BACKGROUND: Esophageal cancer (EC) possesses a high degree of malignancy and exhibits poor therapeutic outcomes and prognosis. However, its pathogenesis remains unclear. With the development of macrogene sequencing technology, changes in the intestinal flora have been found to be highly related to the development of EC, although discrepancies and controversies remain in this research area.
METHODS: We comprehensively searched the PubMed, EMBASE, and Cochrane\'s Central Controlled Trials Register and the Scientific Network\'s database search projects based on systematically reviewed preferred reporting projects and meta-analyses. We used Engauge Digitizer for data extraction and Stata 15.1 for data analysis. In addition, we used the Newcastle-Ottawa Scale for grade grading and forest and funnel plots, sensitivity, and Egger and Beggar tests to evaluate the risk of bias.
RESULTS: This study included 10 studies that assessed stool, tumor, and nontumor esophageal mucosa (gastroscopy and surgical resection) samples from 527 individuals, including 273 patients with EC and 254 healthy control group. We observed remarkable differences in microbial diversity in EC patients compared to healthy controls. The Chao1 index (46.01 vs. 42.67) was significantly increased in EC patients, whereas the Shannon index (14.90 vs. 19.05), ACE (39.24 vs. 58.47), and OTUs(28.93 vs. 70.10) were significantly lower. At the phylum level, the abundance of Bacteroidetes (37.89 vs. 32.77) increased significantly, whereas that of Firmicutes (37.63 vs. 38.72) decreased significantly; the abundance of Clostridium and Verruciformis increased, while that of Actinobacteria and Proteobacteria decreased to varying degrees. The abundance of Bacteroides (8.60 vs. 15.10) and Streptococcaceae (15.08 vs. 27.05) significantly reduced in EC.
CONCLUSIONS: According to our meta-analysis, in patients with EC, the Chao1 index increased, whereas the Shannon and the OTUs decreased. At the phylum level, the abundance of Firmicutes decreased significantly, whereas that of Bacteroidetes and Proteobacteria increased significantly. At the genus/family level, the abundance of Bacteroidaceae, Prevotellaceae and Streptococcaceae decreased significantly, whereas that of Veillonellaceae increased. This meta-analysis identified changes in gut microbiota in patients with EC; however, its conclusions were inconsistent.

The role of selenium in the developmental process of esophageal cancer (EC) requires further investigation. To explore the relationship between selenium-related factors and EC through bioinformatic analysis, a case-control study was conducted to verify the results. Utilizing the GEPIA and TCGA databases, we delineated the differential expression of glutathione peroxidase 3 (GPx3) in EC and normal tissues, identified differentially expressed genes (DEGs), and a performed visualization analysis. Additionally, 100 pairs of dietary and plasma samples from esophageal precancerous lesions (EPLs) of esophageal squamous cancer (ESCC) cases and healthy controls from Huai\'an district, Jiangsu, were screened. The levels of dietary selenium, plasma selenium, and related enzymes were analyzed using inductively coupled plasma mass spectrometry (ICP-MS) or ELISA kits. The results showed lower GPx3 expression in tumor tissues compared to normal tissues. Further analysis revealed that DEGs were mainly involved in the fat digestion and absorption pathway, and the core protein fatty acid binding protein 1 (FABP1) was significantly upregulated and negatively correlated with GPx3 expression. Our case-control study found that selenium itself was not associated with EPLs risk. However, both the decreased concentration of GPx3 and the increase in FABP1 were positively correlated with the EPLs risk (p for trend = 0.035 and 0.046, respectively). The different expressions of GPx3 and FABP1 reflect the potential of selenium for preventing ESCC at the EPLs stage. GPx3 may affect myocardial infarction through FABP1, which remains to be further studied.

Esophagus cancer (EC) is one of the most aggressive malignant digestive system tumors and has a high clinical incidence worldwide. Magnolol, a natural compound, has anticancer effects on many cancers, including esophageal carcinoma, but the underlying mechanism has not been fully elucidated. Here, we first find that magnolol inhibits the proliferation of esophageal carcinoma cells and enhances their autophagy activity in a dose- and time-dependent manner. This study demonstrates that magnolol increases the protein levels of LC3 II, accompanied by increased HACE1 protein levels in both esophageal carcinoma cells and xenograft tumors. HACE1-knockout (KO) cell lines are generated, and the ablation of HACE1 eliminates the anti-proliferative and autophagy-inducing effects of magnolol on esophageal carcinoma cells. Additionally, our results show that magnolol primarily promotes HACE1 expression at the transcriptional level. Therefore, this study shows that magnolol primarily exerts its antitumor effect by activating HACE1-OPTN axis-mediated autophagy. It can be considered a promising therapeutic drug for esophageal carcinoma.

Purpose: To gain a deeper understanding of the incidence and survival rates of rare esophageal mixed adenoacanthoma (EAM) and esophageal mixed adeno-squamous carcinoma (EASC) to promote a more comprehensive understanding of these two subtypes. Background: EAM and EASC are rare subtypes of esophageal cancer with limited literature available. Extensive research has been conducted on the clinical and pathological characteristics of gastric and colorectal mixed adenoacanthomas, but there is relatively little literature on esophageal mixed adenoacanthomas. Therefore, this study aims to investigate the incidence and survival rates of these two subtypes in depth. Methods: Patients diagnosed with EAM and EASC between 2000 and 2019 were selected from the SEER database for the study. Joinpoint software was used to calculate the incidence rates of esophageal AM and ASC patients, and differences in cancer overall survival (OS) and cancer-specific survival (CSS) based on Kaplan-Meier curves were compared. Multivariate Cox regression analysis was employed to identify independent prognostic factors for OS and CSS, and a prognostic model was established and validated for accuracy. Results: The study found that the incidence of EAM increased until 2014, followed by a decline, while the incidence of EASC decreased until 2017, followed by an increase. Both of these subtypes were more common in male patients and those over the age of 65. For EAM patients, preoperative chemoradiotherapy was associated with better survival rates, while for EASC patients, preoperative radiotherapy combined with adjuvant chemotherapy improved survival. Finally, we constructed nomograms for predicting the overall survival of EAM and EASC patients by incorporating identified risk factors, which demonstrated good sensitivity and specificity. Conclusion: EAM and EASC are rare subtypes of esophageal cancer, and an in-depth exploration of their incidence and survival rates provides valuable data and insights for understanding these rare esophageal cancer subtypes. This information can assist clinical decision-making for healthcare professionals.

Licochalcone A (LCA) is a flavonoid isolated from Glycyrrhiza uralensis Fisch that has shown promising therapeutic effects in various cancers. This study attempted to analyze its therapeutic potential for esophageal cancer (EC). Combining multiple databases and network pharmacology, we found that the mechanism of LCA inhibiting EC may be closely related to p53 signaling pathway, cell cycle regulation and apoptosis. Molecular docking was then used to predict the affinity between LCA and key targets. Subsequently, we selected three common EC cell lines for in vitro validation. LCA treatment significantly inhibited EC cell proliferation and colony formation. Wound healing and transwell assay showed that LCA can reduce the migration and invasion of EC cells, and down-regulated the expression of matrix metalloproteinases (MMP). LCA promoted excessive ROS production, decreased mitochondrial membrane potential, and upregulated the expression of Bax, Caspase3 and Caspase-9, all of which are involved in apoptosis. LCA treatment blocked the cell cycle in G2/M phase and decreased the expression of cyclin D1, cyclin B1, and CDK1. LCA significantly up-regulated p53 protein and gene expression, thereby inducing apoptosis and cycle arrest. Finally, the xenograft tumor model was established by subcutaneous injection of Eca-109 cells. LCA administration inhibited tumor growth by activating p53 signaling pathways and apoptosis. Meanwhile, there was no significant weight loss and few major organotoxicity and hematotoxicity. In conclusion, LCA is an excellent candidate for EC treatment by regulating p53 pathway to induce G2/M phase arrest and apoptosis.

Esophagus cancer (EC) is a highly malignant and metastatic cancer. Poly(ADP-ribose) glycohydrolase (PARG), a DNA replication and repair regulator, inhibits cancer cell replication defects. This study aimed to explore the role of PARG in EC. The biological behaviors were analyzed using MTT assay, Transwell assay, scratch test, cell adhesion assay, and western blot. PARG expression was detected using quantitative PCR and immunohistochemical assay. The regulation of the Wnt/β-catenin pathway was assessed using western blot. The results showed that PARG was highly expressed in EC tissues and cells. Knockdown of PARG suppressed cell viability, invasion, migration, adhesion, and epithelial-mesenchymal transition. Conversely, overexpression of PARG promoted the biological behaviors mentioned above. Moreover, overexpression of PARG promoted the activation of the Wnt/β-catenin pathway rather than the STAT and Notch pathways. XAV939, the Wnt/β-catenin pathway inhibitor, partly abolished the biological behaviors mediated by PARG overexpression. In conclusion, PARG promoted the malignant advancement of EC via activating the Wnt/β-catenin pathway. These findings suggested that PARG might be a new therapeutic target for EC.

LncRNA PART1 has been confirmed related to multiple cancer bioactivities mediated with vascular endothelial growth factor signaling. Nevertheless, the role of LncRNA PART1 in esophageal cancer induced angiogenesis remains unclear. The present work focused on assessing LncRNA PART1 effects on esophageal cancer-induced angiogenesis and exploring possible mechanisms.
Western blot and immunofluorescence were conducted for identifying EC9706 exosomes. MiR-302a-3p and LncRNA PART1 levels were assessed by real-time quantitative polymerase chain reaction. Cell Counting Kit-8, EdU, wound healing, transwell, and tubule information were adopted for detecting human umbilical vein endothelial cell viability, proliferation, migration, invasion, and tubule information, respectively. Starbase software and dual-luciferase reporter were conducted for predicting and judging the expression interrelation of LncRNA PART1 and its potential target-miR-302a-3p. The same methods were carried out for verifying the inhibiting influences of miR-302a-3p upregulation and its potential target-cell division cycle 25 A.
LncRNA PART1 levels were upregulated and related to the overall survival of patients in esophageal cancer. EC9706-Exos accelerated human umbilical vein endothelial cell proliferation, migration, invasion, and tubule formation via LncRNA PART1. LncRNA PART1 served as a sponge of miR-302a-3p, then miR-302a-3p targeted cell division cycle 25 A, and EC9706-Exos accelerated human umbilical vein endothelial cell angiogenesis via LncRNA PART1/ miR-302a-3p/cell division cycle 25 A axis.
EC9706-Exos accelerates human umbilical vein endothelial cell angiogenesis via LncRNA PART1/miR-302a-3p/ cell division cycle 25 A axis, indicating EC9706-Exos may act as a promoter of angiogenesis. Our research will contribute to clarify the mechanism of tumor angiogenesis.

UNASSIGNED: Epidemiological studies provide limited information on the relationship between dairy consumption and the incidence of esophagus cancer (EC). We examined whether eating dairy foods is associated with a lower risk of EC in an American population.
UNASSIGNED: In our study, we analyzed data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial, which included 101,723 subjects. Dairy product consumption was assessed using a dietary history questionnaire. We used Cox regression and restricted cubic splines to assess whether dairy consumption is associated with EC incidence.
UNASSIGNED: A total of 154 EC cases were identified after a median follow-up of 12.2 years. After adjusting for confounders, we discovered no statistically significant correlation between total dairy product consumption and EC risk (HR with 95% CI for ≥1.79 servings/day vs. ≤0.6 servings/day: 0.83, 0.50-1.38; p for trend = 0.465). Additionally, no associations were found between EC risk and other dairy foods such as milk, yogurt, and cheese.
UNASSIGNED: We concluded that the findings of the PLCO cohort do not suggest dairy consumption reduces the risk of EC.

Numerous epidemiological and laboratory studies on essential trace elements have reported protective associations in developing various cancer types, including esophagus cancer (EC). However, the results are not always consistent. Some essential trace elements could play a vital role in preventing esophagus cancer. Some showed no association with esophageal cancer risk, while others harmed individuals. This article reviews the association between the intake or supplementation of essential trace elements (especially zinc, copper, iron, and selenium) and the risk of esophageal cancer. Generally, zinc intake may decrease the risk of esophageal cancer (EC), especially in high esophageal squamous cell carcinoma (ESCC) prevalence regions. The association between copper supplementation and EC remains uncertain. Total iron consumption is thought to be associated with lower EC risk, while heme iron intake may be associated with higher EC risk. Selenium intake showed a protective effect against EC, especially for those individuals with a low baseline selenium level. This review also prospects the research direction of the association between EC and essential trace elements.

BACKGROUND: Abnormal expression of circular RNAs (circRNAs) plays an important role in tumorigenesis and radiosensitivity of many cancers. Nevertheless, it is not clear whether circ_0001686 is associated with the development and radiosensitivity of esophagus cancer.
METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of circ_0001686, microRNA-876-5p (miR-876-5p) and spindlin 1 (SPIN1). Counting Kit-8 (CCK-8) assay, EdU assay, flow cytometry and transwell assay were applied to evaluate cell viability, cell proliferation, cell apoptosis and cell invasion capacities. Radiosensitivity was monitored by colony formation assay. The target relationship between miR-876-5p and circ_0001686 or SPIN1 was identified by dual-luciferase reporter assay. The protein level of SPIN1 was measured by western blot assay. Xenograft tumor models were used to analyze the influence of circ_0001686 on radiosensitivity and tumor growth in vivo.
RESULTS: The expression levels of circ_0001686 and SPIN1 were increased, while miR-876-5p was decreased in esophagus cancer tissues and cells. Interference of circ_0001686 constrained cell proliferation and invasion, but promoted cell apoptosis and radiosensitivity. Additionally, miR-876-5p was the target of circ_0001686 and miR-876-5p inhibition effectively ameliorated the impacts of circ_0001686 deficiency on tumorigenesis and radiosensitivity. Moreover, SPIN1 was a direct target of miR-876-5p and SPIN1 overexpression partially overturned the effects of miR-876-5p transfection on tumor progression and radiosensitivity. Importantly, circ_0001686 could sponge miR-876-5p to regulate SPIN1 expression. In addition, circ_0001686 silencing also constrained tumor growth and increased radiosensitivity in vivo.
CONCLUSIONS: Circ_0001686 contributed to the progression and radioresistance of esophagus cancer cells via regulating SPIN1 expression by targeting miR-876-5p, providing a new therapeutic target for improving the prognosis of esophagus cancer patients.