Prognosis Of Esophageal Cancer Patients Research Articles

Rhein suppresses esophageal cancer development by regulating cell cycle through DNMT3B gene.

The mechanism by which DNMT3B facilitates esophageal cancer (ESCA) progression is currently unknown, despite its association with adverse prognoses in several cancer types. To investigate the potential therapeutic effects of the Chinese herbal medicine rhubarb on esophageal cancer (ESCA), we adopted an integrated bioinformatics approach. Gene Set Enrichment Analysis (GSEA) was first utilized to screen active anti-ESCA components in rhubarb. We then employed Weighted Gene Co-expression Network Analysis (WGCNA) to identify key molecular modules and targets related to the active components and ESCA pathogenesis. This system-level strategy integrating multi-omics data provides a powerful means to unravel the molecular mechanisms underlying the anticancer activities of natural products, like rhubarb. To investigate module gene functional enrichment, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. In addition, we evaluated the predictive impact of DNMT3B expression on ESCA patients utilizing the Kaplan-Meier method. Finally, we conducted experiments on cell proliferation and the cell cycle to explore the biological roles of DNMT3B. In this study, we identified Rhein as the main active ingredient of rhubarb that exhibited significant anti-ESCA activity. Rhein markedly suppressed ESCA cell proliferation. Utilizing Weighted Gene Co-expression Network Analysis (WGCNA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we determined that the blue module was associated with Rhein target genes and the cell cycle. Additionally, DNMT3B was identified as a Rhein target gene. Analysis of The Cancer Genome Atlas (TCGA) database revealed that higher DNMT3B levels were associated with poor prognosis in ESCA patients. Furthermore, Rhein partially reversed the overexpression of DNMT3B to inhibit ESCA cell proliferation. In vitro studies demonstrated that Rhein and DNMT3B inhibition disrupted the S phase of the cell cycle and affected the production of cell cycle-related proteins. In this study, we found that Rhein exerts its anti-proliferative effects in ESCA cells by targeting DNMT3B and regulating the cell cycle.

Association between plasma circulating tumor DNA and the prognosis of esophageal cancer patients: a meta-analysis.

The application of liquid biopsy analysis utilizing circulating tumor DNA (ctDNA) has gained prominence as a biomarker in specific cancer types. Nevertheless, the correlation between ctDNA and the prognostic outcomes of patients with esophageal cancer (EC) remains a subject of controversy. This meta-analysis aims to assess the correlation between ctDNA and the prognosis of EC patients. We systematically explored Embase, PubMed, and the Cochrane Database to identify studies reporting on the prognostic value of ctDNA in EC patients before November 2023. The primary outcome involved the determine of associations between ctDNA with overall survival (OS), disease-free survival (DFS)/recurrence-free survival (RFS), as well asprogression-free survival (PFS) among EC patients. Secondary outcomes encompassed a detailed subgroup analysis in the setting of EC, including parameters such as detection time, histological subtypes, treatment modalities, regions, anatomic locations, and detection methods. Publication bias was assessed utilizing Begg's test, Egger's test, and funnel plots. A sensitivity analysis was conducted by systematically excluding individual studies to evaluate the stability of the results. A total of 1203 studies were initially screened, from which 13 studies underwent further analysis, encompassing 604 patients diagnosed with EC. The comprehensive pooled analysis indicated a significant association between the detection of ctDNA and poor OS (HR: 3.65; 95% CI: 1.97-6.75, P<0.001), DFS/RFS (HR: 6.08; 95% CI: 1.21-30.50, P<0.001), and PFS (HR: 2.84; 95% CI: 1.94-4.16, P<0.001). Subgroup analysis showed that ctDNA remained a consistent negative predictor of OS when stratified by different detection time, histological subtypes, regions, anatomic locations, and detection methods. Furthermore, subgroup analysis stratified by regions and study types demonstrated an association between ctDNA detection and poor PFS in EC patients. Our results indicate plasma ctDNA may serve as robust prognostic markers for OS, DFS/RFS, and PFS among EC patients. This finding suggests that plasma ctDNA could offer a highly effective approach for risk stratification and personalized medicine.

METTL3-mediated m6A modification of EPPK1 to promote the development of esophageal cancer through regulating the PI3K/AKT pathway.

Methyltransferase like 3 (METTL3) has been proved to be involved in the progression of various cancers. In this study, we explored the role of METTL3 and its underlying mechanism in esophageal cancer progression. The mRNA and protein levels of METTL3 and epiplakin1 (EPPK1) were determined using qRT-PCR and western blot. The proliferative ability was evaluated through 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT), colony formation, and EdU assays. Transwell invasion assay and wound-healing assay were employed for detecting cell invasion and migration, respectively. Cell stemness was evaluated by sphere-formation assay. Xenograft tumor experiments and immunohistochemistry (IHC) were performed to explore the effects of METTL3 knockdown on tumor growth in vivo. The N6-methyladenosine (m6A) modification of EPPK1 was analyzed using MeRIP. RNA-protein immunoprecipitation (RIP) and dual-luciferase reporter assays were used to verify the relationship between EPPK1 and METTL3. METTL3 was upregulated in esophageal cancer tissues and cells, which was related to the poor prognosis of esophageal cancer patients. Knockdown of METTL3 overtly decreased the proliferative, invasive, migrated abilities, and cell stemness of esophageal cancer cells in vitro. Moreover, depletion of METTL3 also observably suppressed the growth of tumor in vivo. EPPK1 was a direct target of METTL3, and METTL3 could mediate the m6A modification of EPPK1. EPPK1 was downregulated in esophageal cancer tissues and cells, and EPPK1 depletion markedly repressed cell proliferation, invasion, migration, and stemness of esophageal cancer cells. The inhibition effects of METTL3 deficiency on these malignant behaviors were harbored by EPPK1 upregulation in esophageal cancer cells. In addition, METTL3 deficiency reduced EPPK1 expression to inactivate the PI3K/AKT pathway. Our results revealed that METTL3 deficiency regulated the m6A modification of EPPK1 to inhibit the PI3K/AKT pathway, thereby restraining the progression of esophageal cancer.

FABP6 serves as a new therapeutic target in esophageal tumor.

Esophageal cancer is one of the most common malignant tumors with high incidence and mortality rates. Despite the continuous development of treatment options, the prognosis for esophageal cancer patients remains poor. Therefore, there is an urgent need for new diagnostic and therapeutic targets in clinical practice to improve the survival of patients with esophageal cancer. In this study, we conducted a comprehensive scRNA-seq analysis of the tumor microenvironment in primary esophageal tumors to elucidate cell composition and heterogeneity. Using Seurat, we identified eight clusters, encompassing non-immune cells (fibroblasts, myofibroblasts, endothelial cells, and epithelial cells) and immunocytes (myeloid-derived cells, T cells, B cells, and plasma cells). Compared to normal tissues, tumors exhibited an increased proportion of epithelial cells and alterations in immune cell infiltration. Analysis of epithelial cells revealed a cluster (cluster 0) with a high differentiation score and early distribution, suggesting its importance as a precursor cell. Cluster 0 was characterized by high expression of FABP6, indicating a potential role in fatty acid metabolism and tumor growth. T cell analysis revealed shifts in the balance between Treg and CD8+ effector T cells in tumor tissues. Cellular communication analysis identified increased interactions between FABP6+ tumor cells and T cells, with the involvement of the MIF-related pathway and the CD74-CD44 interaction. This study provides insights into the cellular landscape and immune interactions within esophageal tumors, contributing to a better understanding of tumor heterogeneity and potential therapeutic targets.

Preoperative and Postoperative C-Reactive Protein to Albumin Ratio (CAR) as a Prognostic Marker for Survival of Esophageal Squamous Cell Carcinoma Patients After Surgery.

Recent studies have reported that the C-reactive protein (CRP) to albumin ratio (CAR) may be a useful prognostic biomarker in various types of cancer patients. However, the mechanism underlying this observation is unclear. The present study aimed to clarify why the CAR can predict post-esophagectomy prognosis, the relationship between pre- and postoperative CAR, and whether postoperative CAR can predict the prognosis of esophageal cancer patients. We investigated 158 esophagectomy patients with esophageal squamous cell carcinoma. Hematological examinations were performed on postoperative days (POD) 1, 3, 5, 7, 10, and 14. Preoperative CAR was a significant independent prognostic factor of overall survival (OS) [hazard ratio (HR)=2.247; p=0.0005], and there was a strong correlation between preoperative CAR and tumor depth. The preoperative high-CAR (pre-high-CAR) group had significantly higher CAR on all postoperative days (POD). We then divided the patients as follows: those with at least two low-CAR days on POD 5, 7, and 10 were assigned to the modified post-low-CAR (mPost-low-CAR) group, and others were assigned to the modified post-high-CAR (mPost-high-CAR) group. The 5-year OS rate was significantly higher in the mPost-low-CAR group than in the mPost-high-CAR group, which predicted a more accurate prognosis (p<0.0001, HR=2.769). Preoperative CAR was associated with tumor depth and diameter, and patients in the pre-high-CAR group continued to have significantly higher CAR postoperatively. These factors were presumed to reflect disease prognosis. Furthermore, grouping by CAR on POD 5, 7, and 10 reflected patient prognosis more accurately than preoperative CAR.

MicroRNA-223 Suppresses the Progression of Esophageal Cancer by Negatively Regulating SMAD Family Member 4

The purpose of this study was to elucidate the biological role of MicroRNA-223 (miRNA-223) in mediating the malignant progression of esophageal cancer and the underlying mechanism. MiRNA-223 levels were measured using qRT-PCR in 50 paired esophageal cancer tissues and adjacent paracancerous tissues. The correlation between miRNA-223 level and pathological indicators in esophageal cancer patients was analyzed. In vitro experiments assessed the impact of miRNA-223 on the proliferative, migratory, and invasive abilities of esophageal cancer cells. Additionally, rescue experiments were conducted to investigate the involvement of miRNA-223 and its downstream target, SMAD4, in the progression of esophageal cancer. Esophageal cancer tissues showed decreased levels of miRNA-223 compared to adjacent tissues. Patients with low miRNA-223 exhibited higher rates of lymphatic and distant metastasis, as well as poorer overall survival than those with high miRNA-223 levels. Increasing miRNA-223 in TE-1 and EC-109 cells reduced their proliferative, migratory, and invasive capabilities. Esophageal cancer tissues and cell lines displayed elevated SMAD4 levels, which were negatively regulated by miRNA-223. Restoring SMAD4 expression partially reversed the inhibitory effects of miRNA-223 overexpression in esophageal cancer cells. MiRNA-223 is closely correlated to lymphatic metastasis, distant metastasis and poor prognosis of esophageal cancer patients. MiRNA-223 suppresses proliferative, migratory and invasive abilities of esophageal cancer cells via negatively regulating SMAD4.

Nomogram for predicting survival after lymphatic metastasis in esophageal cancer: A SEER analysis.

Lymphatic metastasis (LM) is a significant mechanism for the spread of esophageal cancer (EC) and predicts the poor prognosis of EC patients. This research aimed to assess the survival of patients with LM from EC by developing a nomogram. In this retrospective study, EC patients with LM from 2004 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were divided by year of diagnosis into a training cohort and a validation cohort. Univariate and multivariate Cox regression analyses were employed to determine the prognostic factors of LM, and a nomogram was constructed. The discrimination and calibration of the nomogram were compared by the C-index, area under the curve value, and calibration plots. The survival time difference was compared using Kaplan-Meier curves. A total of 11,695 patients with EC were included in this analysis. LM occurred in 56.5% (n = 6614) of EC patients. In the post-propensity score matching (PSM) cohort, patients with LM had significantly lower median overall survival (OS) than those without LM. Multivariate Cox regression was used to identify the eleven independent prognostic factors. The C-index was 0.709 in both the training and test sets, revealing the good predictive performance of the nomogram. Based on the results of calibration plots and the receiver operating characteristic (ROC) curve, we demonstrate the great performance of the prognostic model. The survival time of EC patients with LM was remarkably lower than that of EC patients without LM. The nomogram model established in this study can precisely predict the survival of EC patients with LM.

Characterization of pyroptosis-related genes in esophageal cancer and construction of a prognostic model.

Esophageal cancer (EC) is a highly malignant digestive system tumor that often lacks evident early symptoms and has a poor prognosis. Pyroptosis, a form of programmed cell death, has been shown to be associated with the occurrence and progression of many malignancies. However, its role in esophageal cancer remains unclear. This work aimed to evaluate the prognostic value of pyroptosis-related genes (PRGs) in EC using data from The Cancer Genome Atlas (TCGA) cohort. The RNA-seq data from 171 esophageal samples in the TCGA database were employed. Differential expression genes (DEGs) between tumor and non-tumor samples were compared. Protein-protein interaction (PPI) networks were constructed using the STRING database, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) analyses were performed using the "clusterProfiler" package in R. Furthermore, based on the DEGs, all esophageal cancer cases were classified into three subtypes. A risk model for gene features was established using the LASSO regression method, and EC patients in the TCGA cohort were divided into high-risk and low-risk groups. A total of 614 PRGs were identified. Among them, 32 DEGs (31 upregulated and 1 downregulated) were found between normal esophageal tissue and EC tissue. PPI analysis identified key genes including IL-1β, CASP1, AIM2, HMGB1, GSDMD, PYCARD, IL-18, BAK1, and TP53. On the other hand, the low-risk group exhibited a significantly higher survival rate than the high-risk group (p < 0.001). Combined with the clinical characteristics of the TCGA cohort, it was found that the risk score was an independent prognostic factor for overall survival (OS) prediction in EC patients. KEGG and GO analyses revealed the enrichment of genes associated with cell proliferation in the high-risk group. PRGs play a crucial role in the occurrence and development of EC and can be used to predict the prognosis of EC patients.

Prognostic value of pretreatment Controlling Nutritional Status score in esophageal cancer: a meta-analysis.

Background and purpose: The association between the pretreatment Controlling Nutritional Status (CONUT) score and the prognosis of esophageal cancer patients remains unclear. The aim of this meta-analysis was to further elucidate the prognostic role of the pretreatment CONUT score in esophageal cancer based on current evidence. Methods: The PubMed, Embase, Web of Science and CNKI databases were searched up to 27 September 2022. The primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS)/cancer-specific survival (CSS), and the hazard ratio (HR) and 95% confidence interval (CI) were pooled for analysis. Results: A total of 11 retrospective studies involving 3,783 participants were included. The pooled results demonstrated that a higher pretreatment CONUT score was significantly related to poor OS (HR = 1.82, 95% CI: 1.31-2.54, p < 0.001), and subgroup analysis stratified by pathological type showed similar results. In addition, the pretreatment CONUT score was associated with poor PFS (HR = 1.19, 95% CI: 1.10-1.28, p < 0.001) and CSS (HR = 2.67, 95% CI: 1.77-4.02, p < 0.001). Conclusion: The pretreatment CONUT score was predictive of worse prognosis in esophageal cancer, and patients with a higher CONUT score showed worse survival.

The crucial role of high C-reactive protein interval and Glasgow prognostic score for predicting prognosis in esophageal cancer patients undergoing chemoradiotherapy

The crucial role of high C-reactive protein interval and Glasgow prognostic score for predicting prognosis in esophageal cancer patients undergoing chemoradiotherapy

Role of exosomal noncoding RNA in esophageal carcinoma.

Esophageal cancer is a common malignant tumor with a high degree of malignancy. Understanding its pathogenesis and identifying early diagnostic biomarkers can significantly improve the prognosis of esophageal cancer patients. Exosomes are small double-membrane vesicles found in various body fluids containing various components (DNA, RNA, and proteins) that mediate intercellular signal communication. Non-coding RNAs are a class of gene transcription products that encode polypeptide functions and are widely detected in exosomes. There is growing evidence that exosomal non-coding RNAs are involved in cancer growth, metastasis and angiogenesis, and can also be used as diagnostic and prognostic markers. This article reviews the recent progress in exosomal non-coding RNAs in esophageal cancer, including research progress, diagnostic value, proliferation, migration, invasion, and drug resistance, provide new ideas for the precise treatment of esophageal cancer.

Relationship Between CD8+ T Cells and Prognosis of Esophageal Cancer Patients: A Systematic Review and Meta-analysis.

Tumor infiltrating lymphocytes (TILs), especially CD8+ T cells, play an important role in the process of anti-tumor immune response and are significantly correlated with the prognosis of esophageal cancer (EC), but there are also inconsistent conclusions. This study aimed to comprehensively evaluate the relationship between invasive CD8+ T cells and the prognosis in patients with EC through meta-analysis, and to provide a basis for prognosis and immunotherapy for EC. Articles related to CD8+ T cells and EC prognosis in PubMed, Cochrane Library, Embase, and CNKI were searched. Cancer specific survival (CSS), overall survival (OS) and disease-free survival (DFS) served as endpoint events. Besides, Stata15.0 was adopted for meta-analysis, and hazard ratio (HR) and 95% confidence interval (95%CI) for calculation of combined effect sizes. Total 547 articles were retrieved and 27 articles were finally enrolled, including 3988 cases of EC patients. Meta-analysis showed that high CD8 expression levels in tumor tissues, especially those in cancer nests, were associated with longer OS (HR = 0.74, 95% CI 0.67-0.81) and DFS (HR = 0.90, 95% CI 0.85-0.95) in EC patients (P < 0.05). CD8+ T cells play an important role in the prognosis of EC patients and are indispensable components for the immune score of EC.

MicroRNA-532 Promotes Proliferation, Metastasis and Autophagy in Esophageal Cancer via Targeting Naked Cuticle 1

The aim of this study was to elucidate the role of microRNA-532 in influencing the progression of esophageal cancer and cell autophagy through negatively regulating Naked cuticle 1 (NKD1) level. Relative levels of microRNA-532 and NKD1 in esophageal cancer tissues and corresponding paracancerous ones were detected. The relationship between microRNA-532 level and overall survival in esophageal cancer patients was statistically analyzed. Subsequently, regulatory effects of microRNA-532 and NKD1 on viability, metastasis and autophagy in TE-1 and EC-109 cells were examined. The interaction between microRNA-532 and NKD1 was finally explored. MicroRNA-532 was upregulated in esophageal cancer tissues and its high level indicated poor prognosis in esophageal cancer patients. Serving as the downstream gene binding microRNA-532, NKD1 level was negatively regulated by microRNA-532. Knockdown of microRNA-532 weakened viability and metastasis, as well as downregulated autophagy-associated genes (Atg5, LC-3I and LC-3II) in TE-1 and EC-109 cells. Knockdown of NKD1 achieved the opposite results. MicroRNA-532 promotes proliferation, metastasis and autophagy in esophageal cancer by downregulating NKD1. It is believed that microRNA-532 may be a promising therapeutic target for esophageal cancer.

The association between statin use and prognosis in esophageal cancer patients: A meta-analysis.

The impact of statin use on the survival of esophageal cancer patients remains unclear now. The aim of this study was to identify the relationship between statin use and the long-term survival of esophageal cancer patients. The PubMed, EMBASE, and Web of Science databases were searched up to August 20, 2022, for relevant studies. The endpoints included overall survival (OS), cancer-specific survival (CSS), recurrence-free survival, and hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were pooled to assess the association between statin use and the prognosis of esophageal cancer patients. Subgroup analysis based on the pathological type (adenocarcinoma vs squamous cell carcinoma), dose of statin use and tumor stage (tumor-node-metastasis I-III vs IV) was further performed. All statistical analyses were conducted using STATA 12.0 software. A total of 7 retrospective studies involving 25,711 participants were included in this meta-analysis. The pooled results indicated that statin use was significantly associated with improved OS (HR = 0.80, 95% CI: 0.74-0.87, P < .001), CSS (HR = 0.77, 95% CI: 0.74-0.89, P < .001), and recurrence-free survival (HR = 0.38, 95% CI: 0.16-0.87, P = .022). Furthermore, subgroup analysis stratified by the pathological type, dose of statin use and tumor stage for OS and CSS showed similar results and indicated the protective role of statin use in the prognosis of esophageal cancer patients. Statin use is significantly associated with improved long-term survival of esophageal cancer patients and might serve as a promising prognostic indicator in esophageal cancer. However, more prospective high-quality studies are still needed to verify our findings.

Sarcopenia and Patient’s Body Composition: New Morphometric Tools to Predict Clinical Outcome After Ivor Lewis Esophagectomy: a Multicenter Study

BackgroundThe impact of preoperative body composition as independent predictor of prognosis for esophageal cancer patients after esophagectomy is still unclear. The aim of the study was to explore such a relationship. MethodsThis is a multicenter retrospective study from a prospectively maintained database. We enrolled consecutive patients who underwent Ivor-Lewis esophagectomy in four Italian high-volume centers from May 2014. Body composition parameters including total abdominal muscle area (TAMA), visceral fat area (VFA), and subcutaneous fat area (SFA) were determined based on CT images. Perioperative variables were systematically collected. ResultsAfter exclusions, 223 patients were enrolled and 24.2% had anastomotic leak (AL). Sixty-eight percent of patients were sarcopenic and were found to be more vulnerable in terms of postoperative 90-day mortality (p = 0.028). VFA/TAMA and VFA/SFA ratios demonstrated a linear correlation with the Clavien-Dindo classification (R = 0.311 and 0.239, respectively); patients with anastomotic leak (AL) had significantly higher VFA/TAMA (3.56±1.86 vs. 2.75 ± 1.83, p = 0.003) and VFA/SFA (1.18±0.68 vs. 0.87 ± 0.54, p = 0.002) ratios. No significant correlation was found between preoperative BMI and subsequent AL development (p = 0.159). Charlson comorbidity index correlated significantly with AL (p = 0.008): these patients had a significantly higher index (≥ 5). ConclusionAnalytical morphometric assessment represents a useful non-invasive tool for preoperative risk stratification. The concurrent association of sarcopenia and visceral obesity seems to be the best predictor of AL, far better than simple BMI evaluation, and potentially modifiable if targeted with prehabilitation programs.

Plasma microRNA-192-5p can predict the response to neoadjuvant chemotherapy and prognosis in esophageal cancer.

Esophageal cancer (EC) is the sixth leading cause of cancer-related death worldwide. Recently, neoadjuvant chemotherapy (NAC) before curative surgery has become a standard treatment for clinical stage II or III EC patients. Some EC patients receive a complete response (CR) by NAC; thus, curative surgery may be unnecessary for such patients. MicroRNA levels in plasma have the potential to be a predictor of response to NAC. In the present study, we focused on miR-192-5p, which is highly expressed in EC tissue. The purpose was to investigate the correlations between levels of plasma miR-192-5p and the response to NAC. Furthermore, molecular functions of miR-192-5p associated with chemosensitivity were examined using EC cell lines. The levels of miR-192-5p in plasma before surgery were evaluated in 113 EC patients. Sixty-nine patients received NAC. miR-192-5p levels in the CR group were significantly higher than in the other groups (p=0.002). The downregulation of miR-192-5p in the EC cell line inhibited sensitivity to cisplatin, and the overexpression of miR-192-5p in the EC cell line promoted sensitivity to cisplatin. miR-192-5p regulated sensitivity to cisplatin by targeting ERCC3 and ERCC4. Plasma miR-192-5p could be used as a predictor of response to chemotherapy and prognosis in EC patients.

Identification of the miRNA-mRNA regulatory network associated with radiosensitivity in esophageal cancer based on integrative analysis of the TCGA and GEO data

BackgroundThe current study set out to identify the miRNA-mRNA regulatory networks that influence the radiosensitivity in esophageal cancer based on the The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases.MethodsFirstly, esophageal cancer-related miRNA-seq and mRNA-seq data were retrieved from the TCGA database, and the mRNA dataset of esophageal cancer radiotherapy was downloaded from the GEO database to analyze the differential expressed miRNAs (DEmiRNAs) and mRNAs (DEmRNAs) in radiosensitive and radioresistant samples, followed by the construction of the miRNA-mRNA regulatory network and Gene Ontology and KEGG enrichment analysis. Additionally, a prognostic risk model was constructed, and its accuracy was evaluated by means of receiver operating characteristic analysis.ResultsA total of 125 DEmiRNAs and 42 DEmRNAs were closely related to the radiosensitivity in patients with esophageal cancer. Based on 47 miRNA-mRNA interactions, including 21 miRNAs and 21 mRNAs, the miRNA-mRNA regulatory network was constructed. The prognostic risk model based on 2 miRNAs (miR-132-3p and miR-576-5p) and 4 mRNAs (CAND1, ZDHHC23, AHR, and MTMR4) could accurately predict the prognosis of esophageal cancer patients. Finally, it was verified that miR-132-3p/CAND1/ZDHHC23 and miR-576-5p/AHR could affect the radiosensitivity in esophageal cancer.ConclusionOur study demonstrated that miR-132-3p/CAND1/ZDHHC23 and miR-576-5p/AHR were critical molecular pathways related to the radiosensitivity of esophageal cancer.

A bioinformatics analysis for diagnostic roles of the E2F family in esophageal cancer.

Esophageal cancer (EC) is the eighth most commonly occurring cancer worldwide and the sixth leading cause of cancer-related deaths. The therapeutic effect of EC patients is not ideal, and new biomarkers are needed to guide diagnosis and prognosis of EC patients. E2F family transcription factors are among the most important links in the cell cycle regulatory network. E2Fs dysregulation not only promotes the early stages of tumor development but also the progression of benign tumors to malignant tumors. E2F is expected to be a new biomarker. The prognostic significance of the E2F family in EC requires further research. We analyzed The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA), and GeneMANIA databases to obtain RNA-sequencing data and clinical data. The clinical data included age, gender, race, stage, type, status, etc. The prognosis outcome included overall survival (OS) and progression-free interval (PFI). Subsequently, we conducted further research on gene expressions, enrichment analysis, interaction network, and prognostic values by R software, containing ggplot2, ComplexHeatmap, DESeq2, pROC R package, based on t-test, Wilcoxon rank sum test, Spearman rank correlation analysis, log-rank test and COX model. We found that mRNA transcription levels of E2F1, E2F3-8 were more highly expressed in esophageal carcinoma (ESCA) tissues than in normal tissues. E2F8 expression was correlated with tumor stage [Pr(>F)=0.00856]. E2F-related genes played a role in development and differentiation, and were prevalent in the endoplasmic reticulum lumen, Golgi lumen, and lipoprotein particle, catalyzing translation activities and lipid metabolism. Each gene was found to be related to each other to some degree. The GeneMANIA network analysis revealed links between E2Fs and other genes. We compared the correlations between 24 kinds of tumor-infiltrating immune cells and E2Fs. E2F1 (AUC =0.945, CI: 0.890-1.000) and E2F7 (AUC =0.958, CI: 0.920-0.996) exhibited higher predictive power accuracy. However, only E2F7 was closely related to OS [HR =1.91 (1.16-3.16), P=0.011]. We discover that E2F7 is a prognostic biomarker. E2F family may take part in the development of EC through lipid metabolism pathways, which is helpful to predict the prognosis of EC patients and guide accurate diagnosis and treatment.

250. PROGNOSTIC FACTORS ASSOCIATED WITH 18FDG-PET/CT IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA AFTER TRIMODALITY TREATMENT

Abstract Patients with locally advanced and potentially curable esophageal cancer (EC) should receive trimodality treatment, which involves neoadjuvant concurrent chemoradiotherapy (nCRT) followed by esophagectomy. The maximum standard uptake value (SUVmax) in SUV of 18FDG-PET/CT have been reported to be useful in predicting the prognosis of EC patients treated with nCRT and subsequent esophagectomy. We aimed to determine the pathological response in patients with EC after trimodality therapy and to investigate the prognostic factors associated with SUVmax. This was a retrospective study of patients with locally advanced esophageal squamous cell carcinoma who received nCRT followed by esophagectomy between January 2011 and December 2018 at the Tri-Service General Hospital in Taipei, Taiwan. Survival analysis was performed using the Kaplan–Meier method and the Cox proportional hazards model. Univariate and multivariate analyses were used to determine the independent prognostic factors. A total of 79 patients with esophageal cancer underwent esophagectomy, and 50 of them were enrolled in the study. Among the 50 patients enrolled, 18 had a pCR. A post-nCRT maximum standard uptake value (SUVmax) ≥ 3 was a poor prognostic factor associated with OS (hazard ratio [HR]: 3.665, P = 0.013) and PFS (HR: 3.417, P = 0.011). Poor prognosis was found in patients with pCR and a post-nCRT SUVmax ≥3 as compared with those with pathological partial response and a post-nCRT SUVmax &amp;lt;3. SUVmax ≥3 is a poor prognostic factor in ESCC after trimodality treatment, even in patients with pCR.

Prognostic and clinicopathological value of Twist expression in esophageal cancer: A meta-analysis.

BACKGROUNDTwist is a repressor of E-cadherin transcription that induces epithelial-mesenchymal transition and cancer metastasis. However, the prognostic value of Twist expression in patients with esophageal cancer remains controversial.AIMTo investigate the prognostic and clinicopathological value of Twist expression in esophageal cancer.METHODSPublished literature in databases such as EMBASE, Web of Science, PubMed, China National Knowledge Infrastructure, Wanfang, and VIP databases was searched for eligible articles. Participants with esophageal cancer whose tumor tissues underwent immunohistochemistry to detect the expression of Twist were considered. Our meta-analysis was conducted using Stata version 12.0. The hazard ratio (HR) and relative ratio (RR) with their 95%CI were pooled. Heterogeneity was estimated by I2 statistics.RESULTSEleven articles published between 2009 and 2021 fulfilled the selection criteria. The pooled HR for overall survival was 1.88 (95%CI: 1.32-2.69, I2 = 68.6%), and the pooled HR for disease-free survival/relapse-free survival/progression-free survival was 1.84 (95%CI: 1.12-3.02, I2 = 67.1%), suggesting that high Twist expression is associated with poor prognosis in esophageal cancer patients. In addition, overexpression of Twist was correlated with T stage (T3 + T4 vs T1 + T2, RR = 1.38, 95%CI: 1.14-1.67), lymph node metastasis (yes vs no, RR = 1.34, 95%CI: 1.11-1.60), distant metastasis (yes vs no, RR = 1.18, 95%CI: 1.02-1.35), tumor, node and metastasis (TNM) stage (III + IV vs I + II, RR = 1.35, 95%CI: 1.14-1.60), and clinical stage (III + IV vs I + II, RR = 1.58, 95%CI: 1.34-1.87). However, no correlation between Twist expression and age, gender, tumor location, differentiation, or venous invasion was observed.CONCLUSIONHigh expression of Twist is associated with poor esophageal cancer prognosis. Moreover, Twist overexpression is correlated with T stage, lymph node metastasis, distant metastasis, TNM stage, and clinical stage, which indicates that Twist might accelerate esophageal cancer progression and metastasis.