Mechanism of METTL14-mediated m6A modification in non-small cell lung cancer cell resistance to cisplatin.

Methyltransferase-like 14 (METTL14) mediates N6-methyladenosine (m6A) modification to influence cancer progression. This study aims to determine the mechanism of METTL14-mediated m6A in non-small cell lung cancer (NSCLC) cell resistance to cisplatin (DDP). METTL14, miR-19a-5p, RBM24, and AXIN1 expressions in NSCLC tissues/cells were determined. DDP-resistant cell line was obtained, followed by the interference of METTL14 expression. NSCLC cells were treated with DDP to establish a drug-resistant cell line, and METTL14 expression in cells was intervened. The IC50 of NSCLC cells to DDP was measured by CCK-8 assay. NSCLC cell proliferation and apoptosis were observed by clone formation assay and flow cytometry. The content of m6A in total RNA in tissues and cells of NSCLC patients was detected using m6A Methylation Quantification Kit. The expressions of DGCR8-bound pri-miR-19a and m6A-modified pri-miR-19a were detected. The binding relationships between miR-19a-5p and RBM24 and RBM24 and AXIN1 were validated using dual-luciferase assay and RNA immunoprecipitation. Finally, mouse xenograft tumor model was established to verify the role of METTL14 in vivo. METTL14 was highly expressed in NSCLC. METTL14 silencing diminished IC50 to DDP, repressed NSCLC cell proliferation, and enhanced apoptosis. METTL14-mediated m6A induced recognition and processing of pri-miR-19a by DGCR8, thus promoting the transition of pri-miR-19a to miR-19a-5p, repressing RBM24 expression, reducing the binding of RBM24 and AXIN1, and suppressing AXIN1 transcription. miR-19a-5p overexpression or RBM24/AXIN1 silencing abolished the effect of METTL14 silencing on NSCLC cell resistance to DDP. METTL14 silencing in vivo enhanced the suppressive role of DDP to tumor growth. Collectively, METTL14-mediated m6A modification facilitated NSCLC cell resistance to DDP via miR-19a-5p/RBM24/AXIN1 axis. KEY MESSAGES: • METTL14 is highly expressed NSCLC and further increased in DDP-resistant cells. • METTL14 silencing attenuates DDP resistance of NSCLC cells. • METTL14 promotes the nature of pri-miR-19a by upregulating pri-miR-19a m6A level. • miR-19a-5p targets RBM24, thus reducing the binding of RBM24 and AXIN1 and inhibiting AXIN1 transcription. • METTL14 silencing in vivo enhances the suppressive role of DDP to tumor growth.

NADPH Oxidase 4: A Potential Therapeutic Target of Malignancy.

Reactive oxygen species (ROS) play a crucial role in the regulation of tumor occurrence and development. As a main source of ROS, NADPH oxidases are key enzymes that mediate electron transport within intracellular membranes. Of the NOX members that have been reported to be dysregulated in a wide variety of tumors, NOX4 is the member to be most frequently expressed. Numerous studies have elucidated that NOX4 gets involved in the regulation of tumor proliferation, metastasis, therapy resistance, tumor-stromal interaction and dysregulated tumor metabolism. In this review, we primarily discussed the biological function of NOX4 in tumorigenesis and progression of multiple cancer models, including its role in activating oncogenic signaling pathways, rewiring the metabolic phenotype and mediating immune response. Besides, the development of NOX4 inhibitors has also been unraveled. Herein, we discussed the interplay between NOX4 and tumorigenesis, proposing NOX4 as a promising therapeutic target waiting for further exploration.

Restored microRNA-519a enhances the radiosensitivity of non-small cell lung cancer via suppressing EphA2.

Accumulating evidence has demonstrated that microRNA-519a (miR-519a) acts as the tumor suppressor in various cancers, but little is known regarding its intrinsic regulatory mechanisms in non-small cell lung cancer (NSCLC). Here, we aimed to investigate the role of miR-519a-targeted ephrinA2 receptor (EphA2) in radiosensitivity of NSCLC. MiR-519a and EphA2 expression in NSCLC and paracancerous tissues were detected using RT-qPCR and western blot analysis. A549 cell line was cultured and radiation-resistant cell line A549R was constructed using fractionated X-ray irradiation of these cells at 60 Gy. Colony formation ability and radioresistance of parent strain A549 and resistant strain A549R were detected with restored miR-519a and depleted EphA2. MTT assay was used to measure cell proliferation, flow cytometry was performed for determination of cell cycle distribution and apoptosis. The migration and invasion abilities were assessed by Transwell assay. The target relationship between miR-519a and EphA2 was verified. Results suggested that miR-519a was downregulated and EphA2 was upregulated in NSCLC tissues and cells, and miR-519a targeted EphA2. MiR-519a expression declined, while EphA2 expression elevated in A549R cells versus A549 cells. Upregulated miR-519a and downregulated EphA2 suppressed D0, Dq, survival fraction (SF2) and N-value, arrested cells at G0/G1 phase, advanced the apoptosis and attenuated migration, proliferation, and invasion of A549 and A549R cells. Overexpression of EphA2 reversed the promotion of upregulated miR-519a on radiosensitivity of NSCLC cells. Our results revealed that miR-519a enhances radiosensitivity of NSCLC by inhibiting EphA2 expression. Moreover, miR-519a serves as a target for NSCLC treatment.

Efficacy and safety of endoscopic full-thickness resection in the colon and rectum using an over-the-scope device: a meta-analysis.

OBJECTIVE: Relevant publications were identified by searching PubMed, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science before December 1, 2019. Studies in which ≥ 10 cases of colorectal lesions were resected with endoscopic full-thickness resection (EFTR) were included. Rates of efficacy (technical success (en bloc), full-thickness resection and R0 resection), rates of safety (bleeding, perforation and postpolypectomy syndrome) and rates of follow-up (residual/recurrent adenoma, fate of over-the-scope clip and surgery for any reason) were pooled and analyzed. Forest plots were graphed based on random effects models. Subgroup analyses and sensitivity analyses were also performed if significant heterogeneity existed. RESULTS: A total of 469 patients across 9 studies were eligible for analysis. The pooled rates of technical success, full-thickness resection and R0 resection were 94.0% (95% CI 89.8-97.3%), 89.5% (83.9-94.2%) and 84.9% (75.1-92.8%), respectively. The pooled estimates of bleeding, perforation and postpolypectomy syndrome were 2.2% (95% CI 0.4-4.9%), 0.19% (95% CI 0.00-1.25%) and 2.3% (95% CI 0.1-6.3%), respectively. Finally, the pooled rates of residual/recurrent adenoma, fate of OTSC and surgery for any reason were 8.5% (95% CI 4.1-14.0%), 80.3% (95% CI 67.5-90.8%) and 6.3% (2.4-11.7%), respectively. CONCLUSIONS: EFTR for nonlifting, invasive lesions in the colon and rectum appears to be effective and safe. However, future studies are necessary to explore the role of EFTR in large colorectal lesions and specify its indications.

Effect of dynamic position changes during colonoscope withdrawal: a meta-analysis of randomized controlled trials.

BACKGROUND: Colonoscopies are considered to be the primary screening test and gold standard test for colorectal cancer. Position changes during colonoscope withdrawal are believed to be associated with an increased adenoma detection rate (ADR) and polyp detection rate (PDR). However, previous results conflicted, and this study aimed to elucidate the effectiveness of dynamic position changes during colonoscope withdrawal. METHODS: The relevant publications were identified by searching the medical databases. The primary outcomes were the ADR and PDR, which were pooled and analyzed. The secondary outcome was the withdrawal time. The studies that supplied the ADR and PDR for different segments of the colon were separated into subgroup analyses. RESULTS: Five randomized controlled trials were eligible for analysis. The total ADR was higher with dynamic position changes than with a static position (odds ratio, [OR] 1.34; 95% confidence interval [CI] 1.13-1.59; p < 0.001), with low evidence of between-study heterogeneity (I2 = 0%). Although the total PDR was slightly higher with dynamic position changes than with a static position (OR 1.23; 95% CI 0.88-1.73), there difference was not statistically significant (p = 0.22). The withdrawal time was only increased by 0.47 min (95% CI - 0.11 to 1.06) with dynamic position changes, without statistical significance (p = 0.11). The subgroup analysis showed that the ADR and PDR for the transverse colon were higher with dynamic position changes, with pooled estimates of ADR (OR 1.72; 95% CI 1.02-2.88; p = 0.04) and PDR (OR 1.79; 95% CI 1.08-2.96; p = 0.02). CONCLUSION: Dynamic position changes during colonoscope withdrawal increased the total ADR; however, no obvious increase was found in the total PDR. The withdrawal time was not significantly prolonged with dynamic position changes. Subgroup analysis showed that the ADR and PDR in the transverse colon were obviously improved with dynamic position changes.

Underwater endoscopic mucosal resection for colorectal lesions: a meta-analysis.

BACKGROUND: Underwater endoscopic mucosal resection (UEMR) of colorectal lesions is emerging as an alternative method to conventional endoscopic mucosal resection (CEMR). This study aimed to evaluate the feasibility and safety of UEMR for colorectal lesions. METHODS: The PubMed, Embase, Cochrane and Web of Science databases were searched before May 10, 2020. The primary outcomes were en bloc resection rate (feasibility) and adverse event rate (safety). The secondary outcome was recurrence and residual adenoma rate. If there was a comparison between UEMR and CEMR, data about en bloc resection, delayed bleeding, and recurrence and residual adenoma were extracted and compared. The pooling of the effect size was conducted using random-effects models, and the Q-statistic, τ2, and I2 were used to evaluate heterogeneity. RESULTS: Seventeen studies (759 patients, 893 lesions) were included. The pooled estimate for the en bloc resection rate was 59% (95% CI 43-75%) with significant heterogeneity (I2 = 97%). Due to the heterogeneity, it is not suitable to conduct pooled estimates analysis, so the en bloc resection rate was from 10 to 89%. The pooled estimate for delayed bleeding was 2% (95% CI, 1%-3%) and only two cases had perforation. The pooled rate of recurrence and residual adenoma was 5% (95% CI 2%-8%). Compared with CEMR, UEMR could achieve a higher en bloc resection rate (OR 1.61; 95% CI 1.02-2.53; p = 0.04) with a lower rate of recurrence and residual adenoma (OR 0.18; 95% CI 0.07-0.46; p < 0.01). CONCLUSIONS: UEMR for colorectal lesions was capable of a high en bloc resection rate, low adverse event rate and low recurrence. UEMR may be considered an effective and safe alternative for treating colorectal lesions.

Gastric per-Oral Endoscopic Myotomy for Refractory Gastroparesis: A Meta-Analysis.

BACKGROUND: The emerging gastric per-oral endoscopic myotomy (G-POEM) is becoming an alternative treatment method for gastroparesis. This study aimed to evaluate the feasibility and safety of G-POEM for gastroparesis. METHODS: Relevant publications were identified through searching PubMed, EMBASE, Cochrane Library, and Web of Science before April 1, 2019. Studies presenting the clinical data of G-POEM for the treatment of gastroparesis were included. Data about effectiveness and safety were extracted, pooled, and analyzed. Forest plots were graphed based on random effects models. RESULTS: A total of 272 patients representing 8 studies were eligible for analysis. The pooled rates of GCSI at preprocedure, 1-3 months, 6 months, and 12 months, were 3.25 (95% CI, 2.75-3.75), 1.80 (95% CI, 1.10-2.49), 1.56 (95% CI, 0.45-2.68), and 1.10 (95% CI, 0.75-1.45), respectively. The pooled results of 4-h GES pre- and post-G-POEM were 41.89% (95% CI, 32.75-51.03%) and 16.48% (95% CI, 9.83-23.14%), respectively. Furthermore, the pooled clinical response rate was 84% (95% CI, 77-89%). The GES improvement rate and GES normal rate were also analyzed, and the results were 84% (95% CI, 77-90%) and 53% (95% CI, 39-66%), respectively. Finally, the pooled adverse events rate was 12% (95% CI, 6-19%). CONCLUSIONS: G-POEM was shown to be feasible and safe for the treatment of gastroparesis with various etiologies, which could be a potential first-line therapy for certain patients. Future studies are needed to investigate the appropriate patients for G-POEM to explore the "most beneficial" subgroup of patients.

Layer-by-layer pH-sensitive nanoparticles for drug delivery and controlled release with improved therapeutic efficacy in vivo.

In this work, a pH-sensitive liposome-polymer nanoparticle (NP) composed of lipid, hyaluronic acid (HA) and poly(ß-amino ester) (PBAE) was prepared using layer-by-layer (LbL) method for doxorubicin (DOX) targeted delivery and controlled release to enhance the cancer treatment efficacy. The NP with pH-sensitivity and targeting effect was successfully prepared by validation of charge reversal and increase of hydrodynamic diameter after each deposition of functional layer. We further showed the DOX-loaded NP had higher drug loading capacity, suitable particle size, spherical morphology, good uniformity, and high serum stability for drug delivery. We confirmed that the drug release profile was triggered by low pH with sustained release manner in vitro. Confocal microscopy research demonstrated that the NP was able to effectively target and deliver DOX into human non-small cell lung carcinoma (A549) cells in comparison to free DOX. Moreover, the blank NP showed negligible cytotoxicity, and the DOX-loaded NP could efficiently induce the apoptosis of A549 cells as well as free DOX. Notably, in vivo experiment results showed that the DOX-loaded NPs effectively inhibited the growth of tumor, enhanced the survival of tumor-bearing mice and improved the therapeutic efficacy with reduced side-effect comparing with free drug. Therefore, the NP could be a potential intelligent anticancer drug delivery carrier for cancer chemotherapy, and the LbL method might be a useful strategy to prepare multi-functional platform for drug delivery.

Endoscopic submucosal tunnel dissection for superficial esophageal neoplastic lesions: a meta-analysis.

BACKGROUND AND AIMS: The emerging endoscopic submucosal tunnel dissection (ESTD) is becoming an alternative method for superficial esophageal neoplastic lesions. This study aimed to evaluate the effectiveness and feasibility of ESTD for superficial esophageal neoplastic lesions. METHODS: A comprehensive literature review was conducted to search relevant studies through PubMed, EMBASE, Cochrane Library, and Web of Science before 1 December 2018. Studies relating to ESTD for superficial esophageal neoplastic lesions were included. Rates of effectiveness (en bloc resection rate, R0 resection rate, and curative resection rate), rates of feasibility (muscular damage rate, perforation rate, postprocedural bleeding rate, and emphysema rate), and rates of follow-up (recurrence rate and stricture rate) were pooled and analyzed. Forest plots were constructed based on the random-effects model. Sensitivity analyses were also performed if significant heterogeneity existed. RESULTS: Six studies including 414 patients and 436 superficial esophageal neoplastic lesions that underwent ESTD were available for analysis. The pooled estimates of en bloc resection rate, R0 resection rate, and curative resection rate were 98% (95% CI 95.8-99.0%), 87.0% (95% CI 78.2-92.5%), and 87.6% (95% CI 67.4-96.0%), respectively. The pooled outcomes of muscular damage rate, perforation rate, postprocedural bleeding rate and emphysema rate were 19.1% (95% CI 9.8-33.8%), 2.2% (95% CI 1.1-4.1%), 1.6% (95% CI 0.7-3.5%), and 12.2% (95% CI 4.3-29.9%), respectively. Finally, the pooled results of recurrence and stricture were 4.7% (0.9-20.5%) and 20.9% (11.3-35.2%), respectively. CONCLUSIONS: ESTD appears to be an effective and feasible approach for treating superficial esophageal neoplastic lesions. However, future research is needed for new and comprehensive methods to decrease the stricture rate after ESTD.

Efficacy and safety of endoscopic sleeve gastroplasty for obesity patients: a meta-analysis.

BACKGROUND: Endoscopic sleeve gastroplasty (ESG) is a minimally invasive, effective, and safe technique for weight loss intervention. Since a relatively small number of cases were present in previous studies, this study aimed to elucidate the efficacy and safety of ESG. METHODS: Relevant publications were identified through searching PubMed, EMBASE, Cochrane, and Web of Science before March 1, 2019. The percentage of total body weight loss (%TBWL), percentage of excess weight loss (%EWL), and the adverse event rate in each follow-up session were extracted, pooled, and analyzed. Forest plots were graphed based on random effects models. RESULTS: A total of 1542 patients from nine studies were eligible for analysis. The pooled results of %TBWL at 1, 3, 6, and 12 months were 8.78% (p = 0.000), 11.85% (p = 0.000), 14.47% (p = 0.024), and 16.09% (p = 0.063), respectively. The pooled results of %EWL at 1, 3, 6, and 12 months were 31.16% (p = 0.000), 43.61% (p = 0.000), 53.14% (p = 0.000), and 59.08% (p = 0.015), respectively. Finally, the pooled rate of mild adverse events was 72% (p < 0.01), and the pooled estimate of severe adverse events was only 1% (p = 0.08). CONCLUSION: Although the conventional surgical sleeve gastrectomy is the gold standard for bariatric surgery, ESG could be a promising minimally invasive alternative for treating obesity with satisfactory efficacy and low risk.

RUFY3 Predicts Poor Prognosis and Promotes Metastasis through Epithelial-mesenchymal Transition in Lung Adenocarcinoma.

Background: RUFY3 (RUN and FYVE domain-containing protein 3) has been shown to participate in cell migration, membrane transportation, and cellular signaling and is dysregulated in several cancer processes. However, the role of RUFY3 in lung cancer remains unclear. In the present study, we aimed to study the expression of RUFY3 and assess its clinical significance in lung adenocarcinoma. Materials and Methods: We used immunohistochemistry to detect RUFY3 protein expression in human lung adenocarcinoma and adjacent normal lung tissue from 125 patients who underwent surgical resection of the lung cancer. RUFY3 expression was assessed in association with clinicopathological characteristics and clinical prognosis of lung adenocarcinoma patients. The expression of RUFY3 in three different lung adenocarcinoma cell lines and one normal lung epithelial cell (BEAS-2B) was detected by western blot. RNAi technique was used to silence RUFY3. We assessed cell migration by Trans-well assay and wound healing assay. Results: In lung adenocarcinoma tissues, RUFY3 protein was significantly upregulated compared to paired normal lung tissues. High cytoplasmic RUFY3 levels were associated with lymph node metastasis, TNM staging, and survival status. Patients with the highest expression level of RUFY3 had a shorter survival time than patients with the lowest expression. Inhibition of RUFY3 by siRNA inhibited cell migration. Furthermore, silence of RUFY3 lead to up-regulation of E-cadherin, but down-regulation of N-cadherin, Vimentin and Slug. Conclusions: Our study is first to demonstrated that abnormal expression of RUFY3 indicates poor prognosis in lung adenocarcinoma and also indicates that RUFY3 may be related to EMT process. This highlights the potential of RUFY3 as a novel prognostic biomarker for lung adenocarcinoma.

Fabrication Of Dual pH/redox-Responsive Lipid-Polymer Hybrid Nanoparticles For Anticancer Drug Delivery And Controlled Release.

BACKGROUND: The development of biocompatible nanocarriers that can efficiently encapsulate and deliver anticancer drug to the tumor site and provide controlled release of cargos in response to the specific cues for cancer therapy is of great significance. METHODS: In this work, dual pH/redox-responsive fabrication of hybrid lipid-polymer nanoparticles (LPNPs) self-assembled from amphiphilic polymer poly(ethylene glycol) methyl ether-grafted disulfide-poly(ß-amino esters) (PBAE-ss-mPEG) and PEGylated lipid were prepared and used as drug delivery carriers. The optimization of PEGylated lipid modification was confirmed by analysis of particle size, polydispersity index (PDI), cellular uptake, serum stability, and drug loading capacity. The pK b value of LPNPs was determined as 6.55, indicating the pH-sensitivity. The critical micelle concentration (CMC) values and zeta-potential of LPNPs at different pH values were investigated to confirm its pH-sensitivity. The morphology of LPNPs before and after incubation with reducing agent was imaged to study the redox-responsibility. RESULTS: The in vitro results showed that the drug had controlled release from LPNPs triggered by low pH and high concentration of reducing agent. Furthermore, the cytotoxicity of LPNPs was very low, and the doxorubicin (DOX)-loaded LPNPs could efficiently induce the death of tumor cells in comparison to free DOX. CONCLUSION: All results demonstrated that the fabricated LPNPs could be potential anticancer drug delivery carriers with a pH/redox-triggered drug release profile, and PEGylated lipid modification might be a useful method to fabricate the drug delivery platform.

RFC3 induces epithelial­mesenchymal transition in lung adenocarcinoma cells through the Wnt/ß­catenin pathway and possesses prognostic value in lung adenocarcinoma.

Lung cancer is a malignant tumor responsible for the highest mortality rate in humans. The identification of novel functional genes is of great importance in the treatment of lung cancer. The reported roles of replication factor C subunit 3 (RFC3) in tumorigenesis are contradictory. The present study aimed to explore the role and mechanism of RFC3 in lung cancer cells. An immunohistochemical study of 165 lung cancer and adjacent tissues was conducted (123 lung adenocarcinoma tissues and 42 lung squamous cell carcinoma tissues). Kaplan­Meier analysis and Cox multivariate analysis were employed to explore the relationship between RFC3 and patient prognosis. In addition, the proliferation, cell cycle distribution and apoptosis of A549 and H1299 cells were determined by MTT assay and flow cytometry, respectively, following cell transfection to induce overexpression and knockdown of RFC3. A Boyden chamber assay and wound­healing assay were conducted to determine the invasive and migratory abilities of A549 and H1299 cells. Western blotting was used to analyze the effects of RFC3 overexpression and RFC3 small interfering RNA­induced knockdown, and to explore the potential mechanism and pathway underlying the effects of RFC3. Positive expression of RFC3 was detected in lung adenocarcinoma, and overexpression of RFC3 shortened the survival time of patients with lung adenocarcinoma. Furthermore, overexpression of RFC3 increased the invasion and migration of A549 cells, whereas knockdown of RFC3 significantly reduced the invasion and migration of H1299 cells. Ectopic expression of RFC3 induced epithelial­mesenchymal transition (EMT), as determined by downregulation of E­cadherin, and upregulation of N­cadherin, vimentin and Wnt signaling target genes, including c­MYC, Wnt1 and ß­catenin, and the ratio of phosphorylated­glycogen synthase kinase 3 (GSK3)­ß (Ser9)/GSK3­ß. In conclusion, RFC3 may be considered a coactivator that promotes the Wnt/ß­catenin signaling pathway, and induces EMT and metastasis in lung adenocarcinoma.

Paraneoplastic Cushing's syndrome associated with bronchopulmonary carcinoid tumor in youth: A case report and review of the literature.

Paraneoplastic Cushing's syndrome (CushingPS) caused by bronchopulmonary carcinoid tumors presents a diagnostic challenge for clinicians. The present study reports the case of an 18-year-old male patient presenting with rapid weight gain, polyuria, polydipsia and progressive muscle weakness. Chemical and imaging findings suggested ectopic secretion of adrenocorticotropin. Whole-body 18fluorine-fluorodeoxyglucose (18FDG-PET/CT) positron-emission tomography revealed an increased uptake of 18FDG-PET/CT in the right middle lung mass and lobar lymph node. Postoperative pathology confirmed the presence of a typical carcinoid, as well as a lobar lymph node metastasis. The patient underwent a right middle lobectomy with mediastinal lymph node resection, which resulted in symptom clearance, followed by rapid weight loss. No CushingPS or tumor recurrence was observed at the 3-month postoperative follow-up.

Analysis of EHMT1 expression and its correlations with clinical significance in esophageal squamous cell cancer.

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy, requiring effective biomarkers for prognosis and therapeutic responsiveness. Histone H3K9 methyltransferases (EHMT1 and EHMT2) are global genome organizers, which are crucial for maintaining the balance state of cells in a tissue-specific manner. It was previously suggested that EHMT1 expression is a predictor of prognosis in several malignant tumors; however, the prognostic significance of EHMT1 expression in ESCC has not been determined. A cohort of 50 ESCC cases and 46 paired normal esophageal tissue samples were evaluated to assess the levels of EHMT1 expression by immunohistochemistry and reverse transcription-polymerase chain reaction. The SPSS software package was used for statistical data analysis. A significantly upregulated EHMT1 expression was observed in squamous preinvasive lesions and ESCC compared to the matched normal esophageal epithelia (52.0 vs. 21.7%, respectively). The expression of EHMT1 was correlated with tumor grade (G), depth of invasion (T) and lymph node metastasis (N) in ESCC. EHMT1 overexpression was found to be associated with poor cancer-specific survival in squamous cell carcinomas (χ2=3.922, P=0.048). The expression of EHMT1 was identified as an independent prognostic factor for overall survival in ESCC patients. In conclusion, EHMT1 expression is upregulated in ESCC and early preinvasive esophageal squamous lesions and the overexpression of EHMT1 is associated with poor prognosis in ESCC. Therefore, the expression of EHMT1 may be an effective prognostic biomarker for ESCC.