Esophageal Squamous Cell Carcinoma Group Research Articles

Lipid Identification of Biomarkers in Esophageal Squamous Cell Carcinoma by Lipidomic Analysis

Lipids participate in many important biological functions through energy storage, membrane structure stabilization, signal transduction, and molecular recognition. Previous studies have shown that patients with esophageal squamous cell carcinoma (ESCC) have abnormal lipid metabolism. However, studies characterizing lipid metabolism in ESCC patients through lipidomics are limited. Plasma lipid profiles of 65 ESCC patients and 42 healthy controls (HC) were characterized by lipidomics-based ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Single-factor and multi-factor statistical analysis were used to screen the differences in blood lipids between groups, and combined with component ratio analysis and receiver operating characteristic (ROC) curve diagnostic efficiency assessment, to reveal the potential mechanisms and biomarkers of ESCC. There were significant differences in lipid profiles between the ESCC and HC groups. Thirty-six differential lipids (11 up-regulated and 25 down-regulated) were selected based on the criteria of p < .05 and fold change > 1.3 or < 0.77. Glycerophospholipids were the major differential lipids, suggesting that these lipid metabolic pathways exhibit a significant imbalance that may contribute to the development of esophageal squamous cell carcinoma. Among them, the seven candidate biomarkers for esophageal squamous cell carcinoma with the highest diagnostic value are three phosphatidylserine (PS), three fatty acids (FA) and one phosphatidylcholine (PC).

VEGF, HIF-1α, and Metabolic Indicators in Esophageal Squamous Cell Carcinoma

Objective: To explore and analyze the expression and clinical significance of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1α (HIF-1α), and metabolic indicators in esophageal squamous cell carcinoma (ESCC). Methods: Sixty ESCC patients admitted to the hospital from October 2021 to October 2023 were selected as the ESCC group. Sixty normal healthy patients from the same period were chosen as the control group. Their serum samples and tissue samples were collected. Metabolic indicators of all study subjects were obtained based on the basic biochemical results upon admission. RT-PCR was utilized to detect the expression of VEGF and HIF-1α in ESCC tissues. Results: The expression of VEGF and HIF-1α in the ESCC T3+T4 group was significantly higher than that of the carcinoma in situ (Tis) group, T1+T2 group, and control group. Furthermore, the expression of HIF-1α was found to be related to the expression of VEGF, showing a significant correlation between the quantities. Significant differences in the levels of metabolic indicators were observed between the ESCC group and the control group (P &lt; 0.05). Conclusion: Metabolic indicators are associated with the onset of ESCC in patients. Abnormal lipid metabolism plays a crucial role in the occurrence and development of tumors. The expression of VEGF and HIF-1α in ESCC tissues significantly correlates with the tumor stage, providing a new reference for the diagnosis and treatment of ESCC.

Efficacy and toxicity of anlotinib plus camrelizumab versus anlotinib plus S-1 as second-line therapy for advanced esophageal squamous cell carcinoma: A real-world retrospective study

BackgroundNo data exist on the efficacy and safety of anlotinib plus camrelizumab doublet as second-line therapy for advanced esophageal squamous cell carcinoma (ESCC). Although anlotinib and the programmed death-1 (PD-1) inhibitor camrelizumab are used as treatments for ESCC, the combined use of anlotinib and camrelizumab as a second-line therapy has not been reported. Therefore, this study explored the efficacy and toxicity of anlotinib plus camrelizumab as second-line therapy for advanced ESCC. MethodsFifty-eight patients with advanced ESCC undergoing second-line therapy, either with anlotinib plus camrelizumab or anlotinib plus S-1, were enrolled and retrospectively analyzed at Jiangsu Province Hospital of Chinese Medicine from January 2020 to December 2021. The primary endpoint was progression-free survival (PFS), with secondary endpoints including the objective response rate (ORR), disease control rate (DCR), and assessment of toxicity. ResultsIn patients with advanced ESCC, the anlotinib plus camrelizumab group exhibited longer PFS (8.00 vs. 4.53 months, P < 0.001), higher ORR ( 28.1 vs. 19.2%, P = 0.431), and higher DCR (87.5 vs. 65.4%, P = 0.045) than in the anlotinib plus S-1 group. Treatment-related adverse events (TRAEs) were predominantly grade 1/2 in both groups, with a higher incidence of grade 1/2 skin toxicity in patients treated with anlotinib plus camrelizumab (P = 0.034). Two patients (6.3%) developed grade 1/2 immune-related pneumonia. The incidence of grade 3/4 TRAEs did not differ significantly between the two groups. Multivariable Cox regression analysis identified that the drug regimen (P < 0.001), Eastern Cooperative Oncology Group performance status (P = 0.008), and differentiation grade (P = 0.008) were independent prognostic factors for PFS. ConclusionsAnlotinib plus camrelizumab exhibited promising antitumor efficacy and manageable toxicity when used as a second-line treatment for advanced ESCC.

Diagnostic performance of anti-MAGEA family protein autoantibodies in esophageal squamous cell carcinoma

MAGEA family proteins are immunogenic and can produce corresponding autoantibodies, and we aim to evaluate the diagnostic value of anti-MAGEA family protein autoantibodies in esophageal squamous cell carcinoma (ESCC). Protein chip was used to detect the expression level of anti-MAGEA autoantibodies (IgG and IgM) in 20 mixed serum samples. Enzyme linked immunosorbent assay was adopted to determine the expression level of autoantibodies in 1019 serum samples (423 ESCC, 423 healthy control (HC), 173 benign esophageal disease (BED)), and stepwise logistic regression analysis was used for developing a diagnostic model. Eight anti-MAGEA autoantibodies were screened out based on the protein chip. The levels of 7 autoantibodies (MAGEA1-IgG, MAGEA3-IgG, MAGEA3-IgM, MAGEA4-IgG, MAGEA6-IgG, MAGEA10-IgG, MAGEA12-IgG) in ESCC were significantly higher than that in HC, and the levels of anti-MAGEA1 IgG, anti-MAGEA3-IgG, anti-MAGEA4-IgG, anti-MAGEA10-IgG and anti-MAGEA12-IgG autoantibodies in ESCC group were significantly higher than those in BED group. The area under curve (AUC), sensitivity and specificity of the logistic regression model (MAGEA1-IgG, MAGEA4-IgG, MAGEA6-IgG, MAGEA12-IgG) in the training set and the validation set were 0.725 and 0.698, 55.2% and 51.8%, 80.4% and 84.5%, respectively, in distinguishing ESCC and HC. The model also could distinguish between ESCC and BED, with the AUC of 0.743, sensitivity of 55.4% and specificity of 89.0%. The positive rate of the model combined with cytokeratin 19 fragment to diagnose ESCC reached 78.0%. The study identified anti-MAGEA autoantibodies with potential diagnostic value for ESCC, which may provide new promising for the detection of the disease.

Non-acid reflux and esophageal dysmotility is associated with early esophageal squamous cell carcinoma.

Studies have demonstrated that non-acid reflux (NAR) is associated with esophageal squamous cell carcinoma (ESCC). Esophageal dysmotility is associated with NAR but few studies have focused on the esophageal motility of ESCC patients. We explored the relationship between ESCC, NAR and esophageal dysmotility with the aid of multichannel intraluminal impedance and pH (MII-pH) and high-resolution manometry (HRM). From Jan 2021 to Oct 2022, 20 patients with superficial ESCC were enrolled as the ESCC group, while 20 age and gender matched individuals without gastroesophageal reflux disease (GERD) symptoms and 20 age and gender matched patients with GERD symptoms were recruited as the control groups. Patients received 24h MII-pH and HRM procedure before endoscopic submucosal dissection (ESD), and the data were then collected to identify the type of reflux and esophageal dysmotility. Prevalence of esophageal dysmotility was significantly different among the three groups, 75.0% in the ESCC group, 35.0% in the non-GERD group and 70.0% in the GERD group (P = 0.029). NAR episodes at 15cm above the lower esophageal sphincter (LES) in the ESCC group were significantly higher than that in the non-GERD group (6.5 (3.5-9.3) vs 1.0 (0.8-4.0), P = 0.001) and were similar with that in the GERD group (6.5 (3.5-9.3) vs 5.5 (3.0-10.5), P > 0.05). NAR episodes at 5cm above LES was significantly higher in the ESCC group than that in the non-GERD group (38.0 (27.0-60.0) vs 18.0 (11.8-25.8), P = 0.001) and was significantly higher than that in the GERD group (38.0 (27.0-60.0) vs 20.0 (9.8-30.5)), P = 0.010). Prevalence of pathologic non-acid reflux was significantly different among the three groups, 30.0% in the ESCC group, 0.0% in the non-GERD group and 10.0% in the GERD group (P < 0.001). Our study found NAR and esophageal dysfunction frequently occur in ESCC patients. NAR and esophageal dysmotility may be associated with ESCC. ChiCTR2200061456.

Microbial and epidemiological factors in early detection of esophageal squamous cell carcinoma and precancerous lesions.

Microbial and epidemiological factors in early detection of esophageal squamous cell carcinoma and precancerous lesions.

Clinical and Prognostic Impact of the Warburg Effect in Esophageal Carcinoma: Monocarboxylate Transporters as Candidates for Therapeutic Targeting

Introduction: Esophageal cancer (EC) seems to display increased glycolytic activity, but clinical studies on the expression/prognostic significance of glycometabolism-related proteins, as well as functional assays, are missing. Methods: Expression of 10 glycolytic biomarkers was evaluated by immunohistochemistry in tissue sections from 95 patients. Two esophageal squamous cell carcinoma (ESCC) cell lines were used to assess the effect of monocarboxylate transporter (MCT) downregulation on cell viability and extracellular lactate/glucose accumulation. Results: Expression of MCT1, MCT4, CD147, and GLUT1 was significantly associated with an ESCC histopathology, while a poor clinicopathological profile was seen in GLUT1- and LDHA-positive EC cases. In the ESCC group, MCT1 immunoreactivity is associated with high TNM stage and metastasis. The 3-year overall survival (OS) rate was significantly influenced by MCT4 and CAIX positivity and HKII negativity. Those biomarkers were considered independent prognostic factors of OS in multivariate analysis. Dual inhibition of MCT1/4 expression decreased cell viability and extracellular lactate accumulation in ESCC cells. Conclusion: Elevated glycolytic rates correlate with a poor clinicopathological profile in EC patients. MCT4 and CAIX positivity independently predict a worse prognosis. Due to the lack of information on treatment modalities, we could not further infer the role of these biomarkers in predicting response to therapy, which needs to be assessed in future studies. In addition, MCT1/4 targeting should be performed both “in vitro” and “in vivo” to further explore its impact on tumor growth and response to classical therapies. HKII expression and function, particularly in the tumor stroma, should be investigated.

Oral microbiota may predict the presence of esophageal squamous cell carcinoma.

Microbial imbalances have been well elucidated in esophageal adenocarcinoma (EAC), but few studies address the oral microbiota in esophageal squamous cell carcinoma (ESCC). In view of the fact, we aimed to explore the associations of oral microbiota with these patients suffering from ESCC. In our study, a total of 109 individuals were enrolled (control = 53, ESCC = 56). We profiled the microbiota in oral swabs from individuals with control (ConT) and ESCC (ESCCT). 16S rRNA gene sequencing was applied to analyze the microbiome. The α and β diversity differences were tested by Tukey Test and Partial Least Squares Discriminant Analysis (PLS-DA) respectively. Linear discriminant analysis effect size (LEfSe) analysis was performed to assess taxonomic differences between the two groups. Our results showed that the microbial richness and diversity was a slightly higher in ESCCT groups than that in ConT groups. Bacteroidota, Firmicutes, Proteobacteria, Fusobacteria, Actinobacteria and Patescibacteria were the six dominant bacteria of oral flora in the two groups. When compared with control group, increased Fusobacterioa at phylum level, Neisseriaceae at family level and Leptotrichia at genus level were detected. LEfSe analysis indicated a greater abundance of Leptotrichiaceae, Leptotrichia, Fusobacteriales, Fusobacteria and Fusobacteriota in ESCC groups. Our study suggests a potential association between oral microbiome dysbiosis and ESCC and provides insights on a potential screening marker for esophageal cancer.

Risk Factors for Esophageal Squamous Cell Carcinoma in Patients with Head and Neck Squamous Cell Carcinoma

Background Esophageal squamous cell carcinoma (ESCC) is a common second primary neoplasia in patients with a history of head and neck squamous cell carcinoma (HNSCC). The aim of this study was to provide further information and novel insights into the risk factors for ESCC in patients with HNSCC. Methods We retrospectively analyzed 98 HNSCC patients diagnosed from 2007 to 2017, 30 HNSCC patients suffering from ESCC, who had undergone endoscopic examination because of positive imaging examinations or symptoms, and 68 HNSCC patients who had no ESCC occurrence for at least six years post-HNSCC diagnosis. Associated clinicopathological data and lifestyle information of the ESCC group and the without ESCC group were collected, and a case-control study of risk factors was analyzed between the two groups. Results The majority (83.4%) of the cases with HNSCC esophageal cancers were male patients over 50 years. We established that 93.75% (30/32) of the ESCC occurred within six years after HNSCC diagnosis. HNSCC location, stage, and radiotherapy history had no significant association with the development of ESCC. High Ki67 labeling index (Ki67 LI) (>46) patients tended to be 3.1 times (95% CI = 1.3–7.6) more likely to develop ESCC compared to low Ki67 LI (≤45) patients (P < 0.05). Drinkers with alcohol flushing response were at a 3.3 times higher risk to have ESCC (95% CI = 1.0–10.4) than drinkers without flush response (P < 0.05). Conclusions HNSCC patients, especially drinkers with an alcohol flushing response, as well as those with high Ki67 LI of HNSCC tissue, were more likely to develop ESCC.

Co-expression of High-mobility group box 1 protein (HMGB1) and receptor for advanced glycation end products (RAGE) in the prognosis of esophageal squamous cell carcinoma

Esophageal cancer is a malignant type of cancer with a high mortality rate. The aim of this study is to determine co-expression patterns of High-mobility group box 1 protein (HMGB1) and receptor for advanced glycation end products (RAGE) in ESCC (esophageal squamous cell carcinoma) conditions and their prognostic role in cancer progression. The expression of HMGB1 and RAGE in ESCC tissues has been analyzed using qRT–PCR and Western blotting. Co-localized expression patterns of HMGB1 and RAGE in ESCC tissues were determined using immunohistochemistry and analyzed for clinical-pathological parameters. Overall survival was performed based on co-expression of HMGB1 and RAGE proteins. A higher expression pattern of HMGB1, and RAGE was observed at mRNA and protein level in the ESCC group compared to the adjacent tissue group. Expression of HMGB1 was significantly correlated with lymph node, metastasis, lymphatic invasion, and venous invasion (p < 0.05). RAGE expression exhibited a significant correlation with venous invasion. Overall survival was significantly shorter (P < 0.05) in the patients with co-expression of HMGB1 and RAGE compared to the patients without co-expression. A significant difference in the overall survival was evident between the patients with co-expression of HMGB1 and RAGE and the patients without coexpression. HMGB1 and RAGE expression patterns were associated with aggressive metastatic characteristics of ESCC. The co-expression of HMGB1 and RAGE was correlated with shorter survival times. Results concluded the co-expression patterns of HMGB1 and RAGE exhibited a prognostic relevance in ESCC conditions.

Microbiome associations between esophageal adenocarcinoma and esophageal squamous cell carcinoma.

e16050 Background: Microbiomes in tumor environment are thought to be associated with outcomes of precision therapy. Esophageal squamous cell carcinoma (ESCC) and Eophageal adenocarcinoma (EA) are the two subtypes of esophageal cancer. Although gene mutation and expression profiles have been well characterized, the microbial set between them are poorly studied. Methods: The microbial dataset of the identified species and their relative abundance using whole genome sequencing (WGS) and whole exome sequencing (WES) was obtained from TCMA database, which includes 17 EA samples and 32 ESCC samples. To investigate the microbial difference between EA and ESCC, The alpha diversity (Shanno and Simpson index) and beta diversity (PCoA, NMDS, Adonis) were calculated using the identified species to examine the overall difference between the two subtypes. The student's t-test were used to examine the relative abundance of single species Using the identified differential abundant microbial species, correlation analysis were performed to investigate whether synergistic effects exist for some species between the two subtypes. Moreover, taxonomy set enrichment analysis was used to find out whether the differential genus between EA and ESCC were associated with cancers. Finally, cox regression was used to investigated differential species between EA and ESCC affected the survival rate of EA group or ESCC group. Results: Through alpha and beta diversities, we didn’t find overall difference between EA and ESCC both in WGS and WES datasets. However, seventeen and two differential abundance species were found using Student’s t-test in WGS and WES datasets, respectively. The relative abundances of the differential species were mostly higher in ESCC than in EA. Correlation analyses showed that prevotella sp. HMSC069G02 and prevotella sp. HMSC077E08 were highly correlated. There were eight differential species ( prevotella aurantiaca, prevotella dentalis, prevotella marshii, etc.) were found in WGS and two species ( prevotella sp. C561, prevotella pleuritidis) in WES, respectively. The ten species all belong to prevotella genus, and taxon set enrichment analysis showed prevotella genus was associated with esophageal cancer, implies the identified differential species may be different in ESCC and EA patients. Among them, prevotella dentalis and prevotella buccae were found to be potentially risk factors in ESCC after Cox regression. Conclusions: This study investigated the microbiome difference between EA and ESCC cancers. Although we didn’t find the overall difference between the two subtypes, our preliminary results showed there exist some differential species between two subtypes. We found prevotella dentalis and prevotella buccae were the potential risk factors in ESCC, and the results can help further understand the therapy outcome differences between EA and ESCC from the microbial aspect.

Characteristics of Oral Microbiota in Patients with Esophageal Cancer in China.

Gut microbiota dysbiosis is closely associated with intestinal carcinogenesis, but the oral microbiota of patients with esophageal squamous cell carcinoma who live in high-risk regions in China has not been fully characterized. In the current study, oral microbial diversity was investigated in 33 patients with esophageal squamous cell carcinoma and 35 healthy controls in Chongqing, China, by sequencing 16S rRNA of V3-V4 gene regions. There were statistically significant differences in oral microbiota between esophageal squamous cell carcinoma patients and controls as determined via unweighted pair-group analysis with arithmetic means. At the phylum level, in esophageal squamous cell carcinoma patients, there were comparatively greater amounts of Firmicutes (34.0% vs. 31.1%) and Bacteroidetes (25.3% vs. 24.9%) and lower amounts of Proteobacteria (17.0% vs. 20.1%). At the genus level, esophageal squamous cell carcinoma patients exhibited comparatively greater amounts of Streptococcus (17.3% vs. 14.5%) and Prevotella_7 (8.6% vs. 8.5%) and lower amounts of Neisseria (8.1% vs. 10.7%). Using a linear discriminant analysis effect size method, Planctomycetes and Verrucomicrobia were identified in the esophageal squamous cell carcinoma group. 10 genera were higher abundances identified in the healthy control group, and different 10 genera were identified in the esophageal squamous cell carcinoma group. In the present study, there were significant differences in oral microbial compositions of esophageal squamous cell carcinoma patients and healthy controls. Further longitudinal and mechanistic studies are needed to further characterize relationships between oral microbiota and esophageal squamous cell carcinoma.

Characterization of Esophageal Microbiota in Patients With Esophagitis and Esophageal Squamous Cell Carcinoma.

Microbial imbalances have been well elucidated in esophageal adenocarcinoma. However, few studies address the microbiota in esophageal squamous cell carcinoma (ESCC) and esophagitis (ES). We aimed to explore the association of esophageal microbiota with these patients. Esophageal tissues were obtained from healthy controls and ES and ESCC patients undergoing upper endoscopy. 16S rRNA gene sequencing was applied to analyze the microbiome. The α and β diversity differences were tested by Tukey test and partial least squares-discriminant analysis (PLS-DA), respectively. Linear discriminant analysis effect size (LEfSe) analysis was performed to assess taxonomic differences between groups. A total of 68 individuals were enrolled (control = 21, ES = 15, ESCC = 32). Microbial diversity was significantly different between the ESCC patients and healthy controls by Chao1 index, Shannon index, and PLS-DA. Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, and Fusobacteria were the five dominant bacterial phyla among the three groups. Megamonas, Collinsella, Roseburia, and Ruminococcus_2 showed a significantly continuous decreasing trend from the control group to the ESCC group at the genus level. When compared with the control group, decreased Fusobacteria at phylum level and Faecalibacterium, Bacteroides, Curvibacter, and Blautia at genus level were detected. ESCC samples also displayed a striking reduction of Bacteroidetes, Faecalibacterium, Bacteroides, and Blautia in comparison with the ES patients. LEfSe analysis indicated a greater abundance of Streptococcus, Actinobacillus, Peptostreptococcus, Fusobacterium, and Prevotella in the ESCC group. Our study suggests a potential association between esophageal microbiome dysbiosis and ESCC and provides insights into potential screening markers for esophageal cancer.

Development and Evaluation of Serum CST1 Detection for Early Diagnosis of Esophageal Squamous Cell Carcinoma.

PurposeOur pilot study has shown that cystatin SN (CST1) protein is highly expressed in esophageal squamous cell carcinoma (ESCC) tissues. We intend to develop a chemiluminescent enzyme immunoassay (CLEIA) available for serum CST1 detection and define the diagnostic value of CST1 detection for early ESCC patients, and establish a panel of CST1 with traditional tumor markers to improve the diagnostic sensitivity for early ESCC.MethodsDetection performance of CLEIA for CST1 was evaluated by linearity, detection limit, accuracy, precision, anti-interference and stability. Diagnostic performance of CST1 for early ESCC was evaluated by detecting CST1 of 112 early ESCC, 107 esophageal benign lesions (EBL), and 151 healthy controls (HC). CEA, CYFRA21-1 and SCC-Ag were detected by chemiluminescence immunoassay (CLIA).ResultsThe linear range and detection limit of CLEIA for CST1 were 6.25–400 pg/mL and 1.35 pg/mL, respectively; the average recovery rate was 102.65%; CVs of intra-batch precision and inter-batch precision were <1/4 TEa and <1/3 TEa, respectively; 8 interferents including 7 common interferents and CST4 had no interference on CST1 detection; stability evaluation showed good sample and reagent stability. The level and positive rate of CST1 in early ESCC group were significantly higher than those in EBL/HC groups (P<0.05). The diagnostic sensitivity of CST1 for early ESCC was 31.25% (specificity 92.64%, AUC 0.654). The diagnostic sensitivity of traditional tumor markers ranged from 16.07% to 28.57%, at >93.0% specificity, and SCC-Ag showed the highest AUC (0.709). Combination of CST1 and CEA, SCC-Ag exhibited the highest AUC up to 0.736 (sensitivity 49.11%, specificity 89.53%).ConclusionCLEIA has excellent detection performance for CST1. CST1 might be a prospective serological biomarker for early diagnosis of ESCC, while combination of CST1 and CEA, SCC-Ag might improve the early diagnostic performance.

Frequency of Human Papillomavirus Detection in Chagasic Megaesophagus Associated or Not with Esophageal Squamous Cell Carcinoma

Background: Chagasic megaesophagus (CM) as well as the presence of human papillomavirus (HPV) has been reported as etiological factors for esophageal squamous cell carcinoma (ESCC). Objective: We assessed the prevalence of HPV DNA in a series of ESCCs associated or not with CM. Data obtained were further correlated to the pathological and clinical data of affected individuals. Methods: A retrospective study was performed on 92 formalin-fixed and paraffin-embedded tissues collected from patients referred to 3 different hospitals in São Paulo, Brazil: Barretos Cancer Hospital, Barretos, São Paulo; Federal University of Triângulo Mineiro, Uberaba, Minas Gerais; and São Paulo State University, Botucatu, São Paulo. Cases were divided into 3 groups: (i) 24 patients with CM associated with ESCC (CM/ESCC); (ii) 37 patients with ESCC without CM (ESCC); and (iii) 31 patients with CM without ESCC (CM). Detection of HPV DNA was assessed in all samples by a genotyping assay combining multiplex polymerase chain reaction and bead-based Luminex technology. Results: We identified a high prevalence of high-risk HPV in patients in the CM group (12/31, 38.8%) and CM/ESCC (8/24, 33.3%), compared to individuals in the ESCC group (6/37, 16.3%). The individuals in the groups with cancer (ESCC and CM/ESCC) had a higher frequency of HPV-16 (4/9, 44.5% and 2/8, 25.0%). The other types of high-risk HPVs detected were HPV-31, 45, 51, 53, 56, 66, and 73. We also observed in some samples HPV coinfection by more than one viral type. Despite the high incidence of HPV, it did not show any association with the patient’s clinical-pathological and molecular (TP53 mutation status) characteristics. Conclusion: This is the first report of the presence of HPV DNA in CM associated with ESCC. HPV infection was more presence in megaesophagus lesions. Further studies are needed to confirm and better understand the role of persistent HPV infection in patients with CM.

S464 Helicobacter pylori Infection and Risk of Esophageal Carcinoma: A Systematic Review and Meta-Analysis

Introduction: Helicobacter pylori (HP) is the most common cause of peptic ulcers in the gastrointestinal tract (GIT) and has been linked to various GIT malignancies, especially gastric cancer. There is little data on the association between HP infection and esophageal cancer incidence (EC). Therefore, we aimed to conduct this meta-analysis to investigate the effect of HP infection on the risk of developing esophageal cancer. Methods: We searched PubMed and the CINHAL databases for studies reporting the association between H. pylori infection and esophageal cancer from inception to September 2020. We assessed the relationship between H. Pylori infection and the incidence of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) using odds ratio (OR) and relative 95% confidence intervals (CI). Two investigators extracted the data independently, and discrepancies were resolved by discussion with a third investigator. We used RevMan Software to perform the analysis and assessed the heterogeneity using the I2 statistic. Results: This meta-analysis included 45 studies. Total HP positive cases were 311,974 and 38,188 in the ESCC and EAC group, respectively. No statistically significant difference was found between HP and ESCC (OR = 1.10, 95% CI [0.80-1.52], P = 0.55). However, according to region, the subgroup analysis revealed a significantly higher incidence of ESCC with HP (OR = 1.83, 95% CI [1.17-2.87]) for North America. There was a statistically significant reduction in EAC with HP in the overall study population (OR = 0.54, 95% CI [0.34-0.87], P = 0.01). Subgroup analysis showed that western countries were associated with statistically reduced EAC incidence (OR = 0.51, 95% CI [0.32-0.83]). On the other hand, subgroup analysis of eastern countries reported non-significant results (OR = 0.81, 95% CI [0.15-4.30]). Conclusion: Overall, no significant association was found between H. pylori infection and the risk of ESCC. There was a statistically significant reduction in EAC with HP in the overall study population. In subgroup analysis a significantly increased incidence of ESCC is seen in North America and a significantly reduced risk of EAC in western countries. Further randomized controlled trials are need to investigate the protective effect of helicobacter pylori infection for risk of esophageal adenocarcinoma.

The TP53-Related Signature Predicts Immune Cell Infiltration, Therapeutic Response, and Prognosis in Patients With Esophageal Carcinoma.

TP53 mutation (TP53MUT) is one of the most common gene mutations and frequently occurs in many cancers, especially esophageal carcinoma (ESCA), and it correlates with clinical prognostic outcomes. Nevertheless, the mechanisms by which TP53MUT regulates the correlation between ESCA and prognosis have not been sufficiently studied. Here, in the current research, we constructed a TP53MUT-related signature to predict the prognosis of patients with esophageal cancer and successfully verified this model in patients in the TP53 mutant group, esophageal squamous cell carcinoma group, and adenocarcinoma group. The risk scores proved to be better independent prognostic factors than clinical features, and prognostic features were combined with other clinical features to establish a convincing nomogram to predict overall survival from 1 to 3 years. In addition, we further predicted the tumor immune cell infiltration, chemical drugs, and immunotherapy responses between the high-risk group and low risk group. Finally, the gene expression of the seven-gene signature (AP002478.1, BHLHA15, FFAR2, IGFBP1, KCTD8, PHYHD1, and SLC26A9) can provide personalized prognosis prediction and insights into new treatments.

Development of a panel of autoantibody against NSG1 with CEA, CYFRA21-1, and SCC-Ag for the diagnosis of esophageal squamous cell carcinoma

ObjectiveDevelopment of a panel of serum autoantibody against Neuron specific gene family member 1 (NSG1) with traditional tumor biomarkers of esophageal squamous cell carcinoma (ESCC) to further improve the diagnostic efficiency for ESCC patients. MethodsImmunohistochemistry (IHC) staining was used to detect the expression of NSG1 protein in 40 pairs of ESCC tissues and matched paracancerous tissues. Serum anti-NSG1 levels of 203 patients with early ESCC, 103 patients with advanced ESCC, 135 patients with esophageal benign lesion (EBL), and 155 healthy controls (HCs) were detected by ELISA. The diagnostic performances of all possible combinations of serum anti-NSG1with CEA, CYFRA21-1 and SCC-Ag were assessed to develop an optimal panel for ESCC diagnosis. ResultsNSG1 protein expression in ESCC tissues was significantly higher than that in matched paracancerous tissues (p < 0.001). Serum anti-NSG1 expression in ESCC group was significantly higher than that in EBL group and HC group (p < 0.001). The AUC of serum anti-NSG1 for ESCC was 0.706, with 49.7% sensitivity at 93.5% specificity, superior to that of CEA, CYFRA21-1 and SCC-Ag. Of all possible combinations, serum anti-NSG1 combined with CEA, CYFRA21-1 and SCC-Ag showed the highest AUC of 0.758 and 67.3% sensitivity at 88.3% specificity for ESCC, with the highest NPV of 71.9% and the lowest NLR of 0.37. ConclusionAberrant NSG1 protein expression in ESCC tissues might be responsible for massive releases of autoantibody anginst NSG1 in sera of ESCC. A panel of anti-NSG1 with CEA, CYFRA21-1 and SCC-Ag contributes to further improving the diagnostic efficiency for ESCC.

Urinary microRNA biomarkers for detecting the presence of esophageal cancer

Esophageal cancer (EC) including esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC) generally exhibits poor prognosis; hence, a noninvasive biomarker enabling early detection is necessary. Age- and sex-matched 150 healthy controls (HCs) and 43 patients with ESCC were randomly divided into two groups: 9 individuals in the discovery cohort for microarray analysis and 184 individuals in the training/test cohort with cross-validation for qRT-PCR analysis. Using 152 urine samples (144 HCs and 8 EACs), we validated the urinary miRNA biomarkers for EAC diagnosis. Among eight miRNAs selected in the discovery cohort, urinary levels of five miRNAs (miR-1273f, miR-619-5p, miR-150-3p, miR-4327, and miR-3135b) were significantly higher in the ESCC group than in the HC group, in the training/test cohort. Consistently, these five urinary miRNAs were significantly different between HC and ESCC in both training and test sets. Especially, urinary miR-1273f and miR-619-5p showed excellent values of area under the curve (AUC) ≥ 0.80 for diagnosing stage I ESCC. Similarly, the EAC group had significantly higher urinary levels of these five miRNAs than the HC group, with AUC values of approximately 0.80. The present study established novel urinary miRNA biomarkers that can early detect ESCC and EAC.

Intravoxel Incoherent Motion Model in Differentiating the Pathological Grades of Esophageal Carcinoma: Comparison of Mono-Exponential and Bi-Exponential Fit Model.

PurposeTo compare the diagnostic efficiency of the mono-exponential model and bi-exponential model deriving from intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in differentiating the pathological grade of esophageal squamous cell carcinoma (ESCC).MethodsFifty-four patients with ESCC were divided into three groups of poorly-differentiated (PD), moderately-differentiated (MD), and well-differentiated (WD), and underwent the IVIM-DWI scan. Mono-exponential (Dmono, D*mono, and fmono) and bi-exponential fit parameters (Dbi, D*bi, and fbi) were calculated using the IVIM data for the tumors. Mean parameter values of three groups were compared using a one-way ANOVA followed by post hoc tests. The receiver operating characteristic curve was drawn for differentiating pathological grade of ESCC. Correlations between pathological grades and IVIM parameters were analyzed.ResultsThere were significant differences in fmono and fbi among the PD, MD and WD ESCC groups (all p<0.05). The fmono were 0.32 ± 0.07, 0.23 ± 0.08, and 0.16 ± 0.05, respectively, and the fbi were 0.35 ± 0.08, 0.26 ± 0.10, and 0.18 ± 0.07, respectively. There was a significant difference in the Dmono between the WD and the PD group (1.48 ± 0.51* 10-3 mm2/s versus 1.05 ± 0.44*10-3 mm2/s, p<0.05), but there was no significant difference between the WD and MD groups, MD and PD groups (all p>0.05). The D*mono, Dbi, and D*bi showed no significant difference among the three groups (all p>0.05). The area under the curve (AUC) of Dmono, fmono and fbi in differentiating WD from PD ESCC were 0.764, 0.961 and 0.932, and the sensitivity and specificity were 92.9% and 60%, 92.9% and 90%, 85.7% and 100%, respectively. The AUC of fmono and fbi in differentiating MD from PD ESCC were 0.839 and 0.757, and the sensitivity and specificity were 78.6% and 80%, 85.7% and 70%, respectively. The AUC of fmono and fbi in differentiating MD from WD ESCC were 0.746 and 0.740, and the sensitivity and specificity were 65% and 85%, 80% and 60%, respectively. The pathologically differentiated grade was correlated with all IVIM parameters (all p<0.05).ConclusionsThe mono-exponential IVIM model is superior to the bi-exponential IVIM model in differentiating pathological grades of ESCC, which may be a promising imaging method to predict pathological grades of ESCC.