Esophageal Squamous Cell Carcinoma Research Articles

Relationship of Immune-Related Adverse Events with Tumor Response and Prognosis in Esophageal Squamous Cell Carcinoma Following Nivolumab Monotherapy.

Patients across various cancers who develop immune-related adverse events (irAEs) post-immune checkpoint inhibitor (ICI) treatment tend to experience better tumor response and survival than those who do not. However, studies regarding this association in patients with esophageal squamous cell carcinoma (ESCC) are limited. We assessed the relationship of irAEs with tumor response and survival in 82 consecutive patients with unresectable advanced or recurrent ESCC treated with second- or later-line nivolumab, an anti-PD-1 antibody, monotherapy. We observed irAEs in 24 (29.3%) patients, with the overall response and disease control rates in the irAE-positive group being significantly better than those in the irAE-negative group (both p < 0.0001). During the entire period and within 8 weeks of nivolumab initiation, progression-free and overall survivals (PFS and OS, respectively) were significantly better in patients with grade1/2 irAEs than in those without. Univariate and multivariate analyses indicated grade1/2 irAEs during the entire period and within 8 weeks as independent covariates for PFS (entire period: hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.16-0.49, p < 0.001; within 8 weeks: HR 0.46, 95% CI 0.23-0.93, p = 0.03) and OS (entire period: HR 0.24, 95% CI 0.13-0.44, p < 0.001; within 8 weeks: HR 0.41, 95% CI 0.18-0.92, p = 0.03). Grade1/2 irAEs during the entire treatment period and within 8 weeks of nivolumab initiation were significantly associated with improved tumor response and survival in patients with advanced ESCC treated with nivolumab monotherapy. Therefore, mild irAEs may be predictive markers for the response and prognosis of ESCC following ICI treatment.

Dysbiosis of the Upper Gastrointestinal Tract in Head-and-Neck Cancer Survivors: A Pilot Study Using the Capsule Sponge Device

Background: A non-endoscopic capsule-sponge device allows sampling the entire length of the esophagus. Here, we compared microbiomes of the oral cavity, esophagus, and gastric corpus collected by oral swab, capsule-sponge device, and endoscopic biopsy, respectively, in patients representing three distinct risk profiles for esophageal squamous cell carcinoma (ESCC). Methods: The study enrolled 11 patients with esophageal squamous intraepithelial neoplasia, 21 patients after curative treatment for head and neck squamous cell cancer (HNSCC) (HNSCC survivors), and 40 patients with functional dyspeptic (FD) symptoms. Microbial genomic DNA was analyzed using 16S rRNA gene amplicon sequencing. Results: The Shannon index of the capsule-sponge sample microbiota was significantly higher in FD group than in patients after treatment for HNSCC, and the Chao index of gastric samples differed between HNSCC survivors and FD patients. Analysis of the β-diversity of FD patients, HNSCC, and esophageal squamous intraepithelial neoplasia showed that different genera formed at each location. The abundance of 205, 116, and 9 genera differed between FD patients and HNSCC survivors in the gastric, capsule-sponge, and oral samples, respectively; 33 genera differed between the FD group and patients with esophageal squamous intraepithelial neoplasia in capsule-sponge samples. Conclusions: The bacterial communities of the upper digestive tract were clustered according to the anatomic site. Despite substantial differences in gastric and esophageal microbiota samples between FD patients and HNSCC survivors, the microbial members and diversity showed small differences between FD patients and those with esophageal squamous intraepithelial neoplasia. It remains unclear whether gastric and esophageal dysbiosis is associated with or is a consequence of treatment for HNSCC.

A case of esophageal squamous cell carcinoma with epidermization showing a unique morphology.

An 80-year-old woman with a history of endoscopic balloon dilation for esophageal stricture caused by accidental ingestion of caustic soda during infancy presented with dysphagia. Upper gastrointestinal endoscopy revealed a 10-cm-long, highly white, elevated lesion with a feathered appearance. This lesion was determined to be the cause of dysphagia and was completely resected via endoscopic submucosal dissection. Histopathological examination revealed a thick keratin layer on the surface of the stratified squamous epithelium, with a prominent granular layer underneath and some areas showing nuclear atypia. The lesion was diagnosed as a well-differentiated squamous cell carcinoma, pT1a-LPM, derived from epidermoid metaplasia. Cancer genome analysis revealed mutations in TP53 as well as amplification of MYC, FGFR1, chromosome 7, and chromosome 20q. This case suggests that epidermoid metaplasia caused by chronic irritation from an esophageal stricture may have been exacerbated by the dilation procedure.

Prediction of lymphovascular invasion in esophageal squamous cell carcinoma by computed tomography-based radiomics analysis: 2D or 3D ?

BackgroundTo compare the performance between one-slice two-dimensional (2D) and whole-volume three-dimensional (3D) computed tomography (CT)-based radiomics models in the prediction of lymphovascular invasion (LVI) status in esophageal squamous cell carcinoma (ESCC).MethodsTwo hundred twenty-four patients with ESCC (158 LVI-absent and 66 LVI-present) were enrolled in this retrospective study. The enrolled patients were randomly split into the training and testing sets with a 7:3 ratio. The 2D and 3D radiomics features were derived from the primary tumors’ 2D and 3D regions of interest (ROIs) using 1.0 mm thickness contrast-enhanced CT (CECT) images. The 2D and 3D radiomics features were screened using inter-/intra-class correlation coefficient (ICC) analysis, Wilcoxon rank-sum test, Spearman correlation test, and the least absolute shrinkage and selection operator, and the radiomics models were built by multivariate logistic stepwise regression. The performance of 2D and 3D radiomics models was assessed by the area under the receiver operating characteristic (ROC) curve. The actual clinical utility of the 2D and 3D radiomics models was evaluated by decision curve analysis (DCA).ResultsThere were 753 radiomics features from 2D ROIs and 1130 radiomics features from 3D ROIs, and finally, 7 features were retained to construct 2D and 3D radiomics models, respectively. ROC analysis revealed that in both the training and testing sets, the 3D radiomics model exhibited higher AUC values than the 2D radiomics model (0.930 versus 0.852 and 0.897 versus 0.851, respectively). The 3D radiomics model showed higher accuracy than the 2D radiomics model in the training and testing sets (0.899 versus 0.728 and 0.788 versus 0.758, respectively). In addition, the 3D radiomics model has higher specificity and positive predictive value, while the 2D radiomics model has higher sensitivity and negative predictive value. The DCA indicated that the 3D radiomics model provided higher actual clinical utility regarding overall net benefit than the 2D radiomics model.ConclusionsBoth 2D and 3D radiomics features can be employed as potential biomarkers to predict the LVI in ESCC. The performance of the 3D radiomics model is better than that of the 2D radiomics model for the prediction of the LVI in ESCC.

Prediction of Pathologic Complete Response in Esophageal Squamous Cell Carcinoma Using Preoperative Serum Small Ribonucleic Acid Obtained After Neoadjuvant Chemoradiotherapy.

The authors hypothesized that small ribonucleic acid (sRNA) obtained from blood samples after neoadjuvant therapy from patients treated with neoadjuvant chemoradiation therapy (NACRT) could serve as a novel biomarker for predicting pathologic complete response (pCR). This study included 99 patients treated with esophagectomy after NACRT between March 2010 and October 2021 whose blood samples were collected between the end of NACRT and surgery. Next-generation sequencing (NGS) was used to analyze sRNAs from the blood samples. A predictive model for pCR comprising micro-RNA isoforms (isomiR), transfer RNA (tRNA)-derived sRNAs (tsRNAs), and clinical factors was constructed using cross-validation. Of the 99 patients, pCR was diagnosed for 30 and non-pCR for 69 of the patients. Among sRNAs, the isomiRs of let-7b and miR-93 and the tsRNA group derived from tRNA-Gly-CCC/GCC were identified as predictive factors. The clinical factors included a decrease in the maximum standardized uptake value (SUVmax) at the primary site, clinical complete response post-NACRT, preoperative biopsy, and post-NACRT carcinoembryonic antigen levels. The combined predictive model for pCR (C-PM) was established using the three sRNAs and four clinical factors. The area under the curve for the C-PM was 0.84, which was a significant factor in the multivariate analysis (odds ratio, 89.41; 95 % confidence interval 8.1-987.5; p < 0.001). Pathologic complete response after NACRT can be predicted by a predictive model constructed from preoperative clinical factors obtained via minimally invasive procedures and sRNA identified by NGS. Preoperative pCR prediction may influence treatment decision-making after NACRT.

Oxymatrine inhibits migration and invasion of esophageal squamous cell carcinoma cell lines via the MEK1/ERK/β-catenin pathway

Esophageal, cancer is a prevalent malignant tumour of the digestive system in China, and esophageal squamous cell carcinoma (ESCC) accounts for 90 % of all esophageal cancer cases. Currently, the primary treatment involves surgical resection combined with postoperative radiotherapy. In this study, we used two ESCC cell lines to determine whether oxymatrine (OMT) inhibits ESCC, whether the mechanism involves the MEK1/ERK/β-catenin pathway, and how OMT modulates this pathway to affect the development of ESCC. The effects of OMT treatment were monitored with Cell Counting Kit-8 (CCK-8) assays as well as with clony formation, migration and invasion, wound healing, Hoechst 33258, and Western blot analyses. The relationship between OMT and the target was also evaluated by molecular docking and cell stability experiments. These findings suggest that ESCC development and metastasis may be inhibited by OMT and that OMT targets MEK1 through the ERK/β-catenin/EMT pathway to suppress ESCC cell migration and invasion. In addition, in vivo studies confirmed that OMT can inhibit the growth of ESCC cell lines in NOG mice without causing damage to other organs. In conclusion, in vitro experiments, revealed that OMT prevents the migration and invasiveness of ESCC cells by inhibiting the ERK/β-catenin/EMT pathway and thus targeting MAP2K1 (MEK1) in ESCC.

A Case of Esophageal Squamous Cell Carcinoma Detected After Peroral Endoscopic Myotomy in a Patient With Achalasia

A Case of Esophageal Squamous Cell Carcinoma Detected After Peroral Endoscopic Myotomy in a Patient With Achalasia

Nivolumab plus anlotinib hydrochloride in advanced gastric adenocarcinoma and esophageal squamous cell carcinoma: the phase II OASIS trial

Vascular endothelial growth factor inhibitors, including tyrosine kinase inhibitors (TKIs), possess immunomodulatory properties and have shown promising outcomes when combined with anti-PD-1 antibodies. The OASIS phase II trial (NCT04503967) is designed to determine the clinical activity and safety of nivolumab (anti-PD-1) and anlotinib hydrochloride (a multi-targets TKI) as second-line or above therapy in patients with advanced gastric adenocarcinoma (GAC) and esophageal squamous cell carcinoma (ESCC). From December 2020 to September 2022, 45 patients with GAC and 3 with ESCC were enrolled in this study. The pre-specified endpoints were reached, with the primary endpoint of overall response rate achieving 29.2%. For secondary objectives, disease control rate was 64.6%; median progression-free survival was 4.0 months; and median overall survival was 11.1 months with a manageable toxicity profile. The exploratory analyses unveiled that the balance of gut bacteria and the presence of a pre-existing immune signature characterized by a high percentage of CD68+PD-L1+ PD-1+ macrophages and low pretreatment variant allele frequencies (VAF), as well as low expression of certain cytokines were significantly associated with improved clinical outcomes in patients with GAC.

Leiomyomas of the Gastrointestinal Tract: A Clinicopathologic Review

Abstract Introduction/Objective Leiomyomas are benign smooth muscle tumors that can be found anywhere along the gastrointestinal tract (GIT). We undertook a retrospective study to investigate the incidence of GIT leiomyomas and to gain better understanding of their clinicopathologic characteristics. Methods/Case Report The surgical pathology files at our institution were searched for GIT leiomyomas encountered between 07/1994 and 12/2023. The clinical and histopathological findings were recorded. Results (if a Case Study enter NA) 74 leiomyomas were identified in various GIT locations, including esophagus (8), stomach (20), duodenum (3), colon (37) and rectum (6). There were 40 females and 34 males, with an average age of 61.5 years. Esophageal leiomyomas showed a mean size of 2.2 cm. 5/8 patients had synchronous adenocarcinomas of gastroesophageal junction and 1/8 patient had synchronous squamous cell carcinoma of esophagus. Gastric leiomyomas showed a mean size of 2.0 cm. 6/20 patients had synchronous and 4/20 patients had metachronous GIT cancers. 2/6 patients who had leiomyomas with synchronous GIT cancers also presented with gastrointestinal stromal tumors (GIST). Duodenal leiomyomas showed a mean size of 0.7 cm. 1/3 patient had synchronous pancreatic adenocarcinoma. Colonic leiomyomas showed a mean tumor size of 0.6 cm. 2/37 patients had synchronous and 6/37 patients had metachronous GIT cancers. Rectal leiomyomas showed a mean tumor size of 0.9 cm. 1/6 patient had metachronous non-GIT sarcoma. Adenomatous polyps coexisted with 10/37 colonic leiomyomas, 2/6 rectal leiomyomas and 1/20 gastric leiomyoma. Immunohistochemical stains (αSMA, Desmin, CD117, DOG-1, CD34) were consistently utilized in diagnosis to exclude GIST. Conclusion Leiomyomas were most frequently found in the colon (50.0%), followed by the stomach (27.0%). Esophageal and gastric leiomyomas showed larger sizes (averaged 2.2 and 2.0 cm respectively) than duodenal, colonic, and rectal counterparts (averaged 0.7, 0.6, and 1 cm, respectively). This suggests an association between tumor locations and clinical features. Synchronous malignancies occurred in 20.2% of cases, mainly gastroesophageal/colonic adenocarcinomas. Metachronous malignancies were noted in 14.8% of cases. Given the high incidence of synchronous/metachronous malignancies (35.1%) in the gastrointestinal tract, close clinical surveillance is warranted for these patients.

Targeting esophageal carcinoma: molecular mechanisms and clinical studies.

Esophageal cancer (EC)is identified as a predominant health threat worldwide, with its highest incidence and mortality rates reported in China. The complex molecular mechanisms underlying EC, coupled with the differential incidence of esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) across various regions, highlight the necessity for in-depth research targeting molecular pathogenesis and innovative treatment strategies. Despite recent progress in targeted therapy and immunotherapy, challenges such as drug resistance and the lack of effective biomarkers for patient selection persist, impeding the optimization of therapeutic outcomes. Our review delves into the molecular pathology of EC, emphasizing genetic and epigenetic alterations, aberrant signaling pathways, tumor microenvironment factors, and the mechanisms of metastasis and immune evasion. We further scrutinize the current landscape of targeted therapies, including the roles of EGFR, HER2, and VEGFR, alongside the transformative impact of ICIs. The discussion extends to evaluating combination therapies, spotlighting the synergy between targeted and immune-mediated treatments, and introduces the burgeoning domain of antibody-drug conjugates, bispecific antibodies, and multitarget-directed ligands. This review lies in its holistic synthesis of EC's molecular underpinnings and therapeutic interventions, fused with an outlook on future directions including overcoming resistance mechanisms, biomarker discovery, and the potential of novel drug formulations.

Lymph node metastasis determined miRNAs in esophageal squamous cell carcinoma.

There is no golden noninvasive and effective technique to diagnose lymph node metastasis (LNM) for esophageal squamous cell carcinoma (ESCC) patients. Here, a classifier was proposed consisting of miRNAs to screen ESCC patients with LNM from the ones without LNM. miRNA expression and clinical data files of 93 ESCC samples were downloaded from TCGA as the discovery set and 119 ESCC samples with similar dataset GSE43732 as the validation set. Differentially expressed miRNAs (DE-miRNAs) were analyzed between patients with LNM and without LNM. LASSO regression was performed for selecting the DE-miRNA pair to consist the classifier. To validate the accuracy and reliability of the classifier, the SVM and AdaBoost algorithms were applied. The CCK-8 and wound healing assay were used to evaluate the role of the miRNA in ESCC cells. There were 43 DE miRNAs between the LNM+ group and LNM- group. Among them, miR-224-5p, miR-99a-5p, miR-100-5p, miR-34c-5p, miR-503-5p, and miR-452-5p were identified by LASSO to establish the classifier. SVM and AdaBoost showed that the model could classify the ESCC patients with LNM from the ones without LNM precisely and reliably in 2 data sets. miR-224-5p in the classifier as the top contributor to discriminate the two groups of patients based on AdaBoost, promoted ESCC cell proliferation and migration in vitro. The classifier based on these 6 miRNAs could classify the ESCC patients with LNM from the ones without LNM successfully.

Delta-CT radiomics based model for predicting postoperative anastomotic leakage following radical resection of esophageal squamous cell carcinoma.

To predict postoperative anastomotic leakage (AL) following radical resection of esophageal squamous cell carcinoma (ESCC) based on clinical data and preoperative enhanced Computed tomography(CT) radiomics of the esophagus. We retrospectively analyzed the clinicopathological and radiological data of 213 patients with ESCC who received radical resection at Xiangyang No.1 People's Hospital from July 2011 to February 2024. 3D slicer software was used in combination with Lasso extraction and 10-fold cross-validation to extract texture parameters from contrast-enhanced CT images and generate Delta-Radscores. Several models were built using logistic regression to predict postoperative AL in ESCC. In the training set, the univariate analysis confirmed that duration of surgery, surgical method, delta radscore 1, delta radscore 2, contrast enhancement patterns, peripheral lymph node metastasis, post thoracotomy pulmonary infection(PTPI), and hot pot were risk factors for ESCC-AL (P<0.05 for both). The multivariate analysis showed that delta radscore 1, delta radscore 2, PTPI, and hot pot were independent risk factors for AL (P<0.05 for all). These results were verified by the XGboost machine learning model. The combinational model based on all of the above risk factors [AUC 0.900, OR 0.0282, 95%CI 0.841-0.943] outperformed either the clinical model[AUC 0.759, OR 0.0392, 95%0.683-0.825,P<0.05] or the imaging model[AUC 0.869, OR 0.0335, 95%0.804-0.918,P=0.1277] alone in predictive efficacy. The decision curve proved that the combinational model had a higher clinical net benefit. The nomogram generated via the combinational model simplified the predictive process. The same predictions were verified in the testing set. Delta radscore 1, delta radscore 2, PTPI, and hot pot were related to ESCC-AL. The novel nomogram created using enhanced CT radiomics informed perioperative management and improved the survival quality of ESCC patients.

Long-term outcomes of endoscopic resection of superficial esophageal squamous cell carcinoma in late-elderly patients.

As the population ages, the number of elderly patients with superficial esophageal squamous cell carcinoma (ESCC) is increasing. We aimed to clarify the indications for endoscopic resection (ER) in late-elderly patients with ESCC in terms of life expectancy. Patients aged ≥75years who underwent ER for ESCC at our institution from January 2005 to December 2018 were enrolled. Clinical data, including the Eastern Cooperative Oncology Group performance status, American Society of Anesthesiologists physical status (ASA-PS), Charlson comorbidity index, and prognostic nutritional index (PNI), were collected at the time of ER. The main outcome measure was overall survival (OS). Two hundred eight consecutive patients were enrolled. The patients' median age was 78years (range, 75-89years). The 5-year follow-up rate was 88.5% (median follow-up period, 6.6years). The 5-year OS rate was 79.2% (95% confidence interval [CI], 72.2-84.8), and 5-year net survival standardized for age, sex, and calendar year was 1.04 (95% CI, 0.98-1.09). In the multivariate analysis, an ASA-PS of 3 (hazard ratio, 2.45; 95% CI, 1.16-5.17) and PNI of <44.0 (hazard ratio, 2.73; 95% CI, 1.38-5.40) were independent prognostic factors. When neither of these factors was met, the 5-year OS rate was 87.8% (95% CI, 80.0-92.9), and 5-year net survival was 1.08 (95% CI, 1.02-1.14). ER for ESCC in late-elderly patients may improve life expectancy. ER is recommended in patients with a good ASA-PS and PNI.

Patterns of upper gastrointestinal diseases among patients undergoing esophagogastroduodenoscopy at three hospitals in Asella town, Southeast Ethiopia

Upper gastrointestinal (UGI) symptoms are among the common complaints among patients visiting health facilities. Because of the scarcity of gastrointestinal endoscopy services and gastroenterologists, the pattern of common upper gastrointestinal diseases has not been well studied in the study setting. This study aimed to determine the pattern of upper gastrointestinal diseases among patients undergoing esophagogastroduodenoscopy (EGD). An institution-based cross-sectional study was conducted at three hospitals in Asella town, southeast Ethiopia. A total of 279 study subjects were included in the study. Three-fourths (74%) of the study participants had abnormal endoscopic findings. The clinical indications for endoscopic examination were dyspepsia (32.6%), peptic ulcer disease (PUD) (27.2%), suspicion of gastric cancer (13.3%), and suspicion of esophageal cancer (11.5%). The abnormal endoscopic findings were esophageal cancer (10.4%), gastric cancer (10%), duodenal ulcer (DU) (9.3%), and gastritis (8.6%). The abnormal biopsy findings were esophageal cancer (7.5%), gastric adenocarcinoma (6.4%), and gastritis (3.9%). Dyspepsia, peptic ulcer disease, and suspicion of UGI malignancies were the most common clinical indications for endoscopic examination, while esophageal cancer and gastric cancer were the most common abnormal endoscopic findings. The most common abnormal biopsy results were esophageal squamous cell carcinoma and gastric adenocarcinoma. It is advised to have a high index of suspicion for esophageal cancer and gastric cancer for patients who present with alarming upper gastrointestinal symptoms in the study setting.

Knockdown of Gas6 Exerts Anti-Esophageal Cancer Effects by Inhibiting the PI3K/AKT Pathway.

Esophageal squamous cell carcinoma (ESCC) is a malignant tumor of the digestive tract with strong migratory and invasive abilities. Gas6 is closely associated with the progression of many malignant tumors; however, the role of Gas6 in the progression of esophageal cancer is unclear. Here, we report that the knockdown of Gas6 inhibited esophageal cancer cell proliferation, migration, and invasion. In addition, Gas6 knockdown downregulated the levels of P-PI3K and P-AKT. Taken together, the findings confirm that Gas6 knockdown can inhibit esophageal cancer progression and can exert anti-tumor effects on esophageal cancer through the PI3K/AKT pathway.

Artificial Intelligence Revolutionizes Esophageal Squamous Cell Carcinoma Management

&lt;span lang="ES"&gt;The application of artificial intelligence in esophageal tumor pathology highlights the ongoing and significant transformative impact AI has in medicine. This article provides a comprehensive overview of AI technologies' current use in diagnosing and treating esophageal squamous cell carcinoma (ESCC). Through our research, we identified and meticulously analyzed 33 relevant academic papers and studies that contribute to this field. These papers encompass a broad spectrum of AI applications related to the management of esophageal squamous cell carcinoma. AI integration and deployment in both the diagnosis process and therapeutic interventions for tumors offer highly promising prospects, for example, in endoscopic procedures AI algorithm can process endoscopic images in real-time to identify abnormalities that may be missed by the human eye, it can highlight subtle changes such as color variations, small growths or tissue anomalies, which might go unnoticed due to fatigue, distraction or human limitations in perceiving fine details. AI technologies enhance medical practice precision and effectiveness by significantly reducing the likelihood of human errors and offering practical, innovative solutions. Consequently, AI confluence with medical practice not only increases diagnosis accuracy but also improves the overall efficiency of treating esophageal squamous cell carcinoma.&lt;/span&gt;

Involved-field high-dose chemoradiotherapy with respiratory motion management for esophageal squamous cell carcinoma.

We investigated the clinical outcomes of involved-field high-dose (≥66 Gy) chemoradiotherapy (CRT) combined with respiratory motion management for esophageal squamous cell carcinoma (ESCC). Patients who underwent definitive CRT for histologically confirmed ESCC in our department between 2012 and 2018 were retrospectively analyzed. Respiratory motion management strategies included breath-holding (63%) and mask immobilization (29%) based on individual measurements of respiratory tumor motion using radiographic fluoroscopy with endoscopically placed clip markers as landmarks. We evaluated patient characteristics, treatment efficacy, failure patterns, and toxicities. We enrolled 35 patients with a prescribed dose of 66-70 Gy in 33-35 fractions. The overall response rate within 6 months post-CRT was 94.3%; the median follow-up period for survivors was 43 months. The 2-year overall survival (OS), progression-free survival, and locoregional failure-free survival rates were 51.4%, 42.9%, and 42.9%, respectively. A significant difference in OS was observed between patients with and without esophageal fistulas after CRT (p = 0.002, log-rank test). Disease failure occurred in 16 patients (45.7%), including one (2.9%) with out-of-field regional nodal failure. Major grade 3 or higher toxicities included decreased white blood cell count (48.6%), neutrophil count (34.3%), and esophageal stenosis (31.4%). No grade 3 or higher cardiopulmonary toxicities were observed. Bronchial/tracheal tumor compression and a higher radiotherapy dose (70 Gy) were significantly correlated with esophageal fistulas. Involved-field high-dose CRT with respiratory motion management may be a feasible treatment option for ESCC. However, a comprehensive assessment of esophageal fistula risk is required to identify suitable candidates.

TRIM33 promotes glycolysis through regulating P53 K48-linked ubiquitination to promote esophageal squamous cell carcinoma growth

Esophageal squamous cell carcinoma (ESCC) is a common fatal malignant tumor of the digestive tract; however, its pathogenic mechanism is unknown and lacks specific molecular diagnosis and treatment. Therefore, it is particularly important to identify new tumor biomarkers to enhance the early diagnosis and molecular-targeted therapy of ESCC. Here, we found that the E3 ubiquitin ligase Tripartitemotif-containing33 (TRIM33) is highly expressed in ESCC tissues and cell lines, and is associated with adverse clinical outcomes. We determined that TRIM33 drives aerobic glycolysis to promote tumor growth in vivo and in vitro. In terms of mechanism, TRIM33 binds to p53 to inhibit its stability and promote the expression of downstream glycolysis target genes GLUT1, HK2, PKM2, and LDHA. In addition, TRIM33 promotes the polyubiquitination of P53 K48-linked and proteasome degradation. Further studies have shown that the K351 site of P53 is the key site mediating the ubiquitination of P53 K48-linked to promote aerobic glycolysis in ESCC and tumor cell growth. Our results reveal that the TRIM33-P53 signal axis regulates glycolysis during ESCC and may provide a new perspective for the diagnosis and treatment of ESCC.

Integrated analysis of gene expressions and targeted mirnas for explaining crosstalk between oral and esophageal squamous cell carcinomas through an interpretable machine learning approach.

This study explores the bidirectional relation of esophageal squamous cell carcinoma (ESCC) and oral squamous cell carcinoma (OSCC), examining shared risk factors and underlying molecular mechanisms. By employing random forest (RF) classifier, enhanced with interpretable machine learning (IML) through SHapley Additive exPlanations (SHAP), we analyzed gene expression from two GEO datasets (GSE30784 and GSE44021). The GSE30784 dataset comprises 167 OSCC samples and 45 control group, whereas the GSE44021 dataset encompasses 113 ESCC samples and 113 control group. Our analysis led to identification of 20 key genes, such as XBP1, VGLL1, and RAD1, which are significantly associated with development of ESCC and OSCC. Further investigations were conducted using tools like NetworkAnalyst 3.0, Single Cell Portal, and miRNET 2.0, which highlighted complex interactions between these genes and specific miRNA targets including hsa-mir-124-3p and hsa-mir-1-3p. Our model achieved high precision in identifying genes linked to crucial processes like programmed cell death and cancer pathways, suggesting new avenues for diagnosis and treatment. This study confirms the bidirectional relationship between OSCC and ESCC, laying groundwork for targeted therapeutic approaches. This study helps to identify shared biological pathways and genetic factors of these conditions for designing personalized medicine strategies and to improve disease management.

EIF4A3-mediated oncogenic circRNA hsa_circ_0001165 advances esophageal squamous cell carcinoma progression through the miR-381-3p/TNS3 pathway

Esophageal squamous cell carcinoma (ESCC) remains a major clinical challenge due to its poor prognosis and the scarcity effective therapeutic targets. Circular RNAs (circRNAs) are crucial in cancer progression. In this study, high-throughput sequencing was employed to profile ESCC tissues, revealing that hsa_circ_0001165 is notably elevated in both ESCC tumor samples and cell lines, with its expression is positively associated with patients' TNM staging. Knockdown of hsa_circ_0001165 resulted in reduced malignant biological behavior of ESCC cells in vitro and also inhibited tumor growth in vivo. Mechanism experimental analysis found that hsa_circ_0001165 expression is positively enhanced by eukaryotic translation initiation factor 4A3 (EIF4A3). Hsa_circ_0001165 acts as a miRNA sponge for miR-381-3p, increasing the expression of tensin-3 (TNS3) through a series of related mechanism assays include dual-luciferase reporter gene, RNA Immunoprecipitation and RNA-pulldown. The downregulation in miR-381-3p expression was observed in ESCC tissues, and the cell proliferation, invasion, and migration of ESCC were suppressed. The upregulated expression of hsa_circ_0001165 modulates the miR-381-3p/TNS3 axis and promotes aggressive phenotypes of ESCC. Hsa_circ_0001165 is regarded as a encouraging biomarker and potential therapeutic target for ESCC, presenting innovative options for both diagnostic and treatment approaches.