While severe postoperative complications (SPCs) impact cancer prognosis, their effect on locally advanced esophageal squamous cell carcinoma (ESCC) patients with varying immunonutritional statuses after minimally invasive esophagectomy (MIE) is unclear.

This retrospective study analyzed 442 patients with locally advanced ESCC who underwent MIE, investigating the relationship between SPCs and survival based on preoperative immunonutritional status, determined by the prognostic nutritional index (PNI). Nomograms were developed for patients with preserved immunonutritional status using Cox regression, and their performance was assessed.

Of the patients, 102 (23.1%) experienced SPCs after MIE. Five-year overall survival (OS) and disease-free survival (DFS) were significantly different between SPCs and non-SPCs groups (p < 0.001). In the preserved immunonutritional group, SPCs significantly reduced 5-year OS (p = 0.008) and DFS (p = 0.011), but not in the poor immunonutritional group (OS p = 0.152, DFS p = 0.098). Multivariate Cox regression identified SPCs as an independent risk factor for OS (HR = 1.653, p = 0.013) and DFS (HR = 1.476, p = 0.039). A nomogram for predicting OS and DFS in preserved immunonutritional patients demonstrated excellent performance.

SPCs significantly affect prognosis in ESCC patients with preserved immunonutritional status after MIE. Nomograms based on SPCs can predict OS and DFS in these patients.

Esophageal cancer (EC) is the eleventh most commonly diagnosed cancer, and its prognosis remains poor. Several challenges remain for improving the clinical outcomes of EC, and improving technologies for early detection, diversifying treatment options, and advancing personalized treatment are essential. Alterations in the intestinal and esophageal microbiota are associated with the pathogenesis and progression of EC; for instance, Fusobacterium nucleatum is important in the pathogenesis and progression of esophageal squamous cell carcinoma. Therefore, a novel diagnostic biomarker may be identified using the intestinal microbiota. Furthermore, targeting the intestinal and esophageal microbiota may help in the early detection of EC, use of a novel prognostic biomarker, and even the detection of a therapeutic target, resulting in a more individualized therapeutic approach for EC. In this review, we summarize the clinical research focused on the intestinal and esophageal microbiota in EC development and its treatment, and discuss the challenges in the clinical application of intestinal and esophageal microbiota.

Esophageal cancer is one of the most migratory, invasive, and lethal malignancies and has a poor prognosis, highlighting the urgent need to develop more effective drugs for its treatment. Given that PSMD14 and HDAC play an important role in the treatment of esophageal cancer, thiolutin is used as a lead compound to design and synthesize a series of dual-target PSMD14/HDAC small molecule inhibitors, aiming to discover more effective anti-esophageal cancer drugs. Through the in vitro screening of PSMD14/HDAC enzyme inhibitory activities of a series of thiolutin derivatives, it was found that compound 8b, with a linker length of 8 and a Zn2+-chelating group of 1,2-phenylenediamine, exhibited the most balanced inhibitory activity against PSMD14/HDAC.The impact of 8b on PSMD14/HDAC at the cellular level was evaluated, and its drug-like properties were further assessed in vivo. Compound 8b demonstrates balanced dual-target activity (PSMD14 IC50 = 238.7 ± 27 nM, HDAC1 IC50 = 141.2 ± 10.3 nM) and excellent cytotoxicity against esophageal cancer cells (IC50 = 30-250 nM), effectively reversing epithelial-mesenchymal transition in cancer cells. Moreover, 8b exhibited excellent pharmacokinetic characteristics. More importantly, in a nude mouse xenograft model with subcutaneous transplantation of KYSE 30 cells, compound 8b (0.8 mg/kg, BID, PO, TGI = 81 %; 0.8 mg/kg, Q3D, SC, TGI = 77 %) significantly inhibited tumor growth, outperforming single-agent or combination treatments, thereby highlighting the therapeutic advantages of dual-target inhibition. These findings highlight the potential of dual-target PSMD14/HDAC inhibitors as a promising strategy for developing anti-esophageal cancer drugs.

Associations of adiposity with risks of oesophageal squamous cell carcinoma (ESCC) and non-cardia stomach cancer, both prevalent in China, are still inconclusive. While adiposity is an established risk factor for colorectal cancer, the relevance of fat-free mass and early-adulthood adiposity remains to be explored. The prospective China Kadoorie Biobank study included 0.5 million adults (aged 30-79 years) from 10 areas in China. Participants' body size and composition were measured at baseline and at resurveys (amongst a subset). After >10 years of follow-up, 2350, 3345 and 3059 incident cases of oesophageal (EC), stomach (SC) and colorectal (CRC) cancers were recorded, respectively. Cox regression was used to estimate hazard ratios (HRs) for these cancers in relation to different adiposity traits. General and central adiposity were inversely associated with EC (primarily ESCC) risk, with HRs of 0.81 (95% CI 0.77-0.85), 0.76 (0.72-0.81) and 0.87 (0.83-0.92) per SD increase in usual levels of BMI, body fat percentage (BF%) and waist circumference (WC), respectively. Adiposity was also inversely associated with SC risk [HR = 0.79 (0.75-0.83) and 0.88 (0.84-0.92) per SD increase in usual BF% and WC], with heterogeneity by cardia and non-cardia subsites, and positively associated with CRC [HR = 1.09 (1.03-1.15) and 1.17 (1.12-1.22) per SD higher usual BF% and WC]. Fat-free mass was inversely associated with EC [HR = 0.93 (0.89-0.98) per SD increase] but positively associated with CRC [1.09 (1.04-1.14)], while BMI at age 25 was positively associated with all three cancers. After mutual adjustment, general adiposity remained inversely associated with EC and SC, while central adiposity remained positively associated with CRC.

Tristetraprolin (TTP) can inhibit the abnormal proliferation of malignant tumors but there are no studies involving TTP and esophageal squamous cell carcinoma (ESCC). We aimed to determine the effect of TTP on ESCC cell proliferation and to elucidate the underlying mechanism.

The human ESCC cell line, KYSE-510, and the human ESCC cell line, KYSE-150, stably infected with tetracycline-inducible expression (Tet-on-TTP and Tet-on-EV, respectively) were screened with puromycin. After Tet-on-TTP KYSE-150 cells were treated with different concentrations of doxycycline [Dox] (0, 0.5, and 1 ug/mL), the levels of TTP mRNA and protein expression were detected by real-time fluorescent quantitative PCR and western blotting, respectively. The effects of TTP on proliferation and migration were estimated by CCK-8 and Transwell assays, respectively. Cell apoptosis and cell cycle were measured by flow cytometry. Cellular apoptosis-related gene protein expression was determined by western blotting.

TTP overexpression significantly inhibited KYSE-510 and KYSE-150 proliferation. TTP overexpression also significantly inhibited KYSE-150 migration. In addition, TTP expression upregulation promoted the KYSE-150 apoptosis and induced cell cycle arrest in the G2 phase, downregulated Bcl-2 expression, and upregulated Bax expression.

TTP inhibited ESCC cell proliferation, promoted ESCC cell apoptosis, and arrested cell cycle progression in the G2 phase.

Esophageal squamous cell carcinoma is an aggressive and globally prevalent malignancy that rarely presents as submucosal tumor-like lesions, leading to significant diagnostic challenges. We present two examples of primary esophageal squamous cell carcinoma in which complete intramural invasion mimicked submucosal tumor-like lesions. Initial biopsies suggested benign hyperplasia; however, subsequent endoscopic ultrasound-guided fine needle aspiration confirmed the diagnosis of esophageal squamous cell carcinoma. Both patients received appropriate treatment and showed favorable outcomes. The histopathological feature of intramural esophageal squamous cell carcinoma, characterized by growth confined within the esophageal wall without mucosal epithelial invasion, represents an exceedingly rare and complex pattern. The diagnostic challenges presented by this form of esophageal squamous cell carcinoma highlight the critical role of detailed histopathological examination, with endoscopic ultrasound-guided fine needle aspiration being indispensable for accurate diagnosis and effective management of submucosal tumor-like lesions.

Environmental factors, including poor dietary habits and unhealthy drinking patterns, contribute to ulcerative colitis (UC). While the relationship between diet-related malnutrition and UC has been extensively explored, the impact of drinking water temperature remains largely overlooked, prompting us to investigate its influence on UC pathogenesis and explore the underlying mechanisms. In the present study, we observed that, unlike external thermal and cold therapy, varying drinking water temperatures transiently altered the internal body temperature of the digestive tract. Specifically, chronic drinking of 0°C water had significant anti-inflammatory effects and preserved the integrity of the mucosal barrier in a colitis mouse model. Mechanistically, this temperature spectrum changed the composition of the gut microbiota from inflammation-prone (25°C drinking water) to a resting pattern similar to that of the negative control. Specifically, the abundances of Blautia and Parasutterella, two beneficial genera, were strongly increased in response to 0°C water, accompanied by elevated levels of short-chain fatty acids. In contrast, drinking 40°C water had opposite effects on all the examined parameters and generally aggravated the development of colitis. This study is the first to demonstrate how modifying the temperature of habitual drinking water can modulate colitis progression, providing a novel and noninvasive approach to UC management. Specifically, chronic consumption of 0°C water alleviated the severity of colitis, whereas 40°C water aggravated the disease. Therefore, by focusing on commonly consumed drinking water temperatures, our findings suggest that this simple intervention could be a safe, convenient, and effective therapeutic strategy.

Esophageal cancer ranks among the most lethal malignancies globally, with China accounting for more than half of worldwide esophageal squamous cell carcinoma (ESCC) cases. Late-stage diagnosis frequently precludes surgical intervention, contributing to poor outcomes. While precise clinical assessment is essential for treatment planning, therapeutic responses and prognosis exhibit substantial inter-patient heterogeneity, underscoring the urgent need for reliable biomarkers to enhance prognostic accuracy and guide personalized therapeutic strategies. Radiomics, an emerging field that extracts high-dimensional features from medical images, provides non-invasive approaches to improve diagnostic accuracy, predict survival, monitor adverse events, detect recurrence, and optimize treatment strategies. Radiomics has shown promising potential in the modern management of ESCC. Here, we review the critical contributions of radiomics to ESCC research and clinical practice, examining its workflow, applications, strengths, and limitations. Radiomics represents a compelling frontier with substantial potential to advance precision medicine for ESCC patients.

Identification and verification of clinically actionable molecular variations to refine currently adopted risk-stratified treatment strategy for esophageal squamous cell carcinoma (ESCC) is urgently needed. Here, we evaluated FGFR3 amplification status by fluorescence in situ hybridization (FISH) performed on tissue microarrays and its prognostic value in 526 ESCC patients. FGFR3 amplification was found in 3.0% (16/526) of ESCC patients enrolled in this study cohort. Intratumor heterogeneity and metastatic heterogeneity of FGFR3 amplification were found in 10% (2/20) and 40% (2/5) FGFR3 amplified ESCC cases, respectively. No statistically significant associations were found between FGFR3 amplification status and common clinicopathological features. Survival analyses demonstrated that FGFR3 amplification was associated with a worse disease-free survival (DFS) and overall survival (OS) (DFS, P = 0.008; OS, P = 0.027). Univariate and multivariate analyses revealed that invasive depth was significantly associated with DFS (P = 0.001, HR: 1.498, 95% CI: 1.172-1.914) and OS (P = 0.002, HR: 1.482, 95% CI: 1.159-1.894), and FGFR3 amplification was significantly associated with DFS (P = 0.020, HR: 2.065, 95% CI: 1.120-3.808) and tend to associate with OS (P = 0.070, HR: 1.756, 95% CI: 0.954-3.233). Furthermore, when patients were stratified into stage I-II group and stage III-IV group, the adverse effect of FGFR3 amplification on prognosis was presented in stage III-IV patients (DFS, P = 0.0047; OS, P = 0.029) rather than stage I-II patients (DFS, P = 0.46; OS, P = 0.53), indicating that the prognostic value of FGFR3 amplification may relying on clinical stage. Our findings might provide a better understanding of the FGFR3 amplification status in ESCC patients and add further insights into its potential prognostic value.

Esophageal cancer is a major global health challenge, with high incidence and mortality due to the lack of rapid and sensitive diagnostic tools and specific biomarkers. Cancer-cell-derived extracellular vesicles (EVs) carry unique proteins and nucleic acids, making them valuable sources of cancer biomarkers. We report an integrated method that combines an ultrafast exosome isolation system (EXODUS) with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to detect EVs and identify protein biomarkers for diagnosing and monitoring esophageal squamous cell carcinoma (ESCC). EVs derived from 20 mL culture medium supernatant of ESCC cells with varying degrees of differentiation serve as analysis models. We use EXODUS to isolate EVs rapidly. We then analyze the intact EVs using MALDI-TOF MS, which provides cell line-specific EV fingerprints in minutes. These protein fingerprints allow the discrimination of ESCC from normal control cells and enable the classification of ESCC based on the degree of cell differentiation. We explore critical EV biomarker peaks for ESCC diagnosis (5555 m/z, 8603 m/z, etc.) and monitoring (2268 m/z, etc.). Potential EV biomarker candidates, including YBX1, DIRAS2, HIST1H2AH, and MYBBP1A, are identified through tandem mass tag (TMT) proteomics. We tentatively assign the protein identities of EV marker peaks by correlation with the TMT proteomics. Applying this method to plasma-derived EVs shows promise for rapid, minimally invasive diagnosis and monitoring of ESCC.

Accumulating evidence highlights the pivotal role of microbiomes in cancer development. To elucidate the esophageal microbiome's characteristics during esophageal squamous cell carcinoma (ESCC) progression, normal tissues from 13 healthy controls (HC), paired esophageal squamous intraepithelial neoplasia (ESIN) lesional and adjacent (ESINA) tissues from 10 ESIN individuals, and ESCC lesional and adjacent (ESCCA) tissues from 12 ESCC individuals were collected. Following 16S rRNA and ITS sequencing, analyses encompassed α/β-diversity assessments, shared species identification, Type-I Taylor's Power Law Extensions (TPLE), linear discriminant analysis effect size (LEfSe), co-occurrence networks, receiver operating characteristic (ROC) curve analysis, and functional predictions. Distinct microbial signatures characterized HC, precancerous, and cancerous groups. The ESIN group exhibited unique microbial features, including diminished bacterial and fungal species sharing relative to the ESINA group and maximal b values in TPLE for both taxa. Despite the absence of significant bacterial composition differences between HC and ESIN in β-diversity analysis, notable alterations in the oral microbiome were observed. ESIN was marked by Lactobacillus and Aspergillus enrichment, while ESCC was predominantly associated with Fusobacterium, Streptococcus, and Alternaria. Disease progression led to shifts and reductions in species co-occurrence network interactions. Aspergillus demonstrated potential diagnostic value for ESIN, and its ratio to pathogenic functional clusters within network analysis significantly enhanced ESCC detection accuracy. Functional predictions revealed stage-specific pathway enrichments. These findings delineate microbiome alterations across ESCC stages, emphasizing ESIN-specific microbial shifts that may inform microbiome-based strategies for early detection and intervention.

This study collected esophageal tissues through gastroscopic biopsy and conducted sequencing and analyses to explore the diversity, heterogeneity, key microbial composition, interaction networks, and functional predictions of resident bacteria and fungi in esophageal squamous cell carcinoma (ESCC) progression. The esophageal squamous intraepithelial neoplasia group showed the highest heterogeneity in oral microbiome and fungi, with certain species potentially contributing to ESCC progression. Targeting the oral microbiome in high-risk populations may thus provide a valuable approach for improving early diagnosis and potentially intervening in disease progression.

Esophageal cancer is a prevalent malignancy with limited treatment options. The study aimed to understand the role and mechanism of NEK7 in esophageal cancer development.

RNA sequencing compared esophageal cancer tissues with adjacent tissues, and real-time PCR validated NEK7 expression. Co-IP identified NLRP3 as NEK7's binding partner. We also study the effects of NEK7 knockdown on cell viability, apoptosis, migration, invasion, and the expression of NLRP3/PD-L1 in esophageal carcinoma cell lines. TIMER 2.0 analyzed immune infiltration. An animal model was used to investigate the impact of NEK7 knockdown on tumor size, survival rates, and immune cell infiltration. Licochalcone B blocked NEK7/NLRP3, enhancing CD8 T cell-mediated tumor killing. PD-1's role in T cell viability was also assessed.

NEK7 was observed to be markedly elevated in both tumor tissues of esophageal cancer and EC109 cells. Moreover, silencing NEK7 reduced cell viability, migration, and invasion, while enhancing cell apoptosis in vitro. Knockdown of NEK7 caused a notable reduction in levels of NLRP3 and PD-L1 in EC109 cells. NEK7 expression showed a positive correlation with immune cell infiltration. Knockdown of NEK7 decreased PD-L1 expression, while upregulation of NEK7 increased PD-L1 expression, then reversed by NLRP3 knockdown. In animal studies, NEK7 knockdown reduced tumor size and volume while improving survival. It also promoted CD4 and CD8 T cell infiltration while inhibiting Treg cells and PD-1 + CD4 and CD8 T cells. Licochalcone B blocked NEK7/NLRP3 binding, decreased cell viability of EC109 cells, and enhanced the activity of co-cultured CD8 T cells. Furthermore, Licochalcone B and anti-PD-1 treatment increased the killing ratio of EC109 cells.

In conclusion, NEK7 is a key regulator in the progression of esophageal cancer and the immune evasion. Targeting the NEK7/NLRP3 pathway may have therapeutic potential for the treatment of esophageal cancer.

Esophageal squamous carcinoma is a prevalent cancer worldwide, particularly in China. Few studies have compared the treatment effects of neoadjuvant immunochemotherapy and neoadjuvant chemoradiotherapy on the long-term prognosis of patients with esophageal squamous carcinoma. This study analyzed the 3-year overall survival rate of patients with locally advanced esophageal squamous carcinoma treated with esophagectomy after neoadjuvant immunochemotherapy or neoadjuvant chemoradiotherapy.

A total of 309 patients with esophageal squamous carcinoma who underwent neoadjuvant chemoradiotherapy between 2010 and 2020 and 88 who underwent neoadjuvant immunochemotherapy between 2019 and 2020 at Zhejiang Cancer Hospital were included in this study. Propensity score matching with a 1:1 ratio and a caliper of 0.02 was used to balance the baseline characteristics.

The study included 397 patients with locally advanced thoracic segmental esophageal squamous carcinoma, including 88 who received neoadjuvant immunochemotherapy and 309 who received neoadjuvant chemoradiotherapy. After propensity score matching, there were no significant differences in pathologic complete response between the 2 groups (21.3% vs 33.3%, χ2 = 2.148, P = .143), and the neoadjuvant immunochemotherapy group demonstrated a greater 3-year overall survival rate (73.8% vs 54.8%, P = .003), particularly for patients with a primary stage Ⅲ diagnosis (T3N1M0, T1-3N2M0) or an initial suspicion of lymph node metastases. Pathologic complete response emerged as a reliable predictor of long-term outcomes in patients receiving neoadjuvant chemoradiotherapy, but not in those receiving neoadjuvant immunochemotherapy.

Neoadjuvant immunochemotherapy was associated with improved long-term prognosis in patients with a primary stage Ⅲ diagnosis or an initial suspicion of lymph node metastases. Neoadjuvant immunochemotherapy plus surgery emerged as an effective therapeutic strategy for treating locally advanced thoracic segmental esophageal squamous carcinoma.

The NEOCRTEC1601 trial aimed to evaluate the efficacy and safety of paclitaxel in combination with cisplatin and 5-fluorouracil (TPF) as an induction chemotherapy for borderline-resectable esophageal squamous cell carcinoma (BR-ESCC). This study presents an updated 5-year analysis to further elucidate the impact of TPF chemotherapy followed by surgery.

This study was conducted as a single-center, phase II clinical trial. Eligibility was extended to patients diagnosed with BR-ESCC, characterized by a primary tumor or bulky lymph nodes with potential invasion into adjacent organs. The treatment protocol commenced with TPF chemotherapy, followed by surgery, if the tumor was deemed resectable, or by concurrent chemoradiation in cases where resection was not feasible. This updated report delineates the 5-year overall survival (OS) and progression-free survival (PFS) rates.

Surgery was performed on 27 patients (57.4%), and R0 resection was observed in 26 patients (53.2%). Pathologic complete response was confirmed in four patients (8.5%). Following a minimum follow-up period exceeding 60 months for all patients, the total number of deaths was 31 (65.96%). The OS and PFS for the R0 group were significantly longer than those for the non-R0 group (median OS: 53.0 months vs. 13.9 months, HR: 0.36, 95% confidence interval [CI]: 0.17-0.76, P = 0.0032; median PFS: 50.84 months vs. 5.42 months, HR: 0.40, 95% CI 0.19-0.84, P = 0.0076). The 5-year OS rate was 50.0% (34.0%-73.4%) for the R0 group compared to 19.0% (7.9%-46.0%) for the non-R0 group (HR: 0.36, 95% CI: 0.17-0.79, P = 0.0041).

Long-term follow-up confirmed that the OS and PFS were significantly improved in patients who underwent R0 resection compared to those who did not. The 5-year OS rate for patients who achieved R0 resection was 50.0%. R0 resection might be an independent prognostic factor for OS. To further improve the R0 resection rate and prognosis, more effective induction treatment regimens need to be explored.

The progression of Esophageal Squamous Cell Carcinoma (ESCC) can be dissected with greater precision using multi-omics and single-cell RNA sequencing (scRNA-seq) compared to traditional methodologies. These advanced approaches enable a comprehensive understanding of cellular heterogeneity and molecular dynamics, offering higher resolution insights into cancer development. Moreover, analyzing transcription factor regulatory networks provides innovative avenues for identifying cancer biomarkers and therapeutic targets, driving new perspectives in cancer research.

To explore the molecular mechanisms and cellular dynamics of ESCC.

Utilizing bulk-RNA-seq and single-cell transcriptomics, our study identify major cell types, transcriptomic gene and function changes during ESCC progression. Validation experiments in clinical sample tissues and ESCC cell lines to confirm core regulation factor in ESCC.

We identified six major cell types in the ESCC scRNA-seq dataset and revealed profound shifts in cellular composition and transcriptional profiles. Notably, STAT3 was found to be a core regulator in ESCC and negatively regulated LHPP expression at promoter sites. Elevated STAT3 and reduced LHPP expression were consistently observed in patient samples, highlighting their inverse relationship in ESCC pathogenesis.

This study integrates bulk-seq and scRNA-seq data to reveal the pivotal role of STAT3 in ESCC. STAT3 negatively regulates LHPP expression, driving tumor progression. These findings underscore the therapeutic potential of targeting STAT3 in ESCC.

ESCC, single-cell transcriptomics, ESCC microenvironment, STAT3.

Long non-coding RNAs (lncRNAs) have emerged as crucial regulators of cancer development and progression. Among them, Differentiation Antagonizing Non-Protein Coding RNA (DANCR) has been implicated in various malignancies, including esophageal squamous cell carcinoma (ESCC). This study explores the clinical characteristics, prognostic implications, functional roles, and molecular mechanisms of DANCR in ESCC. Our results demonstrate that DANCR is highly expressed in ESCC, and acts as an oncogene in ESCC both in vitro and in vivo. Through bioinformatics analysis and experimental validation, we revealed that DANCR promotes ESCC progression by sponging miR-3193 and regulating its target gene DDIT3 expression. These findings highlight the critical role of DANCR in the development of ESCC and suggest its potential as a prognostic predictor and drug therapeutic target.

The transcriptional cyclin-dependent protein kinase 12 (CDK12), a potential target in various cancers, was recently discovered with a dramatic amplification in esophageal cancer (EC). In this study, we conducted an online database analysis that revealed CDK12 to be overexpressed in esophageal squamous cell carcinoma (ESCC) tissue samples from patients. Furthermore, survival analysis indicated that CDK12 can serve as a prognostic indicator for ESCC patients. In addition, CDK12 knockdown had been shown to reduce the proliferation of ESCC cells. The present study also details the design, synthesis, and biological evaluation of new CDK12 inhibitors which bear the scaffold of 4-(2-(methylamino)thiazol-5-yl)pyrimidin-2-amine. Among the synthesized compounds, H63 has been identified as a potent inhibitor of CDK12 with excellent anti-ESCC activity. Mechanistically, H63 blocked transcription elongation, downregulated the G1-phase core genes to induce cell cycle arrest, and altered the CDK12-ATM/ATR-CHEK1/CHEK2 signaling axis to cause DNA damage. In addition, H63 exhibited favorable pharmacokinetic properties, good safety, and prominent anti-ESCC activity in vivo. The present study suggests that CDK12 is a promising target for ESCC treatment, and H63 is a promising candidate for further clinical development as an anti-ESCC drug.

Esophageal squamous cell carcinoma (ESCC) is the primary histological subtype of esophageal carcinoma, yet research on environmental exposure risks and associated metabolic alterations preceding ESCC is limited. In a nested case-control cohort of 396 adults (199 diagnosed with ESCC and 197 healthy controls (HC)), we combined exposomics and metabolomics to assess circulating chemical residues and early serum metabolic changes linked to ESCC risk. A cell experiment further evaluated the proliferative impact of 1H,1H,2H,2H-perfluorooctanesulfonic acid (6:2 FTS), identifying it as a risk factor for ESCC, primarily through lipid metabolism-related chronic inflammation. Significant metabolic disruptions were observed in ESCC cases, characterized by increased carnitines, phosphatidylcholines (PCs), and triglycerides (TGs) alongside reduced lysophosphatidylcholines (LPCs) and ether lysophosphatidylcholines (LPC-Os). An early-warning biomarker panel, including glutamic acid, methionine, choline, LPC-O 18:0, TG (14:0_18:2_20:5), and PC (18:0_20:4)/LPC 18:0, showed improved predictive capacity when combined with 6:2 FTS. Metabolome-exposome-wide association studies largely confirmed 6:2 FTS as a potential ESCC risk factor through lipid mediation. This study offers novel insights for ESCC prevention and early diagnosis through a combined biomarker panel integrating metabolic and environmental risk indicators.

Endoscopic laryngopharyngeal surgery is an effective treatment for superficial laryngopharyngeal cancer, particularly in cases with prior esophageal cancer treatment. Despite its frequent application, reports on the risk factors for postoperative complications are limited. This study aimed to identify the risk factors for pneumonia after endoscopic laryngopharyngeal surgery and to examine the variations in pneumonia incidence among the types of prior esophageal cancer treatment.

Patients who had a history of esophageal cancer treatment and subsequently underwent endoscopic laryngopharyngeal surgery for superficial pharyngolaryngeal cancer were retrospectively analyzed. We examined the association between postoperative pneumonia and several factors, including number of lesions; diameter of the resected lesion; and type of previous esophageal cancer treatment, such as endoscopic submucosal dissection, chemoradiotherapy, and esophagectomy.

The study included 79 patients who had a mean age of 67.4 years. Postoperative pneumonia occurred in 16.4%. Multivariate analysis showed that the pneumonia incidence significantly increased in cases with multiple lesions (OR 4.794, 95% CI 1.133-20.288, p = 0.033) and larger diameter of the resected lesion (OR 7.047, 95% CI 1.791-27.730, p = 0.005). Importantly, compared with other treatments, prior esophagectomy for esophageal cancer did not increase the pneumonia incidence.

Multiple lesions and larger lesion diameter were the significant predictors of postoperative pneumonia. Moreover, endoscopic laryngopharyngeal surgery can be safely performed even in patients who have previously undergone esophageal cancer surgery, although careful monitoring remains necessary.

According to reports from China, esophageal cancer ranked sixth in terms of morbidity and accounted for 6.26% of all cancer cases in China. This study aimed to establish an effective prognostic nomogram for non-adjuvant therapy in patients with stage I to III esophageal cancer.

We took up cases from 2010 to 2015 from the Surveillance, Epidemiology, and End Results (SEER) database and used R language software to perform Kaplan-Meier survival curve and multivariate Cox regression analysis. Furthermore, we established the nomogram for non-adjuvant therapy patients with stage I to III esophageal cancer to predict 3- and 5-year esophageal cancer-specific survival rate. The prognostic ability of the nomogram was assessed using the C-index, area under the receiver operating characteristic (ROC) curve, and calibration chart.

The esophageal cancer-specific survival rate of cancer in the lower third of the esophagus was significantly higher than that of cancers in the upper-third of the esophagus as per the Kaplan-Meier curve. Based on the multivariate Cox regression analysis, sub variables such as advanced age, stage II and III, squamous cell carcinoma, moderately differentiated (grade II), poorly differentiated (grade III), and undifferentiated (grade IV) cancer significantly increased risk of prognosis in all patients. With a total of 150 points in the nomogram, the 3- and 5-year esophageal cancer-specific survival rates were 50% and 40% respectively. The value of C-index of this model was 0.851 and the value of the area under receiver operating curve projected 1-, 3-, and 5-year esophageal cancer-specific survival rates of 0.884, 0.874, and 0.856, respectively.

The established nomogram had good prediction ability for non-adjuvant therapy patients with stage I to III esophageal cancer.

The treatment of locally advanced lower esophageal cancer/esophagogastric junction cancers still has certain limitations. This study shares a new therapeutic strategy, namely neoadjuvant arterial infusion chemotherapy combined with immunotherapy (neo-AICIT).

The data of patients who received neoadjuvant arterial infusion chemotherapy (docetaxel + cisplatin) combined with immunotherapy (tislelizumab) for locally advanced lower esophageal cancer or esophagogastric junction cancers from October 2021 to May 2023 were collected. The indicators of these patients, such as the clinical staging of tumors, treatment-related adverse events (TRAEs), the effect of neoadjuvant therapy, operative complications, tumor regression grade (TRG), progression-free survival (PFS), and follow-up time, were recorded.

A total of 12 patients received a complete neoadjuvant regimen, sequential surgery, and postoperative maintenance immunotherapy. The median age was 61.5 years. All patients suffered from squamous cell carcinoma; eight of them had lower esophageal cancer and four had esophagogastric junction cancer. The clinical staging in all patients was cT3N0-2M0G1-3. The median tumor proportion score (TPS) was 32.5%. Only grade 1 TRAEs occurred during adjuvant therapy, and the incidence was 58.3% (7/12). Postoperative complications included pulmonary infection 16.7% (2/12) and recurrent laryngeal nerve injury 16.7% (2/12). The postoperative pathology showed that 11 (91.7%, 11/12) patients had major pathological remission (MPR) with a TRG of 1-2, while 7 (58.3%, 7/12) patients had pathological complete response (pCR) with a TRG of 1. The objective response rate (ORR) was 100%. The median follow-up time was 19.5 months. Two patients had mediastinal lymph node metastasis at 18 and 20 months after operation, respectively. Tumor recurrence or metastasis was not found in other patients.

Observations of small case series suggest that neo-AICIT has good safety and efficacy in the treatment of locally advanced lower esophageal/esophagogastric cancer, and may be a promising neoadjuvant treatment option.

Patients with head and neck neoplasms (HNN) are at an increased risk of esophageal neoplasia (EN) and gastric neoplasia (GN). We aimed to assess the clinical impact and cost-utility of endoscopic screening in this population in the Western setting.

In this single-center study HNN patients eligible for curative treatment underwent screening esophagogastroduodenoscopy. We assessed the frequency, clinical, and pathological outcomes of EN and GN. The cost-effectiveness of an annual endoscopic screening for EN was evaluated from a societal perspective, using a Markov model and probabilistic sensitivity analysis. In addition, we performed a sensitivity analysis using data on the prevalence of detected EN lesions in the four largest previous Western studies on this topic.

Forty-six HNN patients met the inclusion criteria and underwent endoscopic screening. Six EN were detected in five patients (10.9%, 95% confidence interval: 1.9-19.9%). Additionally, five GN were detected in five patients. Most patients had early-stage EN or GN (90%) and were treated with endoscopic resection (80%). Endoscopic screening strategy had an incremental cost-effectiveness ratio of 39 357.8 €/quality-adjusted life years gained, being cost-effective at a willingness-to-pay threshold of two times the Portuguese gross domestic product per capita. In the sensitivity analysis, it remained cost-effective when considering the prevalence of EN reported in Germany, France, and Brazil.

An endoscopic screening program identified EN or GN in a fifth of HNN patients, most presenting at an early stage. The program implementation appears to be cost-effective in Portugal. These results may be applicable to other medium-to-high-income Western countries.

The purpose of this study was to investigate the impact of clinicopathological factors on the overall survival (OS) of advanced esophageal squamous cell carcinoma (ESCC) patients with both lymph node and distant metastasis and build a nomogram for OS prediction.

We selected 621 ESCC patients with cT1-4N1-3M1 stage without surgical treatment from the Surveillance, Epidemiology, and End Results (SEER) database and randomized (in a 7:3 ratio) to the training cohort and internal validation cohort. Another 159 patients were enrolled from the Cancer Hospital of Shantou University Medical College as the external validation cohort. A nomogram was developed based on independent risk factors that resulted from a multivariate Cox regression analysis. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to evaluate the discriminative ability and calibration curves were constructed to evaluate the calibration ability. Kaplan-Meier survival analysis and log-rank tests were then used to predict the further OS status of these patients.

The multivariate Cox regression analysis revealed that sex, T stage, radiotherapy, and chemotherapy were independent prognostic factors for ESCC patients with cT1-4N1-3M1 stage. All these factors were incorporated to construct a nomogram. The prognostic nomogram in training cohort exhibited the AUCs of 0.784, 0.746, and 0.735 for predicting 6-, 9-, and 12-month OS, respectively. Calibration curves exhibited that the nomogram-predicted OS were insistent with the actual OS. In validation cohorts, the nomogram still showed acceptable discrimination ability and calibration. All individuals were allocated into high-risk versus low-risk groups based on the median risk score of the training cohort. The OS of the high-risk group was shorter than that of the low-risk group in three cohorts.

We developed and validated an individualized survival prediction nomogram for predicting OS in ESCC patients with cT1-4N1-3M1 stage, which may help clinicians to assess the situation of advanced ESCC patients and implement further treatment.

Paracancerous tissues (PCTs) were previously considered benign regions, but recent findings reveal genomic instability in these areas. Smoking and alcohol consumption are closely associated with esophageal cancer (EC) development. This study explored the interplay between the Hippo pathway and pyroptosis in EC, PCTs, and distal normal tissues (DNTs). We used molecular epidemiological methods to analyze the effects of smoking and alcohol on these pathways. We found that key genes in both pathways were more altered in smokers and/or drinkers compared to non-smokers and non-drinkers. Additionally, we observed changes in some genes and proteins in PCTs, while the Hippo pathway and pyroptosis had not yet been influenced. We applied 4.0% alcohol combined with various concentrations of cigarette smoke extract (CSE) to PCTs cultured in vitro to observe carcinogenesis and changes in these pathways. Verteporfin, as an inhibitor of YAP, was also used in vitro culture experiments to observe its effects on cellular carcinogenesis. Among 56 EC patients, 41 had a history of smoking and/or alcohol consumption in this study. Compared to DNTs, Hippo pathway genes (Lats1, Yap, and Taz) and pyroptosis genes (Nlrp3, Asc, Gsdmd, and Caspase-1) were altered in 49 EC tissues, while changes of Lats1, Nlrp3, and Asc were observed in 47 PCTs. Additionally, 4.0% alcohol combined with 3.2%, 4.0%, and 5.8% CSE, respectively, not only induced cellular heterogeneity and even cancerous transformation, but also suppressed the Hippo pathway and pyroptosis in the PCTs cultured in vitro. Furthermore, in vitro, 9 μM verteporfin inhibited cellular heterogeneity/carcinogenesis in PCTs induced by 4.0% alcohol combined with 5.8% CSE through inhibiting YAP and promoting pyroptosis. It is speculated that the downregulation of YAP could prevent smoking- and alcohol-induced carcinogenesis in esophageal PCTs by promoting pyroptosis, which may offer new insights for the treatment of esophageal squamous carcinoma.

Gastrointestinal (GI) tumors represent a significant global health burden and are among the leading causes of cancer-related mortality worldwide. their drug resistance is one of the major challenges in cancer therapy. In recent years, epigenetic modifications, especially N6-methyladenosine (m6A) RNA modifications, have become a hot research topic. m6A modification plays an important role in gene expression and cancer progression by regulating RNA splicing, translation, stability, and degradation, which are regulated by "writers," "erasers" and "readers." In GI tumors, resistance to chemotherapy, targeted therapy, and immunotherapy is closely associated with m6A RNA modification. Therefore, the molecular mechanism of m6A modification and its targeted drug development provide new therapeutic strategies for overcoming drug resistance and therapeutic efficacy in GI tumors. In this review, the biological functions of m6A were explored, the specific resistance mechanisms of m6A in different types of GI tumors were explored, new ideas and targets for future treatment resistance were identified, and the limitations of this field were highlighted.

Esophageal squamous cell carcinoma (ESCC) has a high incidence, poor treatment response, and high mortality. Subcutaneous transplant tumor models are commonly used to study the immunosuppressive tumor microenvironment and its impact on immunotherapy. In this study, we established two new ESCC mouse cell lines, mEC525M and mEC586F, from 4NQO-induced ESCC mouse models of different sexes. We compared their proliferation, motility, and molecular characteristics with existing lines (HNM007, AKR, mEC25) using in vitro experiments and whole-exome sequencing. Treatment sensitivity analysis of all murine ESCC tumor cell lines revealed that AKR and HNM007 cells were more responsive to chemotherapy, mEC25 cells were more sensitive to radiotherapy, whereas mEC525M and mEC586F cells exhibited greater sensitivity to immunotherapy. Multiplex immunohistochemistry (mIHC) staining analysis revealed differences in immune infiltration among the tumors derived from the five mouse ESCC cell lines, with the highest proportion of T cells in mEC525M tumors, the highest proportion of CD11b+ myeloid cells in mEC586F tumors and the highest proportion of CD19+ B cells in mEC25 tumors. In addition, RNA sequencing results also revealed differences in immune responses exhibited by tumor tissues derived from the five mouse ESCC cell lines after anti-PD1 treatment. Therefore, this study offers a valuable tool for investigating the immune microenvironment in ESCC and supports the selection of mouse models for preclinical ESCC research.

As a pseudoprotease, RHBDD2 regulates tumor survival and progression in several cancers, but its expression and function in most cancers remain unclear. This study aimed to investigate the role of RHBDD2 in esophageal carcinoma (ESCA) via the use of public datasets and performing cytology experiments and RNA-seq analysis in ESCA cells. RHBDD2 was obviously upregulated and contributed to worse relapse-free survival (RFS) in patients with ESCA. Furthermore, chemotherapy increased RHBDD2 expression, and several GEO datasets also demonstrated that RHBDD2 expression was upregulated in both cisplatin-treated and resistant ESCA cells. Additionally, cytology experiments revealed that cisplatin treatment markedly upregulated the expression of RHBDD2 and γH2AX, which is a DNA damage marker, whereas RHBDD2 knockdown or overexpression affected cisplatin-induced γH2AX expression and the cytotoxic effects of cisplatin. The functional enrichment of RNA-seq data from RHBDD2-knockdown EC9706 cells suggested that RHBDD2-induced DEGs were involved in the DNA damage response and repair. Pearson's correlation analysis revealed that RHBDD2 expression was positively correlated with the expression of several genes, such as DMC1, CBX5, RAD1, DDB2, and ERCC1, which are responsible for DNA damage repair. Taken together, our results first revealed that RHBDD2 is upregulated and responds to DNA damage in ESCA, which provides new evidence for the potential role of RHBDD2 in the chemotherapy sensitivity and survival of patients with ESCA.

Tumor progression in patients with esophageal precancerous lesions (EPLs) or early esophageal carcinoma (EEC) is typically confined in both extent and location. Prompt and effective intervention significantly improves treatment outcomes and prognosis for these individuals.

To determine the effect of endoscopic submucosal dissection (ESD) on efficacy, serum tumor markers (STMs), and 6-month postoperative recurrence rate in patients with either EPL or EEC.

This study initially enrolled 120 patients with EPL or EEC, who were admitted from April 2021 to April 2024. Participants were divided into the control group (60 cases), which underwent thoracotomy, and the research group (60 cases) which received ESD treatment. The comparative analysis involved information regarding the efficacy (dissection area and resection rate per unit time), complications (delayed bleeding, wound infection, esophageal reflux, and postoperative esophageal stenosis), surgery-related parameters (bleeding volume, operation duration, and hospital length of stay), STMs [carcinoembryonic antigen (CEA), carbohydrate antigen 724 (CA724), and tumor-specific growth factor (TSGF)], and the 6-month postoperative recurrence rate of the two groups.

Data indicated statistically higher dissection area and resection rate per unit of time in the research group than in the control group. Meanwhile, the research group demonstrated a notably lower overall incidence rate of complications, bleeding volume, operation duration, and hospital length of stay. Further, the CEA, CA724, and TSGF were markedly reduced in the research group after treatment, which were statistically lower compared to the baseline and those of the control group. Finally, during the follow-up, a comparable 6-month postoperative recurrence rate was determined in the two groups.

ESD is clinically effective and safe for EPL and EEC and can significantly restore abnormally increased levels of STMs.

One of the main characteristics of tumor metabolite reprogramming is enhanced glycolysis, and Pyruvate Kinase M2(PKM2) is a crucial enzyme that limits the pace of glycometabolism. Although PKM2 has been proven to affect the development of some cancers, a pan-cancer analysis of PKM2 has not yet been performed. We analyzed the expression and prognosis of PKM2 in pan-cancer using multiple databases. We performed epigenetic, functional enrichment, immune cell infiltration, immune checkpoint, and drug sensitivity analyses of PKM2. PKM2 was found to be significantly upregulated in most malignancies and associated with a bad prognosis. In some cancers, the PKM2 DNA promoter was hypomethylated. The expression of PKM2 was positively linked with most m6A-methylation-related genes in pan-cancer. The functions of PKM2 were primarily associated with the regulation of the immune system, glycolysis, hypoxia, angiogenesis, and epithelial-mesenchymal transition. PKM2 was favorably associated with neutrophils and cancer-associated fibroblasts in the tumor microenvironment of most cancers. Importantly, PKM2 showed a strikingly high correlation with CD274 (PD-L1), CD276, TGF-β1, VEGFA, and HAVCR2 in most cancers. Finally, using experiments, it was confirmed that silencing PKM2 could increase the sensitivity of esophageal squamous cell carcinoma to cisplatin by regulating autophagy. PKM2 affects autophagy - regulated tumor cell tolerance to chemotherapy, providing future research directions for solving tumor chemotherapy resistance.

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies, characterized by high heterogeneity and poor outcomes. Effective classification for patient stratification and identifying reliable markers for prognosis prediction and treatment choice are crucial.

Integration of single-cell RNA-sequencing (RNA-seq) and bulk RNA-seq analyses were used to characterize ESCC. Non-negative matrix factorization (NMF) clustering was performed to stratify the ESCC patients into different subtypes and the clinical and pathological features of the ESCC subtypes were compared. Cox regression analysis and LASSO regression analysis were used to select key genes and construct a risk model for ESCC. The associations of the key genes with anti-cancer drug sensitivities in ESCC cell lines were investigated. RT-qRCR experiments, proteomics analysis, and multiplex immunohistochemistry (mIHC) experiments were used to validate the results. Furthermore, one identified gene was selected to investigate its correlation with EGFR expression and the gene effect scores of various potential gene targets across pan-cancer.

The study identified the dysregulated distributions of epithelial cells and fibroblasts as characteristic of ESCC. ESCC patients could be classified into four distinct subtypes with unique cell type features and prognoses. With the gene makers of the cell type features, a four-gene prognostic signature for ESCC was constructed. The CCND1-PKP1-JUP-ANKRD12 model could effectively discriminate the survival status of ESCC patients, independent of various pathological and clinical features. The risk score for the samples was correlated with the expression levels of immunoregulatory genes. The prognostic effects of CCND1, PKP1, and JUP were confirmed at the protein level. The phosphorylation levels of PKP1, JUP, and ANKRD12 were found to be dysregulated in ESCC tumors. Their expression dysregulation and heterogeneity were demonstrated in ESCC cell lines. All four genes were significantly correlated with at least one of the anti-cancer drug sensitivities in ESCC cell lines. PKP1 expression was significantly correlated with EGFR expression and gene effect scores in multiple cancers.

We conclude that the CCND1-PKP1-JUP-ANKRD12 signature may serve as a novel indicator for ESCC prognosis and diagnosis. PKP1 expression might provide new clues for gene therapy efficacy in multiple cancers.

Programmed cell death protein-1 (PD-1) blockade has improved survival for patients with esophageal squamous cell carcinoma (ESCC), but response rates are low. Biomarkers to predict who will benefit from PD-1 blockade are urgently needed.

This multicenter study involved 250 patients with recurrent/unresectable advanced ESCC receiving nivolumab as second- or later-line therapy. We assessed tumor-infiltrating T lymphocytes (TILs) and tertiary lymphoid structure (TLS) density using immunohistochemistry and hematoxylin/eosin staining in surgical specimens and pre-nivolumab endoscopic biopsies.

In surgical specimens, clinical response (vs. non-response) to nivolumab correlated significantly with CD8+ lymphocyte count (160 vs. 95.2 cells/field, P = 0.0494), CD8/Foxp3 ratio (6.52 vs. 2.72, P = 0.0053), and TLS density (0.21/mm2 vs. 0.10/mm2, P = 0.0005). In terms of overall survival, multivariate analysis identified CD8/Foxp3 ratio (hazard ratio [HR] = 1.83, P = 0.0050) and TLS density (HR = 1.67, P = 0.0171 as independent prognostic parameters in surgical specimens. Similarly, in endoscopic biopsies, clinical response (vs. non-response) to nivolumab correlated significantly with CD8+ counts (254 cells/mm2 vs. 124 cells/mm2, P = 0.0344), CCR8+ lymphocyte count (62.6 cells/mm2 vs. 140 cells/mm2, P = 0.0355), CD8/Foxp3 ratio (2.09 vs. 0.89, P = 0.040), and CD8/CCR8 ratio (2.34 vs. 0.89, P = 0.0020). Multivariate analysis also identified CD8/CCR8 ratio in endoscopic biopsies (HR = 1.66, P = 0.0313) as an independent prognostic parameter.

CD8+ and CCR8+ cell counts, CD8/Foxp3 and CD8/CCR8 ratios, and TLS density may be predictive biomarkers of therapeutic efficacy and survival with PD-1 blockade for ESCC.

This study aimed to delineate the evolving knowledge structure of programmed cell death in esophageal cancer and identify key thematic trends, influential collaborations, and emerging areas for future research.

A bibliometric approach was applied to 2677 publications retrieved from the Web of Science Core Collection (2000-2024). Three complementary tools-CiteSpace, VOSviewer, and bibliometrix-were employed to visualize co-citation networks, detect citation bursts, and map collaborative patterns among authors, institutions, and countries. Inclusion criteria focused on articles and reviews that addressed esophageal cancer in conjunction with apoptosis, necroptosis, pyroptosis, ferroptosis, autophagy, or related pathways.

Publication outputs grew markedly, reflecting a shift from early investigations of basic apoptotic mechanisms to broader explorations of necroptosis, pyroptosis, and ferroptosis. China led in publication volume and citations, driven by substantial governmental funding and large clinical cohorts. The United States and Japan also contributed significantly, forming international research networks that spanned Asia and Europe. Leading institutions, particularly Zhengzhou University, demonstrated extensive collaborations. Journals such as Oncology Letters and Oncology Reports were prominent outlets for new findings, while highly cited references highlighted hypoxia, immune checkpoint blockade, and emerging gene-editing strategies. Keyword analyses revealed the ascendance of immuno-oncology, network pharmacology, and translational applications targeting multiple regulated cell death pathways.

Bibliometric evidence underscores a rapid expansion of multidisciplinary research that integrates diverse cell death pathways in esophageal cancer. Continued international collaborations, leveraging advanced genomics and immunologic strategies, are poised to accelerate translational breakthroughs and enable more personalized, effective therapies.

Esophageal cancer (EC) remains highly lethal due to tumor microenvironment (TME)-mediated immune evasion. While natural killer (NK) cells are central to antitumor immunity, their functional states in EC are poorly characterized.

We integrated bulk RNA-seq (TCGA/GEO) and single-cell data to construct an NK cell-derived prognostic signature (NK score) via LASSO-Cox regression. Immunofluorescence was applied to assess the clinical relevance of SAMD3 + NK cells in EC. Using both xenograft mouse models and in vitro co-culture procedures, the impact of SAMD3 on NK cell function was confirmed.

In EC patients, the prognostic NK score-which is generated from important NK cell markers including SAMD3-was substantially correlated with a worse chance of survival. NK cells within the TME had significant levels of SAMD3 expression, as seen by immunofluorescence labeling. Moreover, NK cells with SAMD3 knockdown exhibited enhanced antitumor activity, leading to decreased tumor development in the xenograft model.

Our results demonstrate the predictive significance of NK cell markers in EC and pinpoint SAMD3 as a critical modulator of NK cell activity. We pioneer SAMD3 + NK cells as architects of TME immunosuppression in EC. Our findings nominate SAMD3 inhibition as a combinatorial strategy to overcome immune checkpoint blockade resistance.

Our study aims to identify the molecular subtypes of genes associated with disulfidptosis in esophageal squamous cell carcinoma(ESCC), develop a prognostic model, and identify potential therapeutic targets.

Based on the GSE53625 expression profile data, we identified molecular subtypes with significant survival differences through consensus cluster analysis. Subsequently, univariate Cox, multivariate Cox, and LASSO-Cox regression analysis were used to establish risk stratification models. The transcriptome data of the TCGA-ESCC cohort and the GSE160269 single-cell sequencing dataset were integrated to verify the biological significance of the model, and further analyze the heterogeneity of the tumor immune microenvironment, explore the differences in the intercellular communication network, and screen potential targeted drugs, providing a theoretical basis for subsequent translational research.

We identified two distinct patterns of disulfidptosis expression with significant differences in overall survival. Then, we constructed the prognostic signature of disulfidptosis, and results showed patients with high score had worse prognosis. Univariate and multivariate Cox analysis demonstrated that the constructed prognostic signature was an independent prognostic factor and was validated in an independent validation set. The two subgroups differed in the proportion of immune cell infiltration and related signaling pathways in ESCC. The exploration of immunotherapy data confirmed our prognostic signature also had certain predictive power for immunotherapy. Drug screening suggested AZD8186 and JQ1 as potential therapies for high-score patients.

This study provides a new prognostic signature for ESCC, explores new therapeutic targets, and provides new theoretical support for personalized treatment.