the percentage of MDSCs in the coculture system and the NLRP3 expression level and CDDP sensitivity of ESCC cells. Fn infection was consistent with high NLRP3 expression and MDSCs enrichment in ESCC tissues. Moreover, the survival time of ESCC patients was significantly shortened under Fn infection, high NLRP3 expression and MDSCs enrichment. In the in vitro and in vivo models, Fn induced abundant enrichment of MDSCs by inducing high expression of NLRP3 in ESCC cells and reducing the sensitivity of ESCC cells to CDDP. Fn infection can induce high expression of NLRP3 in ESCC, lead to MDSCs enrichment, weaken the body's antitumour immunity, and lead to CDDP treatment resistance. The effective elimination of Fn and the inhibition of MDSCs enrichment may provide new strategies and treatments for ESCC. The survival of ESCC patients with Fn infection, high NLRP3 expression and MDSCs enrichment was significantly shortened. Fn infection could cause CDDP resistance in ESCC. Fn could induce the enrichment of MDSCs in the tumour microenvironment by activating NLRP3 in ESCC cells. [ABSTRACT FROM AUTHOR]

To analyze the correlation between the inducing effect of Fusobacterium nucleatum (Fn) on the surface expression of the inhibitory receptor KIR2DL1 on CD8+ T cells in oesophageal squamous cell carcinoma (ESCC) and the clinicopathological features and survival prognosis and to explore its clinical significance. The inducing effect of Fn on CD8+ T cell surface inhibitory receptor KIR2DL1 expression was analyzed in a coculture system of human CD8+ T cells and ESCC cells infected with Fn. Fn infection and the expression of KIR2DL1 on CD8+ T cells were detected by RNAscope and immunohistochemistry in ESCC tissues, and the correlations between the inducing effect of Fn on KIR2DL1 expression on CD8+ T cells and clinicopathological features were analyzed. COX regression was used to analyze the influence of each factor on the prognosis of ESCC. Survival curves were plotted by the Kaplan–Meier method, and the effect of KIR2DL1 induction on survival time was analyzed by the log-rank test. In the coculture system, KIR2DL1 expression on the surface of CD8+ T cells increased with increasing Fn infection time. In ESCC tissues, Fn infection was significantly correlated with high KIR2DL1 expression on CD8+ T cells. The Fn + CD8+KIR2DL1 positive patients were predominantly males who were smokers and alcohol drinkers. Moreover, patients with Fn infection were characterized by poor tumour differentiation, advanced clinical stage, and a short survival time. Meanwhile, Fn + CD8+KIR2DL1 positive group was independent risk factor affecting the prognosis of ESCC patients. Long-term drinking and smoking lead to an extremely unhealthy oral environment in which Fn infection and colonization are more likely to occur, thus inducing high expression of KIR2DL1 on the surface of CD8+ T cells, which can weaken the antitumour immune response and promote the malignant progression of ESCC. Fn induced high expression of KIR2DL1 CD8+ T cells in a time-dependent manner. Fn can reduce the response of tumour cells to CDDP. The inducing effect of Fn on CD8+ T cell surface KIR2DL1 expression was significantly associated with the poor prognosis of ESCC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Esophageal squamous cell carcinoma (ESCC) is a familiar lethal malignance. Increasing evidence has disclosed that lncRNA is involved in tumorgenesis and progression in various tumor types. However, the current understanding of angiogenesis-related lncRNAs (ARlncRNAs) involved in ESCC remains evasive. We developed and validated a six-DEARlncRNA risk score system among the GSE53624 and GSE53622 set, aiming to identify the novel prognostic targets for ESCC. Our results showed that the six-DEARlncRNA could be used as an effective independent prognostic factor of ESCC. Furthermore, the six-DEARlncRNA biomarkers mainly participated in regulation of the skin and epidermis development, and these processes protected the body from environmental insults and may have been involved in the progression of ESCC. In conclusion, this study showed that the six-DEARlncRNA signature could be used as an independent prognostic factor and may be a valuable target for treatment options in ESCC. Esophageal squamous cell carcinoma (ESCC) is a lethal gastrointestinal malignancy worldwide. We aimed to identify an angiogenesis-related lncRNAs (ARlncRNAs) signature that could predict the prognosis in ESCC. The GSE53624 and GSE53622 datasets were derived from the GEO database. The differently expressed ARlncRNAs (DEARlncRNAs) were retrieved by the weighted gene co-expression network analysis (WGCNA), differential expression analysis, and correlation analysis. Optimal lncRNA biomarkers were screened from the training set and the six-DEARlncRNA signature comprising AP000696.2, LINC01711, RP11-70C1.3, AP000487.5, AC011997.1, and RP11-225N10.1 could separate patients into high- and low-risk groups with markedly different survival. The validation of the reliability of the risk model was performed by the Kaplan-Meier test, ROC curves, and risk curves in the test set and validation set. Predictive independence analysis indicated that risk score is an independent prognostic biomarker for predicting the prognosis of ESCC patients. Subsequently, a ceRNA regulatory network and functional enrichment analysis were performed. The IC50 test revealed that patients in the high-risk group were resistant to Gefitinib and Lapatinib. Finally, the six DEARlncRNAs were detected by qRT-PCR. In conclusion, we demonstrated a novel ARlncRNA signature as an independent prognostic factor to distinguish the risk of ESCC patients and benefit the personalized clinical applications. [ABSTRACT FROM AUTHOR]

This study is aimed at assessing the sintilimab-based regimens' safety and efficacy for advanced esophageal cancer (EC) treatment in the real world. Cases of advanced EC treated with sintilimab-based regimens in the Anyang Tumor Hospital between 1 January 2020 and 1 August 2021 were retrospectively examined. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR), objective response rate (ORR), and adverse events (AEs) were evaluated. Among the 50 included patients, the median PFS was 11.3 months (95% CI: 5.0-17.6 months), and the 1-year PFS rate was 49.2%. The median OS was not reached, and the 1-year OS rate was 67.1%. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) were seen in 14% (n = 7), 46% (n = 23), 32% (n = 16), and 8% (n = 4) of the 50 patients, respectively. Therefore, the ORR and DCR were 60% (30/50) and 92% (46/50), respectively. The CR rate of patients with radiotherapy was higher than that without radiotherapy (25% vs. 3.8%, P = 0.031). The 1-year OS rate was higher in patients with radiotherapy than in patients without radiotherapy (85.9% vs. 53.2%, P = 0.020). The most observed AEs included anemia, decrease in white blood cell count, nausea/vomiting, and hypoproteinemia. Sintilimab-based regimens achieved good disease control and tolerance for treating advanced EC in the real world. Combined radiotherapy can improve the efficacy and deserves further study. [ABSTRACT FROM AUTHOR]

This study aims to develop and validate a effective prognostic nomogram for locally advanced esophageal squamous cell carcinoma (LA-ESCC) patients undergoing concurrent chemoradiotherapy (CCRT). Retrospective analysis of 503 patients with LA-ESCC given CCRT in our hospital from 2009 to 2016 was conducted. Two-thirds of the patients were randomly assigned to the training set (n = 335), and one-third were assigned to the validation set (n = 168). In order to generate the nomogram, multivariate cox regression analysis was undertaken in the training set for uncovering significant prognostic variables for overall survival. The C -index and calibration plot were used to verify nomogram discrimination and calibration, respectively. Five independent prognostic variables were found and incorporated into a nomogram: age, N stage, location, tumor response, and MLR (monocyte/lymphocyte ratio). The C -indexes of the training set and the validation set were 0.730 and 0.745, respectively. The discrimination and calibration of this nomogram showed good predictive power in both sets. Conclusively, the proposed nomogram may be served as an effective tool for prognostic evaluation of LA-ESCC patients receiving CCRT. [ABSTRACT FROM AUTHOR]

Background: The tRNA-derived small RNAs (tsRNAs) are produced in a nuclease-dependent manner in responses to variety of stresses that are common in cancers. We focus on a cancer-enriched tsRNA signature to develop a salivary exosome-based non-invasive biomarker for human esophageal squamous cell carcinoma (ESCC). Methods: Cancer-enriched small RNAs were identified by RNA sequencing of salivary exosomes obtained from ESCC patients (n = 3) and healthy controls (n = 3) in a pilot study and further validated in discovery cohort (n = 66). A multicenter prospective observational study was conducted in two ESCC high-incidence regions (n = 320 and 200, respectively) using the newly developed biomarker signature. Results: The tsRNA (tRNA-GlyGCC-5) and a previously undocumented small RNA were specifically enriched in salivary exosomes of ESCC patients, ESCC tissues and ESCC cells. The bi-signature composed of these small RNAs was able to discriminate ESCC patients from the controls with high sensitivity (90.50%) and specificity (94.20%). Based on the bi-signature Risk Score for Prognosis (RSP), patients with high-RSP have both shorter overall survival (OS) (HR 4.95, 95%CI 2.90–8.46) and progression-free survival (PFS) (HR 3.69, 95%CI 2.24–6.10) than those with low-RSP. In addition, adjuvant therapy improved OS (HR 0.47, 95%CI 0.29–0.77) and PFS (HR 0.36, 95%CI 0.21–0.62) only for patients with high but not low RSP. These findings are consistent in both training and validation cohort. Conclusions: The tsRNA-based signature not only has the potential for diagnosis and prognosis but also may serve as a pre-operative biomarker to select patients who would benefit from adjuvant therapy. Trial registration: A prospective study of diagnosis biomarkers of esophageal squamous cell carcinoma, ChiCTR2000031507. Registered 3 April 2016 - Retrospectively registered. [ABSTRACT FROM AUTHOR]

We herein report a novel, reliable and inexpensive method for detecting esophageal cancer using blood plasma resonance Raman spectroscopy combined with multivariate analysis methods. The blood plasma samples were divided into late stage cancer group (n = 164), early stage cancer group (n = 35) and normal group (n = 135) based on clinical pathological diagnosis. Using a specially designed quartz capillary tube as sample holder, we obtained higher quality resonance Raman spectra of blood plasma than existing method. The study demonstrated that the carotenoids levels in blood plasma were reduced in esophageal cancer patients. The area under the receiver operating characteristic curve (and 95% confidence interval) calculated by wavenumber selection and principal component analysis combined with linear discriminant analysis (PC‐LDA) algorithm were 0.894 (0.858‐0.929), 0.901 (0.841‐0.960) and 0.871 (0.799‐0.942) for differentiating late cancer from normal, late cancer from early cancer, and early cancer from normal respectively. The contribution from the two carotenoids wavenumber regions of 1155 and 1515 cm−1 were more than 84.2%. The results show that the plasma carotenoids could be a potential biomarker for screening esophageal cancer using resonance Raman spectroscopy combined with wavenumber selection and PC‐LDA algorithms. [ABSTRACT FROM AUTHOR]

Background: The effect of Porphyromonas gingivalis (Pg) infection on oesophageal squamous cell carcinoma (ESCC) prognosis, chemotherapeutic efficacy, and oesophageal cancer cell apoptosis resistance and proliferation remain poorly understood.Methods: Clinicopathological data from 312 ESCC oesophagectomy patients, along with the computed tomography imaging results and longitudinal cancerous tissue samples from a patient subset (n = 85) who received neoadjuvant chemotherapy (NACT), were analysed. Comparison of overall survival and response rate to NACT between Pg-infected and Pg-uninfected patients was made by multivariate Cox analysis and Response Evaluation Criteria in Solid Tumours v.1.1 criteria. The influence of Pg on cell proliferation and drug-induced apoptosis was examined in ESCC patients and validated in vitro and in vivo.Results: The 5-year overall survival was lower in Pg-positive patients, and infection was associated with multiple clinicopathological factors and pathologic tumour, node, metastasis stage. Of the 85 patients who received NACT, Pg infection was associated with a lower response rate and 5-year overall survival. Infection with Pg resulted in apoptosis resistance in ESCC and promoted ESCC cell viability, which was confirmed in longitudinal cancerous tissue samples. Pg-induced apoptosis resistance was dependent on fimbriae and STAT3.Conclusions: Pg infection is associated with a worse ESCC prognosis, reduced chemotherapy efficacy, and can potentiate the aggressive behaviour of ESCC cells. [ABSTRACT FROM AUTHOR]

Esophageal carcinoma (EC) is a tremendous threat to human health and life worldwide. Long non-coding RNAs (lncRNAs) have been identified as crucial players in carcinomas including EC. An in-depth understanding on regulatory networks of lncRNAs contributes to the better management of EC. In this text, 2052 lncRNAs and 3240 mRNAs were found to be differentially expressed in 5 EC tumor tissues versus adjacent normal tissues by microarray analysis. Moreover, 297 carcinoma-related genes were screened out according to pathway and disease annotation analyses. In addition, 410 potential lncRNA-mRNA cis-regulation pairs and 395 lncRNA-mRNA trans-regulation pairs were screened out. Among these genes, 14 trans-regulated and 19 cis-regulated genes were found to be related with carcinomas. Additionally, 42 possible lncRNA-mRNA trans-regulation pairs and 26 cis-regulation pairs were found to be related with carcinomas. Also, 4 differentially expressed transcription factors in EC and lncRNAs possibly regulated by these transcription factors were screened out. Moreover, plenty of common upregulated or downregulated lncRNAs and mRNAs in EC were identified by comparative analysis for our microarray outcomes and previous high-throughput data. Furthermore, we demonstrated that ENST00000437781.1 knockdown inhibited cell proliferation and facilitated cell apoptosis by downregulating SIX homeobox 4 (SIX4) and ENST00000524987.1 knockdown had no influence on anoctamin 1 calcium activated chloride channel (ANO1) expression in EC cells. In conclusion, we identified some crucial lncRNAs and genes along with potential regulatory networks of lncRNAs/genes, deepening our understanding on pathogenesis of EC. [ABSTRACT FROM AUTHOR]

Background: To investigate the differences in plasma metabolomic characteristics between pathological complete response (pCR) and non-pCR patients and identify biomarker candidates for predicting the response to neoadjuvant chemoradiotherapy (nCRT) in esophageal squamous cell carcinoma (ESCC).Methods: A total of 46 ESCC patients were included in this study. Gas chromatography time-of- flight mass spectrometry (GC-TOF/MS) technology was applied to detect the plasma samples collected before nCRT via untargeted metabolomics analysis.Results: Five differentially expressed metabolites (out of 109) was found in plasma between pCR and non-pCR groups. Compared with non-pCR group, isocitric acid (p = 0.0129), linoleic acid (p = 0.0137), citric acid (p = 0.0473) were upregulated, while L-histidine (p = 0.0155), 3'4 dihydroxyhydrocinnamic acid (p = 0.0339) were downregulated in the pCR plasma samples. Pathway analyses unveiled that citrate cycle (TCA cycle), glyoxylate and dicarboxylate metabolic pathway were associated with ESCC chemoradiosensitivity.Conclusion: The present study provided supporting evidence that GC-TOF/MS based metabolomics approach allowed identification of metabolite differences between pCR and non-pCR patients in plasma levels, and the systemic metabolic status of patients may reflect the response of ESCC patient to neoadjuvant chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) are tumor cells present in the bloodstream, which originate from tumor sites, and are ultimately responsible for metastasis or relapse in several types of cancer. However, to the best of our knowledge, only a few studies have investigated these extremely rare cells in esophageal squamous cell carcinoma (ESCC). In the present study, 63 patients with ESCC and 50 healthy donors were recruited, and the potential clinical significance of CTCs was assessed using subtraction enrichment and immunostaining-fluorescence in situ hybridization. Blood samples were collected at the following times: At first diagnosis, following neoadjuvant chemoradiotherapy, 24 h and 13 days post-surgery, and every 3 months during follow-up. Cytokeratin (CK)-positive and clustered CTCs only accounted for 1% of total CTCs detected, whereas most CTCs were CK-negative aneuploid cells. Patients with ESCC (n=63) had higher CTC counts compared with healthy donors (control group; n=50) (area under curve=0.807, median CTC count, 2 vs. 0). However, there was no statistical association between CTC counts and sex, age, pathological stage, tumor location, tumor depth or lymph node involvement (P>0.05). The association of tumor development with CTC status and other circulating biomarkers was monitored in patients for a further 2 years. The results revealed that a change in CTC counts between first diagnosis and 13 days post-surgery (ΔCTC) of ≥2/7.5 ml peripheral blood could be applied for predicting progression-free survival (hazard ratio, 3.922; 95% confidence interval, 0.907–16.951; P<0.05) in patients with ESCC. In conclusion, ΔCTC evaluation may be a promising indicator for predicting tumor prognosis and the clinical efficacy of treatment in patients with ESCC. [ABSTRACT FROM AUTHOR]

Nuclear receptor coactivator 1 (NCOA1) plays crucial roles in the regulation of gene expression mediated by a wide spectrum of steroid receptors such as androgen receptor (AR), estrogen receptor α (ER α), and estrogen receptor β (ER β). Therefore, dysregulations of NCOA1 have been found in a variety of cancer types. However, the clinical relevance and the functional roles of NCOA1 in human esophageal squamous cell carcinoma (ESCC) are less known. We found in this study that elevated levels of NCOA1 protein and/or mRNA as well as amplification of the NCOA1 gene occur in human ESCC. Elevated levels of NCOA1 due to these dysregulations were not only associated with more aggressive clinic‐pathologic parameters but also poorer survival. Results from multiple cohorts of ESCC patients strongly suggest that the levels of NCOA1 could serve as an independent predictor of overall survival. In addition, silencing NCOA1 in ESCC cells remarkably decreased proliferation, migration, and invasion. These findings not only indicate that NCOA1 plays important roles in human ESCC but the levels of NCOA1 also could serve as a potential prognostic biomarker of ESCC and targeting NCOA1 could be an efficacious strategy in ESCC treatment. NCOA1 plays important roles in human ESCC, but the levels of NCOA1 also could serve as a potential prognostic biomarker of ESCC and targeting NCOA1 could be an efficacious strategy in ESCC treatment. [ABSTRACT FROM AUTHOR]

Gastric cardia adenocarcinoma (GCA), which occurs at the gastroesophageal boundary, is one of the most malignant types of cancer. Over the past 30 years, the incidence of GCA has increased by approximately sevenfold, which has a more substantial increase than that of many other malignancies. However, as previous studies mainly focus on non-cardia gastric cancer, until now, the mechanisms behind GCA remain largely unknown. MicroRNAs (miRNAs) have been shown to play pivotal roles in carcinogenesis. To gain insight into the molecular mechanisms regulated by miRNAs in GCA development, we investigated miRNA expression profiles using 81 pairs of primary GCAs and corresponding non-tumorigenic tissues. First, 21 pairs of samples were used for microarray analysis, and then another 60 pairs of samples were used for further analysis. Our results showed that 464 miRNAs (237 upregulated, 227 downregulated, false discovery rate FDR <0.05) were differently expressed between GCA and non-tumor tissues. Pearson test and pathway analysis revealed that these dysregulated miRNA correlated coding RNAs may have effects on several cancer-related pathways. Four miRNAs (miR-1244, miR-135b-5p, miR-3196, and miR-628-3p) were found to be associated with GCA differentiation. One miRNA, miR-196a-5p, was found to be associated with age of GCA onset. Further, survival analysis showed that the expression level of miR-135b-5p was associated with GCA survival. Taken together, our study first provided the genome-wide expression profiles of miRNA in GCA and will be good help for further functional studies. [ABSTRACT FROM AUTHOR]

Zinc finger E-box-binding homeobox 1 ( ZEB1) is a transcriptional factor known to repress E-cadherin promoter and thus induce EMT. Expression of ZEB-1 has in numerous cancers been associated with aggressive disease and poor clinical outcome. Our aim was to investigate the expression of ZEB1 in esophageal squamous- and small-cell carcinomas. Immunohistochemical staining was performed on tissue sections obtained from 151 patients with esophageal squamous cell carcinoma ( ESCC) and 25 patients with primary small-cell carcinoma of the esophagus ( PSCCE). Semi-quantitative analysis, and thus statistical analysis, has been accomplished on the samples. Immunohistochemistry revealed ZEB1 expression in the cytoplasm (64.9% of cases), in nuclei (11.3% of cases) and in tumor stroma (80.1% of cases) of ESCC. In PSCCE only nuclear staining (88.0% of cases) was observed. Weak cytoplasmic expression of ZEB1 in ESCC was associated with longer survival. Immunohistochemical evaluation of ZEB1 cytoplasmic expression in ESCC may have clinical prognostic value, but further studies are needed to fully understand the function as well as potential clinical and therapeutic implications of ZEB1 expression in cancers. [ABSTRACT FROM AUTHOR]

DNA methylation is a critical epigenetic mechanism involved in key cellular processes. Its deregulation has been linked to many human cancers including esophageal squamous cell carcinoma (ESCC). This study was designed to explore the whole methylation status of ESCC and to identify potential plasma biomarkers for early diagnosis. We used Infinium Methylation 450k array to analyze ESCC tissues (n = 4), paired normal surrounding tissues (n = 4) and normal mucosa from healthy individuals (n = 4), and combined these with gene expression data from the GEO database. One hundred and sixty eight genes had differentially methylated CpG sites in their promoter region and a gene expression pattern inverse to the direction of change in DNA methylation. These genes were involved in several cancer-related pathways. Three genes were validated in additional 42 ESCC tissues and paired normal surrounding tissues. The methylation frequency of EPB41L3, GPX3, and COL14A1 were higher in tumor tissues than in normal surrounding tissues (P<0.017). The higher methylation frequency of EPB41l3 was correlated with large tumor size (P = 0.044) and advanced pT tumor stage (P = 0.001). The higher methylation frequency of GPX3 and COL14A1 were correlated with advanced pN tumor stage (P = 0.001 and P<0.001). The methylation of EPB41L3, GPX3, and COL14A1 genes were only found in ESCC patients' plasma, but not in normal individuals upon testing 42 ESCC patients and 50 healthy individuals. Diagnostic sensitivity was increased when methylation of any of the 3 genes were counted (64.3% sensitivity and 100% specificity). These differentially methylated genes in plasma may be used as biomarkers for early diagnosis of ESCC. [ABSTRACT FROM AUTHOR]

Aims To investigate the aberrant expression of CD117 in oesophageal squamous cell carcinoma ( SCC) and its prognostic significance. Methods and results Immunohistochemical staining for CD117 was performed on tissue microarray and routine tissue sections from 157 oesophageal SCC patients and 10 normal oesophageal epithelia adjacent to tumour. The positive rate of CD117 expression was 29.9% in oesophageal SCC tissues, whereas no CD117 expression was detected in the 10 normal oesophageal epithelia. CD117 expression was significantly associated with T stage ( P < 0.001), distant metastasis ( P = 0.015), lymph node metastasis ( P = 0.019), and clinical stage ( P = 0.021). Progression-free survival in the patients with CD117-positive tumours was shorter than that in the patients with CD117-negative tumours ( P = 0.010). In univariate analyses, CD117 expression was the most significant factor for overall survival of oesophageal SCC patients ( P < 0.001), followed by lymph node metastasis ( P = 0.001), T stage ( P = 0.002), clinical stage ( P = 0.006), distant metastasis ( P = 0.020), and histological grade ( P = 0.027). Multivariate analyses verified that CD117 expression was an independent prognostic marker for oesophageal SCC patients ( P = 0.002). In addition, CD117 expression predicted poorer survival in patients without distant metastases. Conclusions CD117 expression in operable oesophageal SCC may be a valuable prognostic marker, and detection of its expression in clinical samples may be useful in defining a subclass of oesophageal SCCs with extremely poor clinical outcome, which may require a specially targeted treatment modality. [ABSTRACT FROM AUTHOR]

Notch signaling involves the processes that govern cell proliferation, cell fate decision, cell differentiation and stem cell maintenance. Due to its fundamental role in stem cells, it has been speculated during the recent years that Notch family may have critical functions in cancer stem cells or cancer cells with a stem cell phenotype, therefore playing an important role in the process of oncogenesis. In this study, expression of Notch family in KYSE70, KYSE140 and KYSE450 squamous esophageal cancer cell lines and virus transformed squamous esophageal epithelial cell line Het-1A was examined by quantitative RT-PCR. Compared to the Het-1A cells, higher levels of Nocth1 and Notch3 expression in the cancer cell lines were identified. Due to the finding that NOTCH3 mainly mediates squamous cell differentiation, NOTCH1 expression was further studied in these cell lines. By Western blot analyses, the KYSE70 cell line which derived from a poorly differentiated tumor highly expressed Notch1, and the Notch1 expression in this cell line was hypoxia inducible, while the KYSE450 cell line which derived from a well differentiated tumor was always negative for Notch1, even in hypoxia. Additional studies demonstrated that the KYSE70 cell line was more 5-FU resistant than the KYSE450 cell line and such 5-FU resistance is correlated to Notch1 expression verified by Notch1 knockdown experiments. In clinical samples, Notch1 protein expression was detected in the basal cells of human esophagus epithelia, and its expression in squamous cell carcinomas was significantly associated with higher pathological grade and shorter overall survival. We conclude that Notch1 expression is associated with cell aggressiveness and 5-FU drug resistance in human esophageal squamous cell carcinoma cell lines in vitro and is significantly associated with a poor survival in human esophageal squamous cell carcinomas. [ABSTRACT FROM AUTHOR]

To investigate the value of spleen and pancreatic tail thorax translocation on the residual stomach esophagus anastomosis. 10 patients with esophageal carcinoma after gastrectomy were enrolled in this study. Lesions were removed through left thoracotomy and residual stomach was fully mobilized, with short gastric artery being reserved. Spleen and pancreatic tail were dissected from the back of peritoneum and transposed into thorax. Residual stomach esophagus anastomosis was performed. All the operation went favorably. Patients were recovered rapidly and a relatively good prognosis was acquired. Late leakage and pleural effusion happened in one case respectively, but these complications were cured through conservative management without operation death. Residual stomach is an ideal candidate for the replacement of esophagus and residual stomach esophagus anastomosis is a simple operative alternative with few trauma and good results for the treatment of esophageal carcinoma after gastrectomy. [ABSTRACT FROM AUTHOR]

Background: Surgery is the gold standard treatment for local advanced disease, while definitive concurrent chemoradiotherapy (DCRT) is recommended for those who are medically unable to tolerate major surgery or medically fit patients who decline surgery. The primary aim of this trial is to compare the outcomes in Chinese patients with oesophageal squamous cell cancer with locally advanced resectable disease who have received either surgery or DCRT.Methods/design: One hundred ninety-six patients with T1bN + M0 or T2-4aN0-2 M0 oesophageal squamous cell cancer will be randomised to the DCRT group or the surgery group. In the DCRT group, patients will be given intensity-modulated radiation therapy (IMRT) with 50 Gy/25 fractions and basic chemotherapy with 5-fluorouracil regimens. In the surgery group, patients will receive neoadjuvant chemoradiotherapy (NCRT) and standard oesophagectomy. Five years of follow-up will be scheduled for patients. The primary endpoints are 2-year/5-year overall survival; the secondary endpoints are 2-year/5-year progression-free survival, treatment-related adverse events and the patients' quality of life. The main evaluation methods include oesophagoscopy, endoscopic ultrasonography and biopsy, oesophageal barium meal, computed tomography, positron emission tomography-computed tomography, blood tests and questionnaires.Discussion: The preponderant oesophageal cancer pathology type is dramatically different in western Caucasian and Asian oesophageal cancer patients: Caucasian patients present with 80% adenocarcinomas, and Asians patients present with 95% squamous cell carcinomas. This phenomenon needs more in-depth studies to elucidate the differences in these populations. Based on the results of this study, we will show whether DCRT will benefit patients more than oesophagectomy. This study will contribute more evidence to the management of oesophageal squamous cell cancer.Trial Registration: ClinicalTrials.gov, NCT02972372 . Registered on 26 November 2016. [ABSTRACT FROM AUTHOR]

Background: The role of TMEM176A in human hepatocellular carcinoma (HCC) is unknown. This study explored the epigenetic regulation and function of TMEM176A in human HCC. Materials and methods: Twelve HCC cell lines and 126 cases of primary cancer were analyzed. Methylation-specific PCR, immunohistochemistry, flow cytometry, and xenograft mouse models were employed. Results: TMEM176A was highly expressed in SNU387, SNU182, Huh1, and SNU475 cells; reduced expression was observed in HepG2 and PLC/PRF/5 cells; and no expression was found in SNU449, HBXF344, SMMC7721, Huh7, and LM3 cells. Unmethylation of the TMEM176A promoter was detected in SNU387, SNU182, Huh1, and SNU475 cells; partial methylation was observed in HepG2 and PLC/PRF/5 cells; and complete methylation was found in SNU449, HBXF344, SMMC7721, Huh7, and LM3 cells. Upon treatment with 5-Aza-2-deoxycytidine, re-expression of TMEM176A was detected in SNU449, HBXF344, SMMC7721, Huh7, and LM3 cells; increased expression of TMEM176A was observed in HepG2 and PLC/PRF/5 cells; and no expression changes were found in SNU387, SNU182, Huh1, and SNU475 cells. The TMEM176A promoter region was methylated in 75.4% (95/126) of primary human HCC. Reduced expression of TMEM176A was associated with promoter region methylation (P < 0.05). No association was found between TMEM176A promoter methylation and age, gender, HBV infection, liver cirrhosis, tumor size, lymph node metastasis, vessel cancerous embolus, number of lesions, and TNM stage (all P > 0.05). These results demonstrated that the expression of TMEM176A is regulated by promoter region methylation. Methylation of the TMEM176A promoter was significantly associated with tumor cell differentiation (P < 0.05) and was an independent prognostic factor for poor 3-year overall survival (OS, P < 0.05). TMEM176A expression induced cell apoptosis; inhibited cell proliferation, migration, and invasion; suppressed human HCC cell xenograft growth in mice; and inhibited ERK signaling in HCC cells. Conclusion: The promoter region of TMEM176A is frequently methylated in human HCC, and the expression of TMEM176A is regulated by promoter region methylation. Methylation of the TMEM176A promoter may serve as a diagnostic and prognostic marker in HCC. TMEM176A suppresses HCC growth by inhibiting the ERK signaling pathway. [ABSTRACT FROM AUTHOR]

After publication of the original article [1], it came to the authors’ attention that a reference was omitted from the Background. [ABSTRACT FROM AUTHOR]

58 years old male patient underwent esophagectomy for esophageal cancer. Refractory chylothorax happened after operation in spite of different treatment including conservation therapy and thoracic duct ligation. He was enterally administrated 250 mL 30% intralipid before operation. Exploration showed there was a milky leakage from the soft tissue near the anastomotic stoma behind aortic arch where is difficult to handle. We gently mobilized the aorta in the front of the ninth spine and bundled it with its adjacent tissue including azygos vein and thoracic duct with a dacron patch. The leakage ceased rightly and the following recovery went smoothly. [ABSTRACT FROM AUTHOR]