The IL1β-NFκB-SDC4 signaling Axis promotes esophageal cancer cell proliferation and is suppressed by EGCG.

Exploring the dynamics of symptom networks in esophageal cancer patients during chemotherapy: a cross-lagged panel network analysis.

Nucleic acid therapy: Emerging therapeutic strategies and challenges in esophageal cancer.

Evodia rutaecarpa, a traditional Chinese medicine (TCM), possesses high medicinal value and has shown great potential in the treatment of tumors and Alzheimer's disease. However, its active components against esophageal cancer and the underlying molecular mechanisms remain unclear. In this study, Ultra Performance Liquid Chromatography-Orbitrap-Mass Spectrometry (UPLC-Orbitrap-MS) was used to analyze the chemical components of Evodia rutaecarpa. Key components were identified through TCMSP, SwissADME, and BATMAN-TCM databases, and target prediction was performed using SwissTargetPrediction. Potential therapeutic targets were retrieved from OMIM, GeneCards, and TTD databases. Cytoscape and STRING were used to construct a "medicine-component-target" network, followed by GO/KEGG enrichment analysis. Molecular docking and dynamics simulations were performed with Schrödinger Maestro. In vitro validation was done using CCK-8, EdU, IF assays, flow cytometry, and Western blot analysis on esophageal squamous cell carcinoma cells. Through this study, 13 active components and 127 potential targets were identified. GO/KEGG analysis revealed key roles in cell cycle regulation. 6-hydroxyluteolin, isorhamnetin, and rutaecarpine were identified as major active components. Molecular dynamics simulations confirmed strong binding to key targets (CDK2, SRC, EGFR). In vitro experiments demonstrated that 6-hydroxyluteolin and isorhamnetin significantly inhibited cell proliferation, upregulated γ-H2AX expression levels, induced cell cycle arrest, and ultimately induced apoptosis. We found that Evodia rutaecarpa exerts anti-esophageal cancer effects through multiple components, targets, and pathways, thereby providing a theoretical basis for the potential application of Evodia rutaecarpa in the treatment of esophageal cancer.

Microbial crosstalk along the oral-gut axis: organ-specific oncogenic adaptations of Porphyromonas gingivalis and Fusobacterium nucleatum.

Esophagectomy is a key treatment for esophageal cancer but carries a high risk of postoperative complications, some of which are potentially preventable through optimized hemodynamic management. Goal-directed fluid therapy individualizes cardiac output targets but often applies fixed blood pressure thresholds and is discontinued before major postoperative fluid shifts occur. Extending goal-directed fluid therapy into the postoperative period with individualized blood pressure thresholds may address these limitations. In this single-center, prospective, blinded, randomized controlled trial, patients undergoing esophagectomy were randomized 1:1 to either extended goal-directed fluid therapy or standard care. In the extended goal-directed fluid therapy group, cardiac output was optimized and mean arterial pressure threshold was the individual patient's nighttime baseline. The protocol continued from tracheal intubation through to 7:00 am the following morning. The primary outcome was total postoperative morbidity, measured by the Comprehensive Complication Index at day 30. Of 100 patients (49 extended goal-directed fluid therapy group, 51 standard group), extended goal-directed fluid therapy was associated with a higher fluid balance (2,517 ± 1,194 ml vs. 2,001 ± 1,114 ml; mean difference, 516 ml; 95% CI, 57 to 974; P = 0.028), increased norepinephrine use (median, 7,894 μg [interquartile range, 3,946-13,793] vs. 4,611 μg [interquartile range, 2,138 to 7,296]; P < 0.001), and higher mean arterial pressure (mean difference, 3 mmHg; 95% CI, 1 to 5; P = 0.011). At day 30, the mean Comprehensive Complication Index did not differ between groups (39.0 ± 20.0 vs. 39.2 ± 21.0; mean difference, -0.2; 95% CI, -8.6 to 8.1; P = 0.95). Despite achieving protocol-driven treatment differences, extended and individualized goal-directed fluid therapy did not reduce postoperative complications after esophagectomy.

This study aimed to investigate the function of KLF11 in regulating radiosensitivity (RT) in esophageal squamous cell carcinoma (ESCC) and to elucidate the underlying mechanisms. A nude mouse ESCC xenograft model was established by injecting KYSE150 cells into the left dorsal flank. Cell proliferation was assessed using cell counting kit-8 (CCK-8) and colony formation assays, while DNA damage was evaluated via a neutral comet assay. Key gene and protein expression levels were analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting, and immunohistochemistry. Additionally, coimmunoprecipitation and immunofluorescence were employed to validate proteinprotein interactions. KLF11 expression was upregulated in both ESCC and RT-resistant tissues. At the cellular level, KLF11 expression was higher in ESCC cell lines than in the normal esophageal epithelial cell line HET-1A, with the most pronounced upregulation in KYSE150 cells and the least in TE1 cells. Notably, KLF11 knockdown under ionizing radiation exposure suppressed proliferation and colony formation, promoted apoptosis, and increased the expression of the DNA damage marker γ-H2AX as well as overall DNA damage levels in KYSE150 cells. Conversely, KLF11 overexpression in TE1 cells led to the opposite phenotype, suggesting that KLF11 confers RT resistance in ESCC by mitigating DNA damage. Further investigations revealed that KLF11 primarily repairs RT-induced DNA damage through the homologous recombination (HR) pathway rather than through nonhomologous end joining (NHEJ). Additionally, the expression of MDM2, E2F1, and RAD51 was significantly elevated in ESCC and RT-resistant ESCC tissues. Mechanistically, KLF11 promotes MDM2 expression, which inhibits E2F1 ubiquitination, thereby stabilizing E2F1 protein levels and enhancing RAD51-mediated HR repair, ultimately leading to RT resistance in ESCC. This study elucidates the critical role and molecular mechanism through which KLF11 drives radiotherapy resistance in ESCC by regulating the MDM2/E2F1 axis and enhancing HR repair, thereby providing a solid theoretical foundation and potential target for the development of KLF11-targeted radiosensitization therapies for ESCC.

Breath-based esophageal cancer diagnosis using an electronic nose with multimodal sensor array and machine learning

The purpose of this study was to explore the feasibility of predicting the main pathologic response (MPR) after neoadjuvant therapy (NAT) for locally advanced esophageal squamous cell carcinoma (LAESCC) using computed tomography (CT) imaging. From January 2022 to December 2023, a retrospective study was conducted on 150 patients who underwent neoadjuvant therapy and radical resection of R0 esophageal cancer in our hospital. Before and after neoadjuvant therapy, the tumour volume (TV) was manually delineated using an enhanced CT image background processor combined with MIMINICS reconstruction software, and the tumour volume regression rate (TVRR) was calculated. Binary logistic regression was used to analyse the factors influencing the postoperative pathological MPR using univariate and multivariate analyses. Determine the predictive value of TVRR through the receiver operating characteristic curve. The mean baseline tumor volume regression ratio was 42.8% (± 22.0). Multivariate analysis revealed that the neoadjuvant therapy mode, tumour volume after neoadjuvant therapy (TV after NAT) and TVRR were independent factors affecting the postoperative pathological MPR. According to the receiver operating characteristic (ROC) analysis, the TVRR showed good predictive value for the postoperative pathological MPR (AUC = 0.828, sensitivity = 85.7%, specificity = 71.2%, p < 0.001), and the cut-off value determined by the Youden index was 42.61%. Subgroup analysis indicated that TVRR had good predictive efficacy for postoperative pathological MPR in different neoadjuvant treatment modes and various tumour locations in the thoracic segment. The TVRR before and after neoadjuvant therapy for esophageal squamous cell carcinoma is an independent factor influencing the postoperative pathological MPR and has good predictive efficacy.

Metabolic reprogramming is a hallmark of cancer that promotes tumor progression and immune evasion. Here, we identify a NIPAL1-driven metabolic-epigenetic circuit in esophageal squamous cell carcinoma (ESCC) that facilitates tumor growth and suppresses antitumor immunity. Mechanistically, NIPAL1 recruits the tyrosine kinase HCK to phosphorylate LDHA at Y10, enhancing glycolysis and lactate production. Lactate accumulation promotes p300-mediated histone H3K18 lactylation (H3K18la), which transcriptionally activates NIPAL1 expression, establishing a self-sustaining NIPAL1-HCK-p-LDHA-lactate-p300-H3K18la loop. This axis functions independently of NIPAL1's canonical magnesium transporter activity and promotes immune escape by impairing CD8+ T cell function. Pharmacological inhibition of HCK or p300 disrupts this loop and restores antitumor immunity, sensitizing tumors to anti-PD-1 therapy. Clinically, expression of NIPAL1, p-LDHA (Y10), and H3K18la correlates with response to immune checkpoint blockade. Our findings reveal a previously unrecognized NIPAL1-HCK-H3K18la signaling loop that integrates tumor metabolism to immune regulation, offering promising targets to improve immunotherapy efficacy in ESCC.

Esophageal squamous cell carcinoma (ESCC) remains a lethal malignancy with a poor 5-year survival rate of approximately 20%, necessitating the identification of novel therapeutic targets. Here, we show that KDM4A is significantly upregulated in esophageal squamous cell carcinoma (ESCC) and its high expression correlates with poor prognosis. Functional assays demonstrated that KDM4A promotes ESCC cell proliferation, migration, invasion, and tumor growth in vitro and in vivo. Mechanistically, KDM4A demethylates H3K9me3 at the LRG1 promoter, thereby enhancing LRG1 transcription and activating the TGF-β pathway to drive epithelial-mesenchymal transition (EMT) and cancer stemness. Knockdown of KDM4A or LRG1 suppresses these oncogenic phenotypes, while LRG1 overexpression rescues KDM4A deficiency-induced impairments. Clinically, KDM4A and LRG1 are co-overexpressed in ESCC tissues and associated with advanced tumor stage and shorter overall survival. These findings identify the KDM4A-LRG1-TGF-β axis as a critical driver of ESCC progression and a potential therapeutic target.

Esophageal adenocarcinoma (EAC), the dominant subtype of esophageal cancer in developed countries, is a growing health problem, characterized by poor patient prognosis and dismal survival due to ineffective screening tools and a lack of efficacious options targeting the interception or treatment of EAC. Despite molecular advances, molecular targeting of EAC remains elusive, suggesting the need for identifying alternative targets with improved prognostic and therapeutic value. Herein, we performed RNA-sequencing analysis in EAC and Barrett's Esophagus (BE) precursor lesions to identify isoform switching events significantly linked with all-cause and cancer-specific mortality. Patients were stratified based on histopathology alone or in combination with TP53 mutation status, the most commonly mutated gene in EAC. To gain mechanistic insight, we performed isoform-specific siRNA knockdown of two isoforms, TTLL12 and HM13, both linked to patient survival, and investigated mechanisms associated with isoform dysregulation and whether targeting specific isoforms in EAC acts synergistically to improve therapeutic potential. Isoform-specific knockdown of TTLL12 and HM13 significantly decreased the viability of two EAC cell lines, sensitized EAC cell lines to standard-of-care chemotherapy agents (paclitaxel and carboplatin) with synergy, and inhibited EAC cell migratory potential. Knockdown of the TTLL12 isoform led to activation of chaperone-mediated autophagy, which, in turn, decreased expression of CHK1 and TP53; whereas knockdown of the HM13 isoform activated the unfolded protein response and induced endoplasmic reticulum stress-induced autophagy and apoptosis. In addition, HM13 isoform knockdown increased the response to an anti-PD-L1 agent, avelumab, in EAC cells, suggesting a role for isoform switching in immunosuppression. Taken together, study results suggest that isoform switching may provide novel insight for the identification of prognostic markers and inform new potential therapeutic targets for EAC treatment or prevention.

Length of stay affects long-term survival after esophageal cancer surgery: retrospective cohort study.

Development and validation of a nomogram using transaminase levels, cycle cost, and hair loss as predictive factors for the response to neoadjuvant chemotherapy in esophageal cancer.

ASO Visual Abstract: Association of Adjuvant Immunotherapy with Improved Survival for Stage II-III Esophageal Cancer: Four-Year National Perspective.

Peroral Endoscopic Myotomy (POEM) has become the first-line minimally invasive treatment for achalasia. Its short-term and mid-term (1-5years) efficacy has been consistently demonstrated, but long-term follow-up data (≥ 5years) remain limited. This systematic review and meta-analysis aims to comprehensively evaluate the long-term (median follow-up ≥ 5years) clinical efficacy and safety of POEM. Using medical literature databases, we retrieved randomized controlled trials (RCTs) and non-randomized comparative studies from the inception of the databases through September 2025. Data were extracted using the Cochrane Risk of Bias 2.0 tool and the Newcastle-Ottawa Scale to assess risk of bias for RCTs and cohort studies, respectively. Meta-analyses were conducted using either fixed-effect or random-effects models. A total of 16 studies involving 2421 patients (50.4% male) were included, with a median follow-up duration of 72months (range, 60-144months). The pooled clinical success rate was 87.1% (95% CI 82.4-91.8%; I2 = 84.2%). The pooled incidence of endoscopically detectable reflux esophagitis was 24.2% (95% CI 11.6-36.8%; I2 = 85.4%), whereas symptomatic reflux was inconsistently reported, with a pooled incidence of 27.2% (95% CI 19.2-35.3%; I2 = 83.6%). Long-term follow-up reported 2 cases of Barrett's esophagus and isolated cases of esophageal cancer. POEM has demonstrated consistent long-term efficacy and safety. Postoperative symptomatic reflux is the most common long-term complication, while the risks of Barrett's esophagus and peptic stricture remain low. POEM represents a reliable first-line treatment option; however, further multicenter prospective studies are needed to validate its long-term efficacy and safety.

Numerous studies have investigated prognostic factors for esophageal cancer after curative surgery; however, little is known about the risk factors for non-esophageal cancer-related death. This study identifies predictors of non-esophageal cancer mortality following esophagectomy. We retrospectively analyzed 398 patients who underwent thoracic subtotal esophagectomy for thoracic esophageal or esophagogastric junction cancer from 2009 to 2022. Patients with non-curative resection, special histology, or in-hospital death were excluded. Cause-specific Cox regression was used to assess predictors of non-esophageal cancer-related death. The cumulative incidence function (CIF) was estimated while taking competing risks into account, and Gray's test was applied for group comparisons. During follow-up, 181 patients died: 118 from esophageal cancer, and 63 from other causes. Non-esophageal cancer-related deaths were due to respiratory diseases (n = 23), second cancers (n = 15), and other causes (n = 25). Patients who died of non-esophageal cancer-related causes had lower Geriatric Nutritional Risk Index (GNRI) and body mass index, were older, and more frequently had hypertension compared with the other groups. CIF analysis revealed that non-esophageal cancer-related deaths increased gradually over 10years and beyond, while respiratory-related deaths tended to occur within the first 10years. Multivariable analysis revealed that age, percent vital capacity (%VC), and GNRI were independent predictors. Lower GNRI and %VC were independent predictors of non-esophageal cancer-related death among patients undergoing curative esophagectomy for esophageal cancer. Assessment of preoperative nutritional and pulmonary status may help identify vulnerable patients and guide postoperative management and supportive care.

Glucagon-like peptide 1 receptor agonists (GLP1RAs) are widely used for the treatment of type 2 diabetes mellitus (T2DM) and, at higher doses, obesity. Both T2DM and obesity are associated with a higher risk of cancer, which can be reduced by intentional weight loss, whereas effects of a reduction in hyperglycaemia are uncertain. GLP1RAs might have further direct effects, either beneficial or detrimental, on the development of specific malignancies. Evidence from preclinical and clinical studies suggests heterogeneous effects of GLP1RAs on cancer risk: the incidence of hepatocellular, oesophageal, endometrial, ovarian and prostate cancers might be reduced, whereas safety concerns persist with respect to thyroid (both medullary and non-medullary) carcinomas. Conversely, initial concerns on the risk of pancreatic cancer have not been confirmed. Nonetheless, the interpretation of current data is limited by detection and prescription biases in observational studies as well as insufficient follow-up and number of events in randomized trials. In this Review, we summarize current preclinical and clinical evidence, showing that the risk-benefit profile of GLP1RAs remains favourable in individuals withT2DM and obesity, although caution is warranted in those with a low cardiometabolic risk, for whom the potential risks of cancer might outweigh any expected benefits; conversely, the potential use of GLP1RAs as adjuvant therapies for certain forms of cancer needs to be further investigated.

Reflex biomarker testing, where molecular assays are automatically requested at diagnosis, has been proposed to accelerate cancer care. However, its operational and clinical impact across tumor types has not been systematically evaluated. A systematic review following PRISMA guidelines was conducted. MEDLINE, Embase, and gray literature (January 2000-August 2025) were searched for studies comparing reflex and clinician-initiated biomarker testing. Eligible studies reported quantitative outcomes for laboratory turnaround time, testing initiation intervals, or time to treatment. Thirty-two studies met inclusion criteria, spanning lung, skin, esophageal, breast, ovarian, colorectal, and hematological cancers. Reflex testing consistently shortened key intervals in diagnostic and treatment pathways. In non-small-cell lung cancer (n = 20), reductions were observed in turnaround time (1-38 days), initiation/request intervals (13-29 days), and time to treatment (1-44 days). Efficiencies increased use of first-line biomarker-directed therapy by 10-47%. Operational benefits included higher test uptake (7-50% increase) and lower failure rates (10-14% reduction). The magnitude of benefit varied by tumor type, biomarker panel, and implementation strategy. Reflex biomarker testing improves diagnostic efficiency and first-line therapy uptake across cancers. Its benefits are context-dependent, highlighting the need for tailored implementation strategies and evaluation of financial and clinical impact.

Chemotherapy-induced neutropenia is a serious adverse event. Combination chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF) is an effective neoadjuvant therapy for esophageal cancer, but it is associated with a high incidence of Grade 4 neutropenia. In previous study, we identified associations between genetic variants and severe neutropenia. The aim of this study was to explore genetic factors related to pharmacokinetics and endogenous antioxidant defense mechanisms that may be associated with the development of Grade 4 neutropenia in esophageal cancer patients treated with DCF chemotherapy using two independent cohorts. We conducted a retrospective pharmacogenetic analysis using DNA samples from the National Cancer Center Biobank in Japan. Two independent cohorts of esophageal cancer patients treated with the DCF chemotherapy were analyzed: an exploratory cohort (n = 157) and a validation cohort (n = 121). Single nucleotide polymorphisms (SNPs) in genes related to docetaxel pharmacokinetics and the Keich-like ECH-associated protein 1-Nuclear factor erythroid2-related factor 2 (Keap1-Nrf2) antioxidant system were examined. A total 53 (33.8%) and 62 (51.2%) patients developed Grade 4 neutropenia in exploratory and validation cohort, respectively. Multivariate analysis revealed that age, Adenosine triphosphate-binding cassette (ABC) G2 rs2231137G > A and Nuclear factor, erythroid 2 like 2 (NFE2L2) rs35652124C > T were significant in exploratory cohort, while baseline absolute neutrophil count and NFE2L2 rs35652124C > T were significant in the validation cohort. NFE2L2 rs35652124C > T was identified as an independent predictive genetic factor for Grade 4 neutropenia in esophageal cancer patients treated with DCF chemotherapy.