Prognosis Of Esophageal Squamous Cell Carcinoma Research Articles

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.

Impact of APOBEC3s on the occurrence, development and prognosis of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a severe malignant tumor of the digestive system that poses a significant threat to human health. Despite its significance, the complex molecular mechanism regulating the occurrence and development of ESCC remain elusive. The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) members constitute a pivotal subfamily of the APOBEC family that possess cytidine deaminase activity. In recent years, APOBEC3s (A3s) have received increasing attention due to their pivotal roles in the occurrence, development, and prognosis of ESCC. This comprehensive review systematically summarizes the latest research progress on the mechanisms of action of A3s in ESCC and discusses their impact on the development and therapeutic considerations for ESCC, with a particular focus on their potential role in immunotherapy. These insights may be of great value in continued exploration of ESCC pathogenesis and provides a theoretical foundation for the development of clinical treatment strategies for ESCC.

GPR37-enhanced ubiquitination of ATP1A1 inhibits tumor progression and radiation resistance in esophageal squamous cell carcinoma

Radiotherapy resistance is one of the main reasons for the dismal clinical outcome of patients with esophageal squamous cell carcinoma (ESCC). Therefore, clarifying the targets and molecular mechanisms of radiotherapy resistance in ESCC is of great theoretical and clinical significance to enhance the efficacy of radiotherapy. In this study, GPR37 was identified as a key factor facilitating ESCC radiosensitization. We found that GPR37 is lowly expressed in ESCC, especially in radioresistant ESCC tumors. And its insufficiency is related to the malignant characteristics and unfavorable prognosis in ESCC. Further investigation revealed that GPR37 level is inversely regulated by promoter methylation but positively regulated by ZNF750. Functionally, GPR37 could not only overcome radioresistance of ESCC, but also inhibit proliferation, migration, and invasion. Mechanistically, GPR37 interacts with the ATP1A1 protein, effectively promoting its ubiquitination-induced degradation, thereby limiting the activation of the AKT/mTOR signaling pathway. Additionally, GPR37 can be transported to recipient cells via exosomes and inhibit the malignant behavior of recipient cells. Overall, these findings suggest that GPR37-ATP1A1 axis holds potential as a therapeutic target for the management of ESCC, especially for overcoming radiation resistance.

Expression and correlation of Surfeit 4 gene in esophageal squamous cell carcinoma

BackgroudIn the previous era of functional genomics, it was widely believed that the expression levels of housekeeping genes (HKGs) remained relatively constant and were unaffected by variations in tissue type, cell development stage, cell cycle state, as well as internal and external cellular environments. With the improvement of gene microarray technology and quantitative polymerase chain reaction (qPCR) technology for expression analysis of high-throughput differential genes, changes in the expression levels of HKGs have been found in certain human cancers. The present study aimed to experimentally validate the expression of Surfeit 4 gene (SURF4), a member of HKGs, in esophageal squamous cell carcinoma (ESCC).MethodsThe experimental techniques employed in this study encompassed real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), Western blot (WB), and immunohistochemistry (IHC) to assess the mRNA and protein expression of SURF4 in ESCC, and their clinicopathological significance was statistically analyzed.ResultsAll three tests showed significant differences between the three groups (Kruskal–Wallis test, P < 0.05). The results of the three methods indicated a significantly higher expression of SURF4 in the tumor group compared to both the adjacent paracancerous tissue group and the normal esophageal mucosal tissue group distant from the tumor. There was no significant difference between the latter two groups. Chi-square and Rank-sum test revealed the expression of SURF4 was significant statistical correlation with tumor cell differentiation, tumor progression and Ki-67 index, as well as the survival prognosis of patients (P < 0.05).ConclusionsThe expression of SURF4 was up-regulated in ESCC and was associated with differentiation, proliferation, progression, and clinical prognosis of ESCC. This portended epigenetically that SURF4 may play a role in tumor progression in ESCC and could potentially serve as a novel therapeutic target.

The roles of G protein-coupled receptor genes and the tumor microenvironment in esophageal squamous cell carcinoma

Abstract Objectives Esophageal squamous cell carcinoma (ESCA) is a challenging disease characterized by a high mortality rate. Understanding the prognostic relationship between G protein-coupled receptors (GPR) and ESCA is critical for improving patient outcomes, yet this connection remains to be fully explored. Methods In this study, we examined the roles of GPR genes and the tumor microenvironment (TME) in ESCA development and progression. Cox regression and Kaplan–Meier analysis demonstrated the predictive value of these genes. Our analysis of TME cell-cell communication revealed extensive interactions, particularly involving neutrophils. We also assessed the combined predictive value of GPR genes, TME score, and tumor mutation burden (TMB) for patient prognosis in ESCA, ultimately constructing a GPR-TME-TMB classifier for prognosis prediction. Results We identified significant differences in GPR gene expression between normal and tumor tissues, with four genes (GPER1, GPR82, FFAR2, and HCAR3) correlating with patient prognosis. Single-cell RNA sequencing analysis revealed 10 major cell types in the TME, with GPR gene expression highly enriched in neutrophils. Our findings indicate that the GPR-TME-TMB classifier is strongly associated with patient prognoses. Additionally, our results align with previous studies on the roles of GPR genes and the TME in ESCA. Conclusions Our results suggest that GPR-related genes play a role in ESCA progression and are strongly associated with TME in ESCA. We constructed a GPR-TME classifier for ESCA to provide new directions for the treatment and prognosis of ESCA patients.

Pathological features of the differentiation landscape in esophageal squamous cell cancer and their correlations with prognosis.

For esophageal squamous cell carcinoma (ESCC), universally accepted pathological criteria for classification by differentiation degree are lacking. Tumor budding, single-cell invasion, and nuclear grade, recognized as prognostic factors in other carcinomas, have rarely been investigated for their correlation with differentiation and prognosis in ESCC. This study aims to determine if pathological findings can predict differentiation degree and prognosis in ESCC. This study reviewed tumor slides from 326 patients who underwent surgery for ESCC between 2007 and 2012. Tumors were evaluated for subtypes, tumor nest size, tumor stroma, and nuclear grade (nuclear diameter and mitosis) across different differentiation groups. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, with group differences assessed using the stratified log-rank test and Cox proportional hazards model. The mean values of tumor budding invasion margins in well, moderately, and poorly differentiated groups were 25.3%, 30.7%, and 36.3%, respectively. Mean tumor budding/10HPFs were 8.0, 10.3, and 13.0, respectively. Well-differentiated tumors showed more keratinizing subtypes, smaller tumor budding invasion margins, more Grade 1 tumor budding (0-4 cells), absence of single-cell invasion, larger nuclear diameter (≥5 lymphocytes), higher mitotic counts, more submucosal invasion, and less lymphovascular invasion. Conversely, poorly differentiated tumors exhibited opposite characteristics. Multivariate analyses identified the nuclear diameter as independent prognostic factors for OS and DFS. Pathological features can stratify the differentiation landscape in ESCC patients. The nuclear diameter (4 lymphocytes) can help predict prognosis in ESCC than other pathological features. We first time report the mean values of tumor budding invasion margins and tumor budding/10HPF in well, moderately, and poorly differentiated groups for esophageal squamous cell carcinoma. The landscape of well differentiation was depicted with more keratinizing subtypes, smaller tumor budding invasion margins, more Grade 1 tumor budding (0-4 cells), absence of single-cell invasion, larger nuclear diameter (≥5 lymphocytes), higher mitotic counts, and less lymphovascular invasion. The nuclear diameter as independent prognostic factors for prognosis. The findings indicate that pathological features can stratify the differentiation landscape in ESCC patients and offer novel insight into definition of well or moderately differentiation.

Discovery and validation of Hsa-microRNA-3665 promoter methylation as a potential biomarker for the prognosis of esophageal squaous cell carcinoma.

Methylation of microRNA (miRNA) promoters associated with diseases is a common epigenetic mechanism in the development of various human cancers. However, its relationship with prognosis in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to explore the association between the methylation level of has-miR-3665 promoter and prognosis in ESCC. Human miRNA data were downloaded from miRbase, and we identified CpG islands of these human miRNAs by genomics browser analysis. MiRNA methylation levels were detected by methylation-specific high-resolution melting. Gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to explore the molecular mechanism of hsa-miR-3665. Cox regression analysis was used to investigate prognostic factors. The overall survival rate was predicted by a nomogram. We found that 88 human miRNAs had promoter methylatio, of which 15 miRNAs were found to be epigenetically regulated in ESCC cells compared with their normal counterparts, including hsa-miR-3665. Meanwhile, hsa-miR-3665 expression was significantly lower in ESCC tumour tissue than in adjacent tissue (P = 0.03). GO and KEGG analyses demonstrated that the target genes are involved in protein transport, transcription regulator activity, MAPK and RAS signaling pathway. High hsa-miR-3665 promoter methylation levels were associated with a poor prognosis (HR = 3.89, 95% CI 1.11 ~ 13.55). Moreover, a nomogram incorporating the hsa-miR-3665 methylation level and clinical factors presented a good performance for predicting survival in the training and validation tests, with C-indices of 0.748 and 0.751, respectively. High hsa-miR-3665 promoter methylation levels may be a potential biomarker for the progression of ESCC.

LncRNAs SOX2-OT and NEAT1 act as a potential biomarker for esophageal squamous cell carcinoma

Despite strides in diagnostic and therapeutic approaches for ESCC, patient survival rates remain relatively low. Recent studies highlight the pivotal role of long non-coding RNAs (lncRNAs) in regulating diverse cellular activities in humans. Dysregulated lncRNAs have emerged as potential diagnostic indicators across various cancers, including ESCC. However, further research is necessary to effectively leverage ESCC-associated lncRNAs in clinical settings. Understanding their clinical significance for ESCC diagnosis and their mechanisms can pave the way for more effective therapeutic strategies. Our qRT-PCR analysis revealed significant downregulation of SOX2-OT (~ 2.02-fold) and NEAT1 (~ 1.53-fold) in ESCC blood samples. These lncRNAs show potential as biomarkers for distinguishing ESCC patients from healthy individuals, with ROC curves and AUC values of 0.736 for SOX2-OT and 0.621 for NEAT1. Further analysis examined the correlation between SOX2-OT and NEAT1 expression and various clinicopathological factors, including age, gender, smoking, alcohol use, hot beverage intake, tumor grade, and TNM stages. In-silico studies highlighted their roles in miRNA sponging via mTOR and MAPK pathways, while co-expression network analysis identified associated genes. This research paves the way for future studies on ESCC prognosis using SOX2-OT and NEAT1 as predictive markers. By thoroughly investigating the functions of these lncRNAs, we aim to deepen our understanding of their potential as diagnostic markers and their role in facilitating effective therapeutic interventions for esophageal squamous cell carcinoma (ESCC) within clinical contexts.

Identification of key genes to predict response to chemoradiotherapy and prognosis in esophageal squamous cell carcinoma.

Chemoradiotherapy is a crucial treatment modality for esophageal squamous cell carcinoma (ESCC). This study aimed to identify chemoradiotherapy sensitivity-related genes and analyze their prognostic value and potential associations with the tumor microenvironment in ESCC. Utilizing the Gene Expression Omnibus database, we identified differentially expressed genes between ESCC patients who achieved complete and incomplete pathological responses following chemoradiotherapy. Prognostic genes were then screened, and key genes associated with chemoradiotherapy sensitivity were determined using random survival forest analysis. We examined the relationships between key genes, infiltrating immune cells, and immunoregulatory genes. Additionally, drug sensitivity and enrichment analyses were conducted to assess the impact of key genes on chemotherapy responses and signaling pathways. A prognostic nomogram for ESCC was developed incorporating key genes, and its effectiveness was evaluated. Genome-wide association study data were employed to investigate chromosomal pathogenic regions associated with key genes. Three key genes including ATF2, SLC27A5, and ALOXE3 were identified. These genes can predict the sensitivity of ESCC patients to neoadjuvant chemoradiotherapy and hold significant clinical relevance in prognostication. These genes were also found to be significantly correlated with certain immune cells and immunoregulatory genes within the tumor microenvironment and were involved in critical tumor-related signaling pathways, including the epithelial-mesenchymal transition and P53 pathways. A nomogram was established to predict the prognosis of ESCC by integrating key genes with clinical stages, demonstrating favorable predictability and reliability. This study identified three key genes that predict chemoradiotherapy sensitivity and prognosis and are involved in multiple tumor-related biological processes in ESCC. These findings provide predictive biomarkers for chemoradiotherapy response and support the development of individualized treatment strategies for ESCC patients.

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

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

Impact of Mitophagy-Related Genes on the Diagnosis and Development of Esophageal Squamous Cell Carcinoma via Single-Cell RNA-seq Analysis and Machine Learning Algorithms.

As a treatment for esophageal squamous cell carcinoma (ESCC), which is common and fatal, mitophagy is a conserved cellular mechanism that selectively removes damaged mitochondria and is crucial for cellular homeostasis. While tumor development and resistance to anticancer therapies are related to ESCC, their role in ESCC remains unclear. Here, we investigated the relationship between mitophagy-related genes (MRGs) and ESCC to provide novel insights into the role of mitophagy in ESCC prognosis and diagnosis prediction. First, we identified MRGs from the GeneCards database and examined them at both the single-cell and transcriptome levels. Key genes were selected and a prognostic model was constructed using least absolute shrinkage and selection operator analysis. External validation was performed using the GSE53624 dataset and Kaplan-Meier survival analysis was performed to identify PYCARD as a gene significantly associated with survival in ESCC. We then examined the effect of PYCARD on ESCC cell proliferation and migration and identified 169 MRGs at the single-cell and transcriptome levels, as well as the high-risk groups associated with cancer-related pathways. Thirteen key genes were selected for model construction via multiple machine learning algorithms. PYCARD, which is upregulated in patients with ESCC, was negatively correlated with prognosis and its knockdown inhibited ESCC cell proliferation and migration. Our ESCC prediction model based on mitophagy-related genes demonstrated promising results and provides more options for the management and clinical treatment of ESCC patients. Moreover, targeting or regulating PYCARD levels might offer new therapeutic strategies for ESCC patients in clinical settings.

Plasma Cytokines Pattern as a Prognostic Marker for Esophageal Squamous Cell Carcinoma via Unsupervised Clustering Analyses

Introduction: Cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL6), interferon-gamma (IFN-γ), interleukin 17-alpha (IL17-α), and interleukin 33 (IL33) play critical roles in immune responses and may impact cancer prognosis in future. However, few studies have simultaneously explored the prognostic impact of these cytokines for cancer. In this study, we aim to apply the unsupervised clustering analysis to approach the correlation between the expression of these cytokines and the subsequent prognosis of patients with esophageal squamous cell carcinoma (ESCC). Methods: A robust clustering algorithm was used, the Gaussian mixture method (GMM), through the mclust R package to group patients based on the expression of their cytokines in plasma or tumors. The 324 NTU patients were grouped into 4 clusters, and the 179 GSE53625 patients were grouped into 3 clusters based on expression in plasma and tumors, respectively. Five- and 3-year overall survival (OS) and progression-free survival (PFS) curves of each cluster were compared. Univariate and multivariate Cox regression analyses were also performed. Results: We successfully distinguished the multimodal distribution of cytokines through GMM clustering and discovered the relationship between cytokines and clinical outcomes. We observed that NTU-G3 and NTU-G4 subgroups showed most variation in 5-, 3-year OS and 5-, 3-year PFS with NTU-G3 being associated with poorer prognosis compared to NTU-G4 (p = 0.016, 0.0052, 0.0575, and 0.0168, respectively). NTU-G3 was characterized with higher TNF-α (median = 3.855, N = 78) and lower IL33 (median = 0.000, N = 78), while NTU-G4 showed lower TNF-α (median = 1.76, N = 51) and higher IL33 (median = 1.070, N = 51). The difference was statistically significant for TNF-α and IL33, with p = 0.0002 and p < 0.0001, respectively. A multivariate Cox-regression analysis revealed that GMM clustering and T/N stage were independent factors for prognosis, suggesting that the prognosis might be dependent on these cytokines. Conclusions: Our data suggest that expression patterns of IL33 and TNF-α in plasma might serve as a convenient marker to predict the prognosis of ESCC in the future.

Identifying Survival Subtypes of Esophageal Squamous Cell Carcinoma Patients: An Application of Deep Learning in Gene Expression Data Analysis

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most lethal types of cancer. Late diagnosis significantly decreases patient survival rates. Objectives: The study aimed to identify survival groups for patients with ESCC and find predictive biomarkers of time-to-death from ESCC using state-of-the-art deep learning (DL) and machine learning algorithms. Methods: Expression profiles of 60 ESCC patients, along with their demographic and clinical variables, were downloaded from the GEO dataset. A DL autoencoder model was employed to extract lncRNA features. The univariate Cox proportional hazard (Cox-PH) model was used to select significant extracted features related to patient survival. Hierarchical clustering (HC) identified risk groups, followed by a decision trees algorithm which was used to identify lncRNA profiles. We used Python.3.7 and R.4.0.1 software. Results: Inputs of the autoencoder were 8,900 long noncoding RNAs (lncRNAs), of which 1000 features were extracted. Out of the features, 42 lncRNAs were significantly related to time-to-death using the Cox-PH model and used as input for clustering of patients into high and low-risk groups (P-value of log-rank test = 0.022). These groups were then labeled for supervised HC. The C5.0 algorithm achieved an overall accuracy of 0.929 on the test set and identified four hub lncRNAs associated with time-to-death. Conclusions: Novel discovered lncRNAs lnc-FAM84A-1, LINC01866, lnc-KCNE4-2 and lnc-NUDT12-4 implicated in the pathogenesis of death from ESCC. Our findings represent a significant advancement in understanding the role of lncRNAs on ESCC prognosis. Further research is necessary to confirm the potential and clinical application of these lncRNAs.

Extracellular glypican-1 affects tumor progression and prognosis in esophageal cancer.

Cells are covered with a glycan surface layer that is referred to as the glycocalyx (GCX). It has been reported that the formation of the GCX is promoted on cancer cells and is associated with tumor growth and metastasis. Heparan sulfate proteoglycan glypican-1 (GPC1) is a core protein of the GCX that is overexpressed in esophageal squamous cell carcinoma (ESCC) and is involved in the development and progression of cancer cells. The purpose of the present study is to analyze the utility of GPC1 as a new biomarker ralated to glycocalyx that reflects therapeutic effect and prognosis of ESCC. We measured the concentration of GPC1 protein in preoperative plasma from advanced esophageal cancer patients and examined its relationships with clinicopathological factors and therapeutic efficacy, and the effects of extracellular GPC1 were investigated. The following clinical factors were significantly correlated with the preoperative high GPC1 concentration: male, tumor size ≥30 mm, venous invasion, pT factor ≥2, pStage ≥3, residual tumor, and distant metastatic recurrence. Both overall and recurrence-free survival were significantly worse in the high GPC1 group. Extracellular GPC1 protein concentration reflected intracellular GPC1 expression. Furthermore, we examined the effects of extracellular recombinant human (rh)GPC1 on ESCC cells, and found that extracellular rhGPC1 affects cell motility, including migration and invasion. These results demonstrated the utility of extracellular GPC1 as a biomarker, which can be assayed from a less invasive blood sample-based liquid biopsy. Extracellular GPC1 protein plays a role in both tumor cell motility and cancer progression. Thus, plasma GPC1 is a useful biomarker for esophageal cancer progression and may be a potential candidate of therapeutic target.

401. CLINICAL SIGNIFICANCE OF SIGNAL REGULATORY PROTEIN ALPHA AND CLUSTER OF DIFFERENTIATION 47 EXPRESSION IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background This study focuses on assessing the expression of Signal Regulatory Protein Alpha (SIRPα) and Cluster of Differentiation 47 (CD47) in Esophageal Squamous Cell Carcinoma (ESCC) and their impact on prognosis. Given the prominence of the CD47-SIRPα axis in cancer for inhibiting macrophage-mediated phagocytosis, this research aims to explore their role and significance in the development and treatment of ESCC. Methods In this study, 100 ESCC patients who underwent esophagectomy were included. Resected specimens were stained immunohistochemical staining for SIRPα and CD47. SIRPα expression was classified as high or low with cut-off value of 3%. CD47 expression was evaluated by Combined Positive Score (CPS) and Tumor Proportion Score (TPS) methods with setting a 10% threshold for high and low expression. The five-year survival rates were compared across groups over a median observation period of 61 months. This study reveals the correlation between these biomarkers and postoperative prognosis. Results Total 79 males and 21 females were included in this study and mean age was 68.7-year-old. The high SIRPα expression group (48 patients) revealed significantly worse 5-year overall survival rate than the low expression group (52 patients) (56.4 vs 82.8%, P=0.0098). For CD47, both evaluated by using CPS and TPS, the high expression group also showed significantly worse 5-year overall survival rate than its low group (48.8 vs 89.5%, P&amp;lt;0.0001, and 48.4 vs 87.5%, P&amp;lt;0.0001 respectively). Relapse free survival also showed significantly worse survival rate in high expression group of SIRPα and CD47. Conclusion The expression levels of SIRPα and CD47 serve as important biomarkers for predicting the prognosis of ESCC. They may influence prognosis by inhibiting macrophage-mediated tumor cell phagocytosis and modulating anti-tumor immune responses, offering new targets for ESCC treatment.

240. CACHEXIA INDEX AS A POTENTIAL BIOMARKER FOR SENSITIVITY OF NEOADJUVANT THERAPY AND PROGNOSIS IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background Cancer cachexia has a negative impact on the clinical outcome of patients with esophageal squamous cell carcinoma (ESCC). The cachexia index (CXI) is a potential biomarker for cancer cachexia, whereas its implications for ESCC prognosis and treatment outcomes have not been investigated. Methods In our study, 454 ESCC patients who had neoadjuvant therapy followed by surgery were included. Based on the exclusion criteria, a total of 224 patients were finally enrolled in this study. The CXI was determined as the serum albumin/neutrophil-lymphocyte ratio × the skeletal muscle index (based on CT image), which was classified as L3-CXI or pectoralis muscles-CXI depending upon the type of muscle involved. The patients were divided into high- and low-CXI groups using sex-specific medians as cutoff values for CXI. Results Tumor regression grade = 0,1 (sensitive to treatment) to neoadjuvant therapy was obtained in 61.6% and 46.4% of patients in the high-pretreatment L3-CXI and low-pretreatment L3-CXI groups, respectively (P = 0.023). ESCC patients with △L3-CXI &amp;lt;0 (L3-CXI decreased during treatment) had significantly shorter overall survival (P = 0.006) and disease-free survival (P = 0.002) than those with △L3-CXI ≥0. Multivariable analysis showed that △L3-CXI &amp;lt;0 was an independent negative prognostic factor for overall survival and disease-free survival. Conclusions In patients with ESCC, pretreatment CXI is a biomarker for treatment response, and △CXI can predict postoperative complications and survival outcomes. Patients could be clearly stratified by pretreatment CXI and △CXI categories, which provides a new nutritional assessment tool for clinical decision-making for patients with ESCC.

569. PROGNOSTIC VALUE OF T CELL PHENOTYPES AND PD-L1 EXPRESSION IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Backgrounds The tumor microenvironment (TME) is a complex niche for tumor cells and immune cells to survive. Tumor-infiltrating lymphocytes (CD8+ T cells, FoxP3+ Tregs…etc), one of the main components of TME, are key factors in the host-tumor immune response, and the exact immune response in esophageal squamous cell carcinoma (ESCC) is still unclear. The purpose of this study was to investigate the expression of PD-L1 and TILs phenotypes in ESCC, their interactions and clinical significance. Methods Surgical specimens from 126 ESCC patients who underwent curative surgery between January 2001 and April 2017. We performed immunophenotyping of CD4, CD8, CD25, FOXP3 and PD-L1 within the tumor using immunohistochemistry and multiple immunofluorescence immunolabeling. PD-L1 was detected to expressed on tumor cells (PD-L1 TC) and tumor-infiltrating immune cells (PD-L1 TIIC), and PD-L1 TC affect biologic behavior. The calculation of overall survival (OS) and recurrence-free survival (RFS) were made using Kaplan-Meier analysis, and Cox regression model was used to analyze the correlation between survival and prognosis. Results CD8, FoxP3 and PD-L1 expression were positive in 40 (31.7%), 55 (43.7%) and 35 (27.8%) ESCC patient, respectively. CD8 and FoxP3 positive were associated with prolonged OS (p=0.0028, p=0.0324, respectively) and RFS (p=0.0019, p=0.0628, respectively). The overall survival rate in the PD-L1 positive group was statistically lower than that in the negative group (p=0.0402). Furthermore, the combination of CD8/PD-L1 and CD8/Foxp3 was able to more clearly classify and predict prognostic groups of ESCC. Considering the Treg phenotype, the presence of triple positive cell infiltration with Foxp3, CD4, and CD25 was strongly associated with poor prognosis of ESCC (p=0.0349). Cox proportional hazard model suggested that tumor depth, CD8+ infiltration and PD-L1 expression were significantly correlated with overall survival. CD8+ infiltration and PD-L1 expression were revealed to be independent prognostic factors. Conclusion CD8 and PD-L1 expression are independent prognostic and predictive factors for ESCC. And it is necessary to elucidate the immune mechanism comprehensively and thoroughly in the insight of multidimensional, multi-molecular and to provide therapeutic strategies for immunotherapy of ESCC.

T cell-related circRNA pairs to predict prognosis of patients with esophageal squamous cell carcinoma

The prognosis for esophageal squamous cell carcinoma (ESCC), a prevalent and aggressive form of cancer, remains poor despite advancements in treatment options. Addressing the gap in comprehensive prognostic information derived from circRNA expression profiles for ESCC, our study aimed to establish a linkage between circRNA expressions and ESCC prognosis. To achieve this, we first developed an optimized prognostic model named T cell-related risk score (TRRS), which integrates T cell-associated features with machine learning algorithms. In parallel, we re-analyzed existing RNA-seq datasets to redefine the expression profiles of circRNAs and mRNAs. Utilizing the TRRS as a foundational “bridge,” we identified circRNAs correlated with TRRS, leading to the development of a novel circRNA pair-based prognostic model, the TCRS, which is independent of specific expression levels. Further investigations uncovered two circRNAs, circNLK(5,6,7).1 and circRC3H1(2).1, with potential functional significance. These findings underscore the utility of these risk scores as tools for predicting overall survival and identifying potential therapeutic targets for ESCC patients.

Screening of genes related to programmed cell death in esophageal squamous cell carcinoma and construction of prognostic model based on transcriptome analysis

ABSTRACT Objectives To screen programmed cell death (PCD)-related genes in esophageal squamous cell carcinoma (ESCC) based on transcriptomic data and to explore its clinical value. Methods Differentially expressed PCD genes (DEPCDGs) were screened from ESCC transcriptome and clinical data in TCGA database. Univariate COX and LASSO COX were performed on prognostically DEPCDGs in ESCC to develop prognostic model. Differences in immune cell infiltration in different RiskScore groups were determined by ssGSEA and CIBERSORT. The role of RiskScore in immunotherapy response was explored using Tumor Immune Dysfunction and Exclusion (TIDE) and IMvigor210 cohorts. Results Fourteen DEPCDGs associated with prognosis were tapped in ESCC. These DEPCDGs form a RiskScore with good predictive performance for prognosis. RiskScore demonstrated excellent prediction accuracy in three data sets. The abundance of M2 macrophages and Tregs was higher in the high RiskScore group, and the abundance of M1 macrophages was higher in the low RiskScore group. The RiskScore also showed good immunotherapy sensitivity. RT-qPCR analysis showed that AUP1, BCAP31, DYRK2, TAF9 and UBQLN2 were higher expression in KYSE-150 cells. Knockdown BCAP31 inhibited migration and invasion. Conclusion A prognostic risk model can predict prognosis of ESCC and may be a useful biomarker for risk stratification and immunotherapy assessment.

Comparative evaluation of imaging methods for prognosis assessment in esophageal squamous cell carcinoma: focus on diffusion-weighted magnetic resonance imaging, computed tomography and esophagography.

To identify the most sensitive imaging examination method to evaluate the prognosis of esophageal squamous cell carcinoma (ESCC). Thirty patients with esophageal squamous cell carcinoma (ESCC) participated in the study and underwent chemoradiotherapy (CRT). They were divided into two groups based on their survival status: the survival group and non-survival group. The diagnostic tests were utilized to determine the most effective imaging examination method for assessing the prognosis. 1. There were no significant differences in tumor length shown on esophagography or computed tomography (CT) or the maximal esophageal wall thickness shown on CT at the specified time points between the two groups. 2. The tumor length on diffusion-weighted imaging (DWI) in the survival group was significantly lower than in the non-survival group at the end of the sixth week of treatment (P=0.001). The area under the ROC curve was 0.840 (P=0.002), and the diagnostic efficiency was moderately accurate. 3. The apparent diffusion coefficient (ADC) values of the survival group were significantly higher than those in the non-survival group at the end of the fourth week and sixth week of treatment (both P<0.001). Areas under the curve were 0.866 and 0.970, with P values of 0.001 and <0.001 and good diagnostic accuracy. Cox regression analyses indicated the ADC at the end of the sixth week of treatment was an independent risk factor. Compared with esophagography and CT, DW-MRI has certain advantages in predicting the prognosis of ESCC.