Esophageal Squamous Cell Carcinoma Research Articles

Associations between colonization with Helicobacter pylori and risk of gastrointestinal tract cancers: An umbrella review of meta-analyses.

Several studies have investigated the association between Helicobacter pylori colonization and gastrointestinal malignancies. However, inconsistent results have been found, leaving no clear consensus. Umbrella review of meta-analyses of observational studies aiming to understand the association between Helicobacter pylori colonization and gastrointestinal cancers in humans. MEDLINE, the Cochrane Library of Systematic Reviews, EMBASE, Scopus and Google Scholar were searched from their inception to January 2025. Quality assessment was performed with the AMSTAR 2 tool. The study was registered on PROSPERO (CRD42024523832). Of 1320 records, 38 meta-analyses were included, investigating biliary tract, colorectal, oesophageal, gastric, liver and pancreatic cancers. After dealing with primary study overlap and updating meta-analyses with over 160 studies, Helicobacter pylori was positively associated with biliary tract [OR 2.67 (1.57-4.52)], colorectal [OR 1.40 (1.23-1.60)], gastric [OR 2.10 (1.34-3.31)], liver [OR 5.13 (3.14-8.38)] and pancreatic [OR 1.24 (1.04-1.48)] cancers, while oesophageal adenocarcinoma (EAC) was inversely associated with it [OR .58 (.46-.72)]. The cytotoxic-associated gene A (CagA) protein was positively associated with biliary [OR 2.19 (1.07-4.50)], colorectal [OR 2.04 (1.47-2.82)], oesophageal squamous cell carcinoma [OR 1.56 (1.30-1.89)] and gastric cancers [OR 2.53 (1.94-3.30)], and inversely associated with EAC [OR .60 (.44-.81)] and pancreatic [OR .85 (.75-.97)] cancers. Our results sprout from mostly critically low-quality meta-analyses and moderate to high quality primary studies. Exposure to Helicobacter pylori colonization and its proteins is associated with not only gastric cancer, but also other GI tract cancers. Directionally different results may be seen when specific virulence factors/organ sites are investigated.

Nomogram based on a novel nutritional immune-inflammatory status score to predict postoperative outcomes in esophageal squamous cell carcinoma.

The relationship between patient nutritional, immune, and inflammatory status is linked to tumor progression and prognosis. However, there are limited studies on the prognosis of esophageal squamous cell carcinoma (ESCC) after surgery based on the comprehensive indicators of these factors. To develop and validate a novel nomogram based on a nutritional immune-inflammatory status (NIIS) score for predicting postoperative outcomes in ESCC. This retrospective study examined 829 patients with ESCC who underwent radical surgery between June 2016 and June 2020, with 568 patients in the training cohort and 261 patients in the validation cohort. We incorporated comprehensive indicators related to nutrition, immunity, and inflammation to develop the NIIS score, using LASSO regression. Subsequently, a nomogram combining the NIIS score and other clinicopathological parameters was developed and validated using calibration curves, time-dependent area under curves, and decision curve analysis. We identified eight indicators that constitute the NIIS score. High-risk scores emerged as an independent risk factor for overall survival [training set HR 2.497 (1.802, 3.458), P < 0.001]. A NIIS nomogram for personalized prognostic prediction was developed by integrating the NIIS score with clinicopathological variables, yielding enhanced predictive value relative to individual indicators and the UICC/TNM staging system. The NIIS score provides strong predictive value for postoperative outcomes in ESCC, thus offering a valuable tool for clinical decision-making.

High expression of tetraspanin CD63 predicts poor prognosis in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) has one of the poorest cancer prognosis rates; there is an urgent need to develop new drug therapies and biomarkers. CD63, a tetraspanin protein and well-known exosomal marker, is implicated in cancer progression; however, the significance of CD63 expression in ESCC remains unclear. Herein, we report the significance of CD63 expression by analyzing ESCC patient samples and ESCC cell lines. ESCC patient samples (n=86) were evaluated for CD63 expression by immunostaining; univariate and multivariate analysis using Cox proportional hazards were used to evaluate CD63 expression and clinicopathological features as prognostic factors for survival. For in vitro analysis, CD63 knockdown was performed in human ESCC cell lines (TE2 and TE15) using siRNA, and changes in proliferative potential. The gene expression change were also analyzed by microarray and gene set enrichment analysis. Overall survival was significantly worse in the CD63 high group (P=0.031, log-rank test). Five-year overall survival univariate analysis identified positive lymph nodes, pStage 3 or higher, and CD63 high expression as poor prognostic factors, while multivariate analysis showed that CD63 high expression was an independent poor prognostic factor (P=0.009, HR 2.56, 95%CI 1.269-5.167). CD63 knockdown in ESCC cell lines resulted in a phenotype of decreased proliferative potential. CD63 knockdown increased the expression of genes involved in cell adhesion and suppressed the expression of genes involved in granule secretion. CD63 also shown to affect nuclear import, protein complex localization, and ERBB-signaling pathways. In conclusion, CD63 affects gene expression in ESCC, and high tissue expression of CD63 predicts poor prognosis in ESCC patients.

Absolute risk prediction for esophageal squamous cell carcinoma adaptable to regional disease burden across diverse regions.

Esophageal squamous cell carcinoma (ESCC) exhibits a long latency period and has a significant geographical disparity in incidence, which underscores the need for models predicting the long-term absolute risk adaptable to regional disease burden. 31,883 participants in a large-scale population-based screening trial (Hua County, China) were enrolled to develop the model. Severe dysplasia and above (SDA) identified at screening or follow-up were defined as the outcome. We calculated the absolute risk in three steps: 1) constructing a relative risk model using logistic regression, 2) calculating the age-specific baseline hazard, and 3) adjusting for the competing risk of all-cause death excluding ESCC. Flexible incidence rate parameters were integrated into the model to ensure its relevance across diverse regions worldwide. A total of 295 SDAs were detected. The relative risk model consisted of old age, male gender, irregular meal pattern, preference for hot or hard food, BMI of less than 22 kg/m2, and ESCC family history. The area under the receiver operating characteristic curve was 0.753 (95% CI: 0.749-0.757). The averaged 5-year and 10-year absolute risk were 0.53% and 1.30% among participants. Based on our model, we developed an online calculator incorporated flexible incidence rate parameters, demonstrating ideal risk stratification tailored to regions with varying disease burdens (https://pkugenetics.shinyapps.io/escc_risk_prediction/). We developed an absolute risk model to predict individualized long-term risk of ESCC, accounting for local disease burden. This model has the potential to mitigate the global burden of ESCC by enabling targeted screening and personalized prevention strategies.

A panel of cancer testis antigens in squamous cell carcinoma of the lung, head and neck, and esophagus: implication for biomarkers and therapeutic targets

This study aims to investigate the expression of seven cancer testis antigens (MAGE-A1, MAGE-A4, MAGE-A10, MAGE-A11, PRAME, NY-ESO-1 and KK-LC-1) in pan squamous cell carcinoma and their prognostic value, thus assessing the potential of these CTAs as immunotherapeutic targets. The protein expression of these CTAs was evaluated by immunohistochemistry in 60 lung squamous cell carcinoma (LUSC), 62 esophageal squamous cell carcinoma (ESCA) and 62 head and neck squamous cell carcinoma (HNSC). The relationship between CTAs expression and progression-free survival (PFS) was assessed. PD-L1 expression and tumor-infiltrating lymphocytes were also collected and correlated with CTAs expression. The prognostic impact of CTAs gene expression was evaluated using the Kaplan–Meier Plotter website. CTAs expression was 0–48% in ESCA, 3%-77% in LUSC, and 3%-71% in HNSC. Analysis of PFS showed that MAGE-A1 expression in HNSC (**p < 0.01), PRAME in LUSC (p = 0.008, **p < 0.01), MAGE-A10 (p = 0.012, *p < 0.05) and PRAME (p = 0.021, *p < 0.05) in ESCA were significantly correlated with PFS. In all three cancers, coexpression of three CTAs was used as a cutoff value for grouping, and the results showed a significant difference in PFS between these two groups. Moreover, CTAs expression was significantly correlated with PD-L1 expression and T cell infiltration. These findings indicate a high incidence of CTA expression in HNSC, LUSC and ESCA, which was correlated with PD-L1 expression, T cell infiltration, and tumor progression. The results suggest that cancer testis antigens could be feasible vaccine targets in squamous cell carcinoma.

Right versus left thoracic approach esophagectomy for patients with neoadjuvant immunochemotherapy

Background The purpose of this study was to investigate the safety and efficacy of left thoracic approach (LTA) and right thoracic approach (RTA) in patients with esophageal squamous cell carcinoma (ESCC) after neoadjuvant immunochemotherapy (NICT). Methods This study included 83 ESCC patients who underwent right transthoracic esophagectomy (n = 61) and left transthoracic esophagectomy (n = 22) after NICT in our hospital from October 2019 to September 2023. The data of these patients were retrospectively analyzed. Results Compared with the LTA group, the RTA group had a longer operation time (245.6 ± 27.8 min vs. 356.5 ± 83.2 min, p < 0.001) and more lymph nodes were removed (21.0 ± 7.9 vs. 29.3 ± 10.8, p = 0.001). The 3-year disease free survival (DFS) of the LTA group and the RTA group were 61.0% and 65.7% (p = 0.861), and the 3-year overall survival (OS) were 60.7% and 77.4% (p = 0.753) respectively. There was no significant difference in prognosis between the two groups. Lymphovascular invasion was an independent risk factor for DFS (HR = 4.042, p = 0.004) and OS (HR = 4.607, p = 0.003) in patients with ESCC undergoing NICT combined with surgery. Conclusion There was no difference in postoperative complications and short-term survival in patients with ESCC underwent surgery after NICT regardless of left or right thoracic approach. It is worth noting that lymphovascular invasion has an important impact on the prognosis of these patients.

Exploring novel immunotherapy in advanced esophageal squamous cell carcinoma: Is targeting TIGIT an answer?

Esophageal squamous cell carcinoma (ESCC) is a prevalent and highly lethal malignancy in Asia. Recent advancements in immune checkpoint inhibitors (ICIs) have markedly transformed the systemic therapy landscape for ESCC. Anti-PD-1-based combination with chemotherapy or with ipilimumab, an anti-CTLA-4 antibody, have been established as the new standard first-line treatments for patients with advanced ESCC. Moreover, anti-PD-1 monotherapy has demonstrated improved efficacy and survival compared with second-line chemotherapy in previously treated patients with ESCC. Novel ICIs targeting other immune checkpoints also show potential for enhancing anticancer therapy in advanced ESCC.The TIGIT/PVR pathway represents a new immune checkpoint. Preclinical studies have indicated that the dual blockade of TIGIT and PD-1 can enhance antitumor immune responses. Clinical trials have reported that combining anti-TIGIT with anti-PD-1/PD-L1 antibodies elicited clinical responses in patients with advanced ESCC. In the first-line systemic therapy setting, combinations of dual ICIs targeting TIGIT and PD-1/PD-L1 plus platinum-based chemotherapy have demonstrated acceptable toxicity profiles and promising antitumor activity in several phase II trials and one phase III study. However, the role of adding an anti-TIGIT antibody to the current standard of anti-PD-1/PD-L1 plus platinum-based chemotherapy in first-line therapy for advanced ESCC remains to be fully determined, necessitating further clinical trials. Ongoing studies are also investigating the role of anti-TIGIT, with or without anti-PD-1/PD-L1, in locoregional ESCC. Additional research is essential to optimize the potential of anti-TIGIT therapy in ESCC and other malignancies by identifying predictive biomarkers, determining optimal antibody types, and gaining key mechanistic insights.

Association between serum levels of 12 different cytokines and short-term efficacy of chemoradiotherapy in esophageal squamous cell carcinoma

BackgroundEsophageal squamous cell carcinoma (ESCC) has a poor prognosis, with chemoradiotherapy (CRT) being a key treatment method. This study focused on circulating cytokines as potential predictors of treatment response and prognosis in patients with ESCC.Materials and methodsSerum samples were collected from 36 ESCC patients, and 12 different cytokines were quantified using a multiplex immunofluorescence assay. We used non-parametric Wilcoxon unpaired rank tests to examine the relationship between cytokine concentrations and clinical outcomes. The duration of progression-free survival was assessed through imaging studies and telephone follow-ups. Kaplan–Meier survival plots, analyzed with the log-rank test, were utilized to depict survival trends.ResultsPre-treatment serum IL-8 levels were significantly elevated in patients with lymphoid metastases (p = 0.036). Lower initial levels of IL-8 and IL-1β were observed in patients with partial response group compared to those with stable disease (p = 0.002, p = 0.01). Elevated baseline levels of IL-8 and interferon-gamma (IFN-γ) were correlated with a poorer prognosis. Higher levels of IL-5 and IFN-γ levels following therapy were associated with worse outcomes.ConclusionsOur findings indicate that IL-8, IL-1β, IL-5, and IFN-γ may serve as potential biomarkers for treatment efficacy and prognosis in ESCC. Patients with low levels of IL-8 and IL-1β demonstrate a favorable response to CRT. Elevated serum levels of IL-8, IL-1β, IFN-γ, and IL-5 may predict poorer clinical outcomes.

Status and prospect of esophageal cancer screening

Esophageal cancer is one of the global public health problems, which is a serious threat to life and health. Screening is not only an important main measures to reduce the incidence and mortality of esophageal cancer, but also an effective strategy for early prevention and early treatment. There are significant differences in the screening status of esophageal adenocarcinoma and esophageal squamous cell carcinoma cancer between China and abroad. Internationally, there are several guidelines for screening and monitoring of Barrett's esophagus and esophageal adenocarcinoma, but most guidelines do not recommend screening in the general population. The primary screening by sponge ball then endoscopic diagnosis is a new focus. In China, the screening of esophageal cancer and its precancerous lesions is mainly esophageal squamous cell carcinoma, which has been relatively mature and gradually transformed from population screening to opportunistic screening. However, due to the high cost, high technical difficulty and certain invasiveness, it is difficult to popularize and be applied widely; and the canceration rate of precancerous lesions is low, so it is very important to control the cost of screening and scientific follow-up. Moreover, high-risk population should raise their awareness of cancer prevention, actively take primary prevention and the initiative to participate in screening. About medicine institutions, it is urgent to improve the awareness and capacity of early screening. The multi-disciplinary research cooperation, minimally invasive, simple and economical screening methods and multi-omics biomarkers are still explored to detect and concentrate high-risk populations, which will help to optimize screening programs of esophageal cancer and further reduce the incidence and mortality of esophageal cancer.

Optimal treatment strategy for older patients with esophageal squamous cell carcinoma: A multicenter retrospective study

Optimal treatment strategy for older patients with esophageal squamous cell carcinoma: A multicenter retrospective study

The impact of radiation-related lymphocyte recovery on the prognosis of locally advanced esophageal squamous cell carcinoma patients: a retrospective analysis

BackgroundThe impact of radiation-related lymphocyte recovery on prognosis in locally advanced esophageal squamous cell carcinoma (LA-ESCC) remains unclear.MethodsPatients with stage II-IVa ESCC who received definitive RT were screened. Collect absolute lymphocyte counts (ALCs) before, during, and after RT. The recovery status of lymphocytes was observed at one-month post-RT (P1) and three months post-RT (P3). Patients with relatively lower lymphocyte recovery levels at P1 were divided into Group a and those with higher levels were divided into Group b. Patients with relatively lower lymphocyte recovery levels at P3 were divided into Group A and those higher were divided into Group B. Kaplan-Merier’s analysis and Cox analysis were conducted to compare survival outcomes. Binary logistic regression analyses was employed to ascertain factors associated with lymphocyte recovery.Results116 patients were enrolled. During RT, ALCs reached the bottom 5 weeks after RT started and 70.7% of patients experienced G3 lymphopenia. The median OS for Group a and Group b were 38.1 months and 14.4 months, p = 0.097. The median PFS for Group a and Group b were 14.2 months and 10.0 months, p = 0.037. Whereas, the median OS for Group A and Group B was 14.5 months and 22.2 months, p = 0.019. The median PFS for Group A and Group B were 8.4 months and 12.4 months, p = 0.021. Cox multivariable analysis revealed that higher lymphocyte recovery level at P3 was significantly associated with superior OS (p = 0.040, HR0.636) and PFS (p = 0.028, HR0.627). The logistic analysis identified a positive association between G4 lymphopenia during RT (p = 0.012, OR 7.742) and PTV dose < 60 Gy (p = 0.014, OR 2.655) with lymphocyte recovery.ConclusionsThe prognostic value of lymphocyte recovery status at P3 appears to be greater than that of lymphocyte recovery status at P1 for locally advanced ESCC patients. Radiation-related lymphocyte recovery might serve as a valuable prognostic factor in LA-ESCC.

Development a glycosylated extracellular vesicle-derived miRNA Signature for early detection of esophageal squamous cell carcinoma

BackgroundEsophageal squamous cell carcinoma (ESCC) is often diagnosed at an advanced stage due to the lack of non-invasive early detection tools, which significantly impacts patient prognosis. Given that glycosylation alterations especially high sialylation and fucosylation, frequently occur during cellular malignant transformation, but their roles are not elucidated. We examined alterations in disease-specific glycosylated extracellular vesicles (EVs)-derived miRNAs in the serum of ESCC patients, evaluating their utility as diagnostic biomarkers.MethodsA total of 371 ESCC and 303 healthy controls (HCs) were recruited in this multi-stage, multicentre case-control study. Fucosylated (Fuc-) and sialylated (Sia-) EVs were isolated utilizing Lentil lectin (LCA) and wheat germ lectin (WGA)-coated magnetic beads, respectively. The glycosylated EVs-derived miRNAs-based signature (RiskscoreFuc−&Sia−) was established through logistic regression in a training cohort and subsequently validated in an internal and an external multicentre cohort.ResultsThe RiskscoreFuc−&Sia− effectively identified ESCC across all stages, demonstrating high AUC values in training (0.980), internal validation (0.957), and external multicentre validation (0.973) cohorts, markedly higher than carcinoembryonic antigen (CEA) (AUC = 0.769, training cohort; AUC = 0.749, internal validation cohort; AUC = 0.765, external validation cohort). Notably, this score exhibited robust accuracy in detecting CEA (-) ESCC cases (CEA < 5 ng/ml) (AUC = 0.974, training & internal cohort; AUC = 0.973, external multicentre validation cohort). Additionally, it displayed strong efficacy in differentiating early-stage ESCC patients (AUC = 0.982, training cohort; AUC = 0.977, external multicentre validation cohort).ConclusionsOur study illustrates the effectiveness of glycosylated EVs capture strategy for isolating tumour-specific EVs. The unique glycosylated EVs-derived miRNAs-based signature shows the optimal potential as a biomarker for early detection of ESCC.Graphical

Association between dietary antioxidants, serum albumin/globulin ratio and quality of life in esophageal squamous cell carcinoma patients: a 7-year follow-up study

Association between dietary antioxidants, serum albumin/globulin ratio and quality of life in esophageal squamous cell carcinoma patients: a 7-year follow-up study

Development and validation of a novel artificial intelligence algorithm for precise prediction the postoperative prognosis of esophageal squamous cell carcinoma

BackgroundEsophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy, and current postoperative prognostic assessment methods remain unsatisfactory, underlining the urgent to develop a reliable approach for precision medicine. Given the similarities with gametogenesis, cancer/testis genes (CTGs) are acknowledged for regulation unrestrained multiplication and immune microenvironment during oncogenic processes. These processes are associated with advanced disease and poorer prognosis, indicating that CTGs could serve as ideal prognostic biomarkers in ESCC. The purpose of this study is to develop a novel clinically prognostic prediction system to facilitate the individualized postoperative care.MethodsWe conducted LASSO regression analysis of protein-coding CTGs and clinical characteristics from 119 pathologically confirmed ESCC patients to recognize powerful predictive variables. We employed nine supervised machine learning classifiers and integrated best predictive machine learning classifiers by weighted voting method to construct an ensemble model called PPMESCC. Additionally, functional assay was conducted to examine the potential effect of top-ranking CTG HENMT1 in ESCC.ResultsLASSO regression identified five CTGs and TNM stage as optimized prognostic features. Six machine learning classifiers were integrated to construct an ensemble model, PPMESCC, which exhibited outstanding performance in ESCC prediction. The AUC for PPMESCC was 0.9828 (95% confidence interval: 0.9608 to 0.9926), with an accuracy of 98.32% (95% CI: 96.64–99.16%) in the discovery cohort and 0.9057 (95% CI: 0.8897 to 0.9583) of AUC with an accuracy of 90% (95% CI: 89.08–93.28%) in validation cohort. In addition, the top-ranking CTG HENMT1 encodes 2’-O-methyltransferase of piRNAs that was confirmed positively correlated with the proliferation capacity of ESCC cells. Then we systematically screen piRNAs associated with esophageal carcinoma based on GWAS, eQTL-piRNA, and i2OM databases, and successfully discovered 8 piRNAs potentially regulated by HENMT1.ConclusionThe study highlights the clinical utility of PPMESCC algorithm in prognostic prediction that may facilitate to establish the personalized screening and management strategies for postoperative ESCC patients.

SUMO-Specific Peptidase 5 Promotes Oesophageal Squamous Cell Carcinoma Growth through the NF-κB-SLC1A3 Axis.

This study investigates the role of small ubiquitin-like modifier (SUMO)-specific peptidase 5 (SENP5), a key regulator of SUMOylation, in esophageal squamous cell carcinoma (ESCC), a lethal disease, and its underlying molecular mechanisms. Differentially expressed genes between ESCC mouse oesophageal cancer tissues and normal tissues were analysed via RNA-seq; among them, SENP5 expression was upregulated, and this gene was selected for further analysis. Immunohistochemistry and western blotting were then used to validate the increased protein level of SENP5 in both mouse and human ESCC samples. The Kaplan‒Meier method and multivariate analysis were used to analyse the relationship between SENP5 expression and ESCC prognosis. Stable SENP5-knockdown (KD) cell lines and conditional knockout (cKO) mice were established to verify the biological function of SENP5. Further RNA-seq comparisons between short hairpin SENP5 (shSENP5)- and short hairpin negative control (shNC)-transfected ESCC cell lines were conducted, and the nuclear factor kappa B (NF-κB)-SLC1A3 axis was identified through bioinformatics analysis. The correlation of SENP5 with signalling pathway components was validated via real-time quantitative PCR (qPCR), western blotting (WB), and immunoprecipitation. Our study revealed that SENP5 was upregulated in human and mouse ESCC samples, and clinical data analysis revealed a correlation between high SENP5 expression and poor patient prognosis. SENP5 knockdown inhibited tumorigenesis and growth in vivo and suppressed the proliferation, migration, and invasion of ESCC cell lines in vitro. Our study also revealed that SENP5 knockdown enhanced the SUMO1-mediated SUMOylation of NF-kappa-B inhibitor alpha (IκBα), thereby inhibiting the activation of the NF-κB-SLC1A3 axis, which subsequently suppresses ESCC cell energy metabolism and impedes ESCC progression. Suppression of SENP5 slows the development of ESCC by inhibiting the NF-κB‒SLC1A3 axis through SUMO1-mediated SUMOylation of IκBα. Our research suggests that SENP5 could serve as a prognostic indicator and a target for therapeutic intervention for ESCC patients.

The necroptosis-related lncRNA ENSG00000253385.1 promotes the progression of esophageal squamous cell carcinoma by targeting the miR-16-2-3p/VDAC1 axis

Esophageal squamous cell carcinoma (ESCC) is one of the most common digestive malignancies. Our previous studies revealed necroptosis-related lncRNA ENSG00000253385.1 was an independent prognostic factor for ESCC. However, the specific regulatory mechanisms are unknown. This study aimed to investigate the expression of the lncRNA ENSG00000253385.1 in ESCC tissues and its relationship with clinicopathological features and patient prognosis, and to explore its potential regulatory mechanism in ESCC cells. We detected the location of the lncRNA ENSG00000253385.1 in ESCC cells by fluorescence in situ hybridization (FISH). FISH and quantitative real-time polymerase chain reaction (qRT‒PCR) were used to detect gene expression in ESCC tissues and cells. Cell proliferation, migration and apoptosis were evaluated by CCK-8 assay, wound healing, transwell cell migration, invasion and flow cytometry assay. The levels of necroptosis-related protein were detected by western blot. The binding sites between miR-16-2-3p and lncRNA ENSG00000253385.1 or voltage-dependent anion channel 1 (VDAC1) were predicted by bioinformatics database and confirmed by dual luciferase reporter gene assay. Results revealed that the lncRNA ENSG00000253385.1 expression was higher in ESCC tissues than in the adjacent tissues. High lncRNA ENSG00000253385.1 expression, positive lymph node metastasis and clinical stage III were associated with poor overall survival (OS) in patients with ESCC, and were independent risk factors for prognosis of patients with ESCC. The lncRNA ENSG00000253385.1 was located in the cytoplasm. MiR-16-2-3p had a direct targeting regulatory relation ship with lncRNA ENSG00000253385.1 and VDAC1. MiR-16-2-3p inhibitor promoted proliferation, migration and invasion, and inhibited apoptosis of ESCC cells. Knockdown of the lncRNA ENSG00000253385.1 could inhibit the proliferation, migration and invasion, promote the apoptosis, and result in increases in the necroptosis-related proteins p-receptor-interacting protein kinase 3 (RIPK3)/RIPK3 and p-mixed lineaae kinase domain-like protein (MLKL)/MLKL and a decrease in the VDAC1 protein levels in ESCC cells, whereas miR-16-2-3p inhibition rescued these effects. Therefore, The lncRNA ENSG00000253385.1/ miR-16-2-3p/VDAC1 axis may be considered as a potential predictive biomarker and target for ESCC.

Clinical value of preoperative circulating tumor DNA before surgery in patients with esophageal squamous cell carcinoma.

A precise preoperative tumor monitoring method that reflects tumor burden during neoadjuvant treatment is required to guide individualized perioperative treatment strategies for esophageal squamous cell carcinoma (ESCC). This study examined the clinical significance of preoperative circulating tumor DNA (ctDNA) in the plasma of patients undergoing neoadjuvant chemotherapy (NAC) followed by esophagectomy. Plasma samples were collected longitudinally for ctDNA analysis as well as genomic DNA from primary lesions from patients with histologically confirmed ESCC who received neoadjuvant chemotherapy (NAC) followed by subtotal esophagectomy. Next-generation sequencing was used to identify mutations in both the plasma and primary tumors. We evaluated the relationship between ctDNA alterations and recurrence in patients with locally advanced ESCC. Pretreatment samples from 25 patients (100%) showed the same mutations in both ctDNA and primary tumors; therefore, they were classified as ctDNA-positive before treatment. In the cohort of 25 patients analyzed, those who tested positive for ctDNA after NAC had a significantly higher risk of recurrence; the 36-month recurrence-free survival rates were 92% for ctDNA-negative patients and 8% for ctDNA-positive patients (p<0.001). Preoperative ctDNA status may be a promising prognostic biomarker that can be assessed before surgery in patients with ESCC who received NAC. Expanded cohort validation will allow for more personalized multidisciplinary treatment approaches for ESCC tailored to ctDNA analysis.

Vasculogenic mimicry and p53 expression in esophageal squamous cell carcinoma patients of Kazakh ethnicity, the association between vasculogenic mimicry and p53 expression and its influence on prognosis

Vasculogenic mimicry and p53 expression in esophageal squamous cell carcinoma patients of Kazakh ethnicity, the association between vasculogenic mimicry and p53 expression and its influence on prognosis

Letetresgene Autoleucel in Advanced/Metastatic Myxoid/Round Cell Liposarcoma.

The cancer/testis antigen New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a promising target in myxoid/round cell liposarcoma (MRCLS). In this pilot study, we assessed the adoptive T-cell therapy NY-ESO-1c259T letetresgene autoleucel (lete-cel) in patients with human leukocyte antigen (HLA)-A*02:01-, HLA-A*02:05-, and/or HLA-A*02:06-positive advanced/metastatic NY-ESO-1-expressing MRCLS. Patients underwent a reduced-dose (cohort 1) or standard-dose (cohort 2) lymphodepletion regimen (LDR). The primary end point was investigator-assessed overall response rate (ORR). Safety was assessed through adverse event (AE) reports. Correlative biomarker analyses were performed post hoc. The trial is registered at ClinicalTrials.gov (identifier: NCT02992743). Of 23 enrolled patients, 10 in cohort 1 and 10 in cohort 2 received lete-cel. Investigator-assessed ORR was 20% (95% CI, 2.5 to 55.6) and 40% (95% CI, 12.2 to 73.8), median duration of response was 5.3 months (95% CI, 1.9 to 8.7) and 7.5 months (95% CI, 6.0 to not estimable [NE]), and median progression-free survival was 5.4 months (95% CI, 2.0 to 11.5) and 8.7 months (95% CI, 0.9 to NE) in cohorts 1 and 2, respectively. AEs included cytokine release syndrome and cytopenias, consistent with T-cell therapy/LDR. Post hoc correlative biomarkers showed T-cell expansion and persistence in both cohorts. To our knowledge, this study is the first demonstrating the clinical promise of lete-cel in HLA-/NY-ESO-1-positive patients with advanced MRCLS.

Revolutionizing ESCC prognosis: the efficiency of tumor-infiltrating immune cells (TIIC) signature score

BackgroundPatients suffer from esophageal squamous cell carcinoma (ESCC), which is the ninth highly aggressive malignancy. Tumor-infiltrating immune cells (TIIC) exert as major component of the tumor microenvironment (TME), showing possible prognostic value in ESCC.MethodsTranscriptome data and scRNA-seq data of ESCC samples were extracted from the GEO and TCGA databases. Tissue Specific Index (TSI) was defined to identify potential TIIC-RNAs from the TME. Twenty machine learning algorithms were further applied to evaluate the prognostic efficacy of TIIC signature score. Gene colocalization analysis was performed. Differences in CNV on chromosomes and SNP sites of prognostic model genes were calculated.ResultsThe most reliable model of TIIC signature score was developed based on three prognostic TIIC-RNAs. It showed a higher C-index than any other reported prognostic models. ESCC patients with high TIIC signature score showed poorer survival outcomes than low TIIC signature score. The activity of most immune cells decreased with the increase of TIIC score. TIIC signature score showed difference in the expression levels and methylation levels of DEGs. There was also significant different correlation with the degree of CNV amplification and CNV deletion of the immune checkpoint genes. Gene colocalization analysis showed two prognostic model genes (ATP6V0E1 and BIRC2). MR analysis found that rs148710154 and rs75146099 SNP sites of TIIC-RNA gene had a significant correlation between them gastro-oesophageal reflux and ESCC.ConclusionTIIC signature score was the first time developed which provided a novel strategy and guidance for the prognosis and immunotherapy of ESCC. It also gave the evidence in the important role of immune cells from the TME in the treatment of cancers.