High Incidence Of Esophageal Cancer Research Articles

Association of gastroesophageal reflux disease with gastritis activity in schoolchildren living in a region with a high incidence of gastric and esophageal cancer

Aim. To study the activity of the inflammatory process in the gastric mucosa (GM) in gastroesophageal reflux disease (GERD) in schoolchildren living in a region with a high incidence of stomach and esophageal cancer. Material and methods. The transverse method in the Republic of Tyva collected data on the presence of gastroenterological complaints in 1535 schoolchildren aged 7-17 years. The main diagnostic criterion for GERD was the presence of weekly heartburn in the subjects. Subsequently, esophagogastroduodenoscopy was performed with the taking of biopsy material of the mucosa of the antrum and body of the stomach in 246 children. Morphological assessment of GM was carried out in accordance with the Sydney classification after staining biopsy sections with hematoxylin-eosin. Diagnosis of Helicobacter pylori was carried out after staining according to Giemsa. The studies were approved by the ethics committee and the consent of the examined was obtained. Results. Schoolchildren in Tyva have a high prevalence of GERD (9.5%). Associative relationship of GERD with gastritis activity, both in the body (p=0.7338) and in the antrum (p=0.2036) was not revealed. In the antrum, the activity of gastritis was higher than in the body of the stomach (p=0.0001). In children with GERD, when infected with Helicobacter pylori, there was an increase in activity, both in the antrum (p=0.0001) and in the body of the stomach (p=0.0159). At the same time, in children with GERD, the inflammatory process is associated with infection by a microorganism, regardless of its belonging to the Cag A strain. Conclusion. An association of GERD with highly active Helicobacter pylori associated gastritis has been established, regardless of whether the microorganism belongs to the Cag A strain.

HOGG1: A novel mediator in nitrosamine-induced esophageal tumorigenesis

BackgroundThe effect of human 8-Oxoguanine DNA Glycosylase (hOGG1) on exogenous chemicals in esophageal squamous cell carcinoma (ESCC) remain unclear. The study plans to determine hOGG1 expression levels in ESCC and possible interactions with known environmental risk factors in ESCC. Material and methodsWe analyzed levels of exposure to urinary nitrosamines in volunteers from high and low prevalence areas by GC-MS. And we performed the interaction between hOGG1 gene and nitrosamine disinfection by-products by analyzing hOGG1 gene expression in esophageal tissues. ResultsIn ESCC, nitrosamine levels were significantly increased and hOGG1 mRNA expression levels were significantly decreased. There was a statistically significant interaction between reduced hOGG1 mRNA levels and non-tap drinking water sources in ESCC. The apparent indirect association between ESCC and NMEA indicated that 33.4% of the association between ESCC and NMEA was mediated by hOGG1. ConclusionIn populations which exposed to high levels of environmental pollutants NDMA, low expression of hOGG1 may promote the high incidence of esophageal cancer in Huai'an. hOGG1 may be a novel mediator in nitrosamine-induced esophageal tumorigenesis.

Age-period-cohort analysis of incidence, mortality and disability-adjusted life years of esophageal cancer in global, regional and national regions from 1990 to 2019

ObjectiveIn view of the high incidence and mortality of esophageal cancer, the latest statistical data on the disease burden of esophageal cancer can provide strategies for cancer screening, early detection and treatment, and help to rationally allocate health resources. This study provides an analysis of the global disease burden and risk factors of esophageal cancer from 1990 to 2019.MethodsUsing the 2019 Global Burden of Disease, Injury and Risk Factor (GBD) data, we present the incidence, mortality and disability-adjusted life years (DALY) of esophageal cancer in 21 regions and 204 countries and different sociodemographic index (SDI) regions from 1990 to 2019. The age-period-cohort model was used to estimate the age, period, and cohort trend of esophageal cancer in different SDI regions. The estimated proportion of DALY attributable to each risk factor from 1990 to 2019.ResultsFrom 1990 to 2019, the number of new cases of esophageal cancer, the number of deaths and DALY increased by 67.07%, 55.97% and 42.13%, respectively, but age standardized incidence rate (ASIR), age standardized mortality rate (ASMR) and age standardized DALY rate (ASDR) decreased by 19.28%, 25.32% and 88.22%, respectively. Overall, the results of the age-period-cohort model showed that the incidence, mortality, and DALY rates in countries and regions with higher SDI levels showed a downward trend over time and with the passage of time. Conversely, there were no significant changes in incidence and mortality in countries and regions with low SDI levels. In the past 30 years, the incidence and death of esophageal cancer in the world has gradually changed to people over 80 years old, but the population aged 60–79 still accounts for the largest proportion. The global DALY in esophageal cancer is mainly attributable to smoking, followed by alcohol consumption and occupational exposure.ConclusionsAlthough ASIR, ASMR and ASDR have decreased significantly, esophageal cancer is still the main factor causing the disease burden worldwide. Public health administrators in low SDI and low-middle SDI countries are high-risk areas for esophageal cancer, and preventive control measures should be implemented to raise awareness, screening, and treatment of esophageal cancer in these areas. Tobacco and alcohol control and reduction of occupational hazards are key steps in reducing the burden of esophageal cancer.

New hope for esophageal stricture prevention: A prospective single-center trial on acellular dermal matrix.

Given the high incidence of esophageal cancer in China, an increasing number of patients there are undergoing endoscopic mucosal dissection (ESD). Although the 5-year survival rate after ESD can exceed 95%, esophageal stricture, the most common and serious postoperative complication, affects the long-term prognosis of patients and the quality of life. Autologous mucosal grafts have proven to be successful in preventing stricture after ESD for early esophageal cancer. To examine the viability of acellular dermal matrix (ADM) as an alternative to autologous mucosa for the prevention of stricture after ESD. This is a prospective, single-center, controlled study. Consecutive patients who underwent ESD surgery and were willing to undergo autologous mucosal transplantation were recruited between January 1 and December 31, 2017. Consecutive patients who underwent ESD surgery and were willing to undergo ADM transplantation were recruited between January 1 to December 31, 2019. A final three-year follow-up of patients who received transplants was conducted. Based on the current incidence of esophageal stricture, the sample size required for both the autologous mucosal graft group and the ADM group was calculated to be 160 cases. Due to various factors, a total of 20 patients with autologous mucosal grafts and 25 with ADM grafts were recruited. Based on the inclusion exclusion and withdrawal criteria, 9 patients ultimately received autologous mucosal grafts and completed the follow-up, while 11 patients received ADM grafts and completed the follow-up. Finally, there were 2 cases of stenosis in the autologous mucosal transplantation group with a stenosis rate of 22.22% and 2 cases of stenosis in the ADM transplantation group with a stenosis rate of 18.18%, with no significant difference noted between the groups (P = 0.94). In this prospective, single-center, controlled trial, we compared the effectiveness of autologous mucosa transplantation and ADM for the prevention of esophageal stricture. Due to certain condition limitations, we were unable to recruit sufficient subjects meeting our target requirements. However, we implemented strict inclusion, exclusion, and withdrawal criteria and successfully completed three years of follow-up, resulting in valuable clinical insights. Based on our findings, we hypothesize that ADM may be similarly effective to autologous mucosal transplantation in the prevention of esophageal stricture, offering a comparable and alternative approach. This study provides a new therapeutic idea and direction for the prevention of esophageal stricture.

Smoke exposure associated with higher urinary benzene biomarker muconic acid (MUCA) in Golestan Cohort Study participants

Background. Benzene is a known human carcinogen. Human exposure to benzene can be assessed by measuring trans, trans-muconic acid (MUCA) in urine. Golestan Province in northeastern Iran has been reported to have high incidence of esophageal cancer linked to the use of tobacco products. This manuscript evaluates the urinary MUCA concentrations among the participants of the Golestan Cohort Study (GCS).Methods. We analyzed MUCA concentration in 177 GCS participants’ urine samples and performed nonparametric pairwise multiple comparisons to determine statistically significant difference among six different product use groups. Mixed effects model was fitted on 22 participants who exclusively smoked cigarette and 51 participants who were classified as nonusers. The urinary MUCA data were collected at the baseline and approximately five years later, and intraclass correlation coefficient (ICC) was calculated from the model.Results. Compared with nonusers, tobacco smoking was associated with higher urinary MUCA concentrations. Based on the nonparametric test of pairwise multiple comparisons, MUCA concentrations among participants who smoked combusted tobacco products were statistically significantly higher compared to nonusers. Urinary MUCA collected five years apart from the same individuals showed moderate reliability (ICC = 0.41), which was expected given the relatively short half-life (∼6 h) of MUCA.Conclusion. Our study revealed that tobacco smoke was positively associated with increased levels of urinary MUCA concentration, indicating that it is a significant source of benzene exposure among GCS participants.

Geographic, sex and socioeconomic disparities in esophageal cancer incidence in China: A population-based study.

Geographic and sex differences in esophageal cancer have been reported in China, but data are lacking at the local level. We aimed to investigate geographic and sex disparities in esophageal cancer incidence among Chinese counties and whether county-level socioeconomic status was associated with these variations. We obtained esophageal cancer data from 2015 to 2017 for 782 counties from population-based cancer registries in China. We calculated age-standardized incidence rates and male-to-female incidence rate ratios (IRRs) by county. We performed hotspot analysis to identify geographical clusters. We used negative binomial regression models to analyze the association between incidence rates and county-level socioeconomic factors. There were significant geographic disparities in esophageal cancer incidence, with 8.1 times higher rate in the 90th-percentile county than in the 10th-percentile county (23.7 vs 2.9 per 100 000 person-years). Clusters of elevated rates were prominent across north-central China. Nationally, men had 2.9 times higher incidence of esophageal cancer than women. By county, the male-to-female IRRs ranged from 1.1 to 21.1. Clusters of high male-to-female IRRs were observed in northeast China. Rurality (IRR 1.16, 95% CI 1.10-1.22), per capita gross domestic product (IRR 0.95, 0.92-0.98) and percentage of people with a high school diploma (IRR 0.86, 0.84-0.87) in a county were significantly associated with esophageal cancer incidence. The male-to-female IRRs were higher in counties with higher socioeconomic status. Substantial differences in incidence rates and sex ratios of esophageal cancer exist between Chinese counties, and county-level socioeconomic status was associated with these variations. These findings may inform interventions to reduce these disparities.

Environmental and life-style risk factors for esophageal squamous cell carcinoma in Africa: a systematic review and meta-analysis

BackgroundThe African Esophageal Squamous Cell Carcinoma (ESCC) corridor, which spans from Ethiopia down to South Africa, is an esophageal cancer hotspot. Disproportionately high incidence and mortality rates of esophageal cancer have been reported from this region. The aim of this study was to systematically assess the evidence on environmental and life-style risk factors associated with ESCC in African populations.MethodsWe followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and carried out a comprehensive search of all African published studies up to March 2023 using PubMed, Embase, Scopus, and African Index Medicus databases.ResultsWe identified 45 studies with measures of association [odds ratio (OR), relative risk (RR), and 95% confidence intervals (95%CI)], which reported on several environmental and lifestyle risk factors for ESCC in Africa. We performed a meta-analysis on 38 studies investigating tobacco, alcohol use, combined tobacco and alcohol use, polycyclic aromatic hydrocarbon exposure, hot food and beverages consumption (which served as a proxy for esophageal injury through exposure to high temperature), and poor oral health. We found significant associations between all the risk factors and ESCC development. Analysis of fruit and vegetable consumption showed a protective effect. Using population attributable fraction (PAF) analysis, we calculated the proportion of ESCC attributable to tobacco (18%), alcohol use (12%), combined tobacco and alcohol use (18%), polycyclic aromatic hydrocarbon exposure (12%), hot food and beverages intake (16%), poor oral health (37%), and fruit and vegetable consumption (-12%).ConclusionsTobacco smoking and alcohol consumption were the most studied risk factors overall. Areas where there is an emerging body of evidence include hot food and beverages and oral health. Concurrently, new avenues of research are also emerging in PAH exposure, and diet as risk factors. Our results point to a multifactorial etiology of ESCC in African populations with further evidence on prevention potential.

The current state of artificial intelligence in endoscopic diagnosis of early esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor of the digestive tract. The most effective method of reducing the disease burden in areas with a high incidence of esophageal cancer is to prevent the disease from developing into invasive cancer through screening. Endoscopic screening is key for the early diagnosis and treatment of ESCC. However, due to the uneven professional level of endoscopists, there are still many missed cases because of failure to recognize lesions. In recent years, along with remarkable progress in medical imaging and video evaluation technology based on deep machine learning, the development of artificial intelligence (AI) is expected to provide new auxiliary methods of endoscopic diagnosis and the treatment of early ESCC. The convolution neural network (CNN) in the deep learning model extracts the key features of the input image data using continuous convolution layers and then classifies images through full-layer connections. The CNN is widely used in medical image classification, and greatly improves the accuracy of endoscopic image classification. This review focuses on the AI-assisted diagnosis of early ESCC and prediction of early ESCC invasion depth under multiple imaging modalities. The excellent image recognition ability of AI is suitable for the detection and diagnosis of ESCC and can reduce missed diagnoses and help endoscopists better complete endoscopic examinations. However, the selective bias used in the training dataset of the AI system affects its general utility.

Fate of selenium in a Se-enriched region of North China: Translocation, bioaccumulation, source, and health benefits

There are limited studies on the translocation and bioaccumulation of selenium (Se) in weak alkaline cultivated Se-enriched soil, and the sources and speciation of Se in wheat grains remain unclear. In this study, we measured the Se levels in soils, roots, stems, and wheat grains from Se-enriched cultivated land in Ci County, China, which has a high incidence of esophageal cancer. The Se levels in the roots were higher than those in the soils, indicating that wheat plants bioaccumulated high concentrations of Se from the soil (enrichment coefficient [EC] range from the soil to the root: 0.94–3.29). Redundancy analysis indicated that the bioaccumulated factor, translocation coefficient, and EC were mainly controlled by phosphorus, pH, and Fe2O3 (contribution rates: 37.5%, 19.5%, and 15.9%, respectively). Linear regression analysis revealed that the sources of Se in grains were mainly from the water-soluble fraction (R2 = 0.55, at p < 0.05), the weakly acidic fraction (R2 = 0.84, at p < 0.05), the reducible fraction (R2 = 0.84, at p < 0.05), and the oxidizable fraction (R2 = 0.70, at p < 0.05), as well as from atmospheric deposition (R2 = 0.37, at p < 0.01). There is a significant correlation between the Se from atmospheric deposition and the oxidizable fraction (R2 = 0.62, at p < 0.01) and the residual fraction (R2 = 0.33, at p < 0.01). The contribution of Se input flux from atmospheric deposition was 5.50 g/hm2 for one year. Furthermore, the average content of organic Se in wheat grains was 58.93%. The Se concentrations found in wheat grains were considered beneficial for human health based on a comparison with the Chinese Society of Nutrition standard and worldwide levels. The results of this study will increase the overall knowledge on the theme, which could help prevent and control the harmful effects of undesirable concentrations of Se on human health.

Disparities in oesophageal cancer risk by age, sex, and nativity in Kuwait:1980–2019

BackgroundThis cross-sectional cohort study assessed the inequalities in oesophageal carcinoma risk by age, sex and nativity in Kuwait: 1980–2019.MethodsUsing oesophageal cancer incidence data from the Kuwait National Cancer Registry, relevant Kuwaiti population data and World Standard Population as a reference, age-standardized incidence rates (ASIR) (per 100,000 person-years) overall and by subcohorts were computed. The incident oesophageal cancer cases count was overdispersed with excessive structural zeros, therefore, it was analyzed using multivariable zero-inflated negative binomial (ZINB) model.ResultsOverall ASIR of oesophageal cancer was 10.51 (95% CI: 6.62-14.41). The multivariable ZINB model showed that compared with the younger age category (< 30 years), the individuals in higher age groups showed a significant (p < 0.001) increasing tendency to develop the oesophageal cancer. Furthermore, compared with the non-Kuwaiti residents, the Kuwaiti nationals were significantly (p < 0.001) more likely to develop oesophageal cancer during the study period. Moreover, compared with 1980-84 period, ASIRs steadily and significantly (p < 0.005) declined in subsequent periods till 2015-19.ConclusionsA high incidence of oesophageal cancer was recorded in Kuwait, which consistently declined from 1980 to 2019. Older adults (aged ≥ 60 years) and, Kuwaiti nationals were at high risk of oesophageal cancer. Focused educational intervention may minimize oesophageal cancer incidence in high-risk groups in this and other similar settings. Future studies may contemplate to evaluate such an intervention.

Association of gastroesophageal reflux disease with gastritis activity in schoolchildren living in a region with a high incidence of gastric and esophageal cancer

Aim. To study the activity of the inflammatory process in the gastric mucosa (GM) in gastroesophageal reflux disease (GERD) in schoolchildren living in a region with a high incidence of stomach and esophageal cancer. Material and methods. The transverse method in the Republic of Tyva collected data on the presence of gastroenterological complaints in 1535 schoolchildren aged 7-17 years. The main diagnostic criterion for GERD was the presence of weekly heartburn in the subjects. Subsequently, esophagogastroduodenoscopy was performed with the taking of biopsy material of the mucosa of the antrum and body of the stomach in 246 children. Morphological assessment of GM was carried out in accordance with the Sydney classification after staining biopsy sections with hematoxylin-eosin. Diagnosis of Helicobacter pylori was carried out after staining according to Giemsa. The studies were approved by the ethics committee and the consent of the examined was obtained. Results. Schoolchildren in Tyva have a high prevalence of GERD (9.5%). Associative relationship of GERD with gastritis activity, both in the body (p=0.7338) and in the antrum (p=0.2036) was not revealed. In the antrum, the activity of gastritis was higher than in the body of the stomach (p=0.0001). In children with GERD, when infected with Helicobacter pylori, there was an increase in activity, both in the antrum (p=0.0001) and in the body of the stomach (p=0.0159). At the same time, in children with GERD, the inflammatory process is associated with infection by a microorganism, regardless of its belonging to the Cag A strain. Conclusion. An association of GERD with highly active Helicobacter pylori associated gastritis has been established, regardless of whether the microorganism belongs to the Cag A strain.

Artemisinin inhibits the development of esophageal cancer by targeting HIF-1α to reduce glycolysis levels.

China has a high incidence of esophageal cancer (EC), mainly squamous cell carcinoma, which is a serious threat to human life. Previous studies have shown that artemisinin can inhibit the proliferation and metastasis of cancer cells, thus inhibiting the progression of cancer. Aerobic glycolysis plays an important role in the uncontrolled growth of tumor cells. However, there are still different opinions on the anti-cancer mechanism, and there have been few studies involving EC. Our pre-experiment found that artemisinin can inhibit the progression of EC by directly regulating aerobic glycolysis. The EC cell lines KYSE-150 and KYSE-170 were used to detect the effects of artemisinin on cell viability, proliferation, metastasis, and aerobic glycolysis. Network pharmacology technology was used to explore the potential molecular mechanism of artemisinin inhibiting the development of EC through aerobic glycolysis and the findings were verified by molecular docking. Artemisinin could inhibit the proliferation, metastasis, and glycolysis of esophageal squamous cell carcinoma (ESCC), and this was verified by the expression of key metastatic proteins (N-cadherin) and key enzymes of glycolysis [hypoxia-inducible factor-1α (HIF-1α), pyruvate kinase M2 (PKM2)]. Through network pharmacology, we found the potential therapeutic target of artemisinin, HIF-1α. The results of molecular docking showed that artemisinin could directly target HIF-1α and promote its degradation. Artemisinin can target HIF-1α to reduce the level of glycolysis and inhibit the development of EC, which may become a targeted drug for the treatment of EC.

297. ESOPHAGECTOMY IN ELDERLY PATIENTS WITH ESOPHAGEAL CANCER: A FIVE-YEAR EXPERIENCE FROM A CANCER CENTRE IN NORTH-EAST INDIA

Abstract North-East India has a high incidence of esophageal cancer. An elderly patient with esophageal cancer often has multiple comorbidities and compromised general condition and so, esophagectomy in this population is associated with more morbidity and mortality. Our objectives were to estimate the 30-day morbidity and mortality and estimate the disease-free and overall survival and recurrence patterns. Retrospective, observational single institute study. We included all patients with age ≥ 60 years with a proven diagnosis of esophageal cancer and who underwent an esophagectomy during the study period from 1st January 2016 to 31st December 2020. Data was collected from patient’s records and the results were presented using median values, range and percentages. There were 35 patients; median age was 65 years (range 60 to 76 years). Neoadjuvant chemotherapy (40.0%) was used more than chemoradiation (31.4%). Procedures included trans-thoracic esophagectomy (68.6%), trans-hiatal esophagectomy (25.7%) and left thoraco-abdominal approach (5.7%). 30-day mortality rate was 8.6% (aMI, COVID pneumonia and ARDS). 30-day morbidity rate was 40%, with pulmonary (25.7%), hoarseness of voice (17.1%), anastomotic leak (14.3%), wound infection (11.4%), symptomatic cardiac arrhythmias (5.7%) and septicaemia (2.9%) being part of the spectrum. 8.5% had locoregional recurrence and 5.7% had distant recurrence (peritoneum, bones and liver). Median overall survival was 33 months (range 9 to 43 months). Esophagectomy in elderly patients carry a high risk of 30-day morbidity and mortality, but has acceptable overall survival.

296. A BEGINNER’S THREE-YEAR LEARNING CURVE WITH ESOPHAGECTOMIES: A STUDY FROM A PERIPHERAL CANCER CENTRE IN NORTH-EAST INDIA

Abstract North-East India has a high incidence of esophageal cancer but lacks good infrastructure for cancer care delivery. I aim to present my experience with esophagectomies done in a cancer center of the region, as a beginner immediately after completion of broad specialty surgical oncology training. The objectives include estimation of 30-day morbidity and mortality rates and the short-term oncological outcomes including nodal yield and completeness of resection. Retrospective observational study of a prospectively maintained database, during the study period from 1st November 2018 to 31st March 2022 (29 months). All patients had confirmed diagnosis of esophageal cancer and underwent esophagectomy by the same surgeon. They received neoadjuvant treatment as per institutional protocol. The results were presented with median values, range and percentages. 46 patients underwent esophagectomy; one had inoperable disease. Clinicopathological factors are in Table 1. 74.5% had neoadjuvant chemoradiation (NACRT). Minimally invasive trans-thoracic esophagectomy (67.4%) was favoured approach (conversion rate of 6%). 41.3% had ‘extended 2-field’ lymphadenectomy. 30-day mortality was 4.2% and morbidity included hoarseness of voice (17.4%), anastomotic leak (10.9%) and pneumonia (8.7%). Median nodal yield was 12 (range 4 to 48). Pathological complete response was noted in 44.1% of post-NACRT patients. Margin-negative resection was achieved in 91.3% patients. After median follow up of 20 months, 5 locoregional and 3 distant recurrences were noted. 76.6% patients are alive without disease. Surgical audit is key at the beginning of a surgical career to gain insights into learning curve and areas of improvement include nodal yield and morbidity rates. The high margin negative resection rates are partly attributable to selection bias of a beginner.

366. SURGERY VERSUS NON-SURGICAL TREATMENT FOR THORACIC ESOPHAGEAL CANCER IN PATIENTS OLDER THAN 70 YEARS: A RETROSPECTIVE ANALYSIS OF 749 CASES

Abstract The highest incidence of esophageal cancer is in East Asia, but as for advanced age people, there are also many non-tumor factors affecting overall survival (OS), such as cardiovascular and cerebrovascular diseases. Our purpose is to determine whether the older patients after esophagectomy had better OS than those treated with non-surgical treatment. Data were obtained from the Sichuan Cancer Hospital &amp; Institute Esophageal Cancer Case Management Database (SCH-ECCM Database) and Department of Radiation Oncology Database. We retrospective analyzed esophageal cancer patients older than 70 years who underwent esophagectomy or radiotherapy/chemotherapy from Jan. 2009 to Dec. 2017. The patients were divided into two groups: surgery group (S group), and non-surgery group (NS group). Outcome measures depend on OS. After 60.6 months of median follow-up time, 749 patients were included. 532 of 749 patients (71.0%) underwent surgery, 217 of 749 patients (39.0%) underwent non-surgical treatment including radiotherapy and/or chemotherapy. In the S group, the median OS of was 39.7 months (95% CI 33.7–45.7), while the NS group was only 24.0 months (95% CI 19.6–28.4). The OS at 1, 3, and 5 years were 84%, 52%, and 39% in the S group, respectively. In the NS group, the OS rates at 1, 3, and 5 years were 72%, 32%, and 29%, respectively (HR 0.69, 95% CI 0.561–0.846, P&amp;lt;0.0001). Esophageal cancer patients older than 70 years who underwent esophagectomy had significantly better OS than those who underwent non-surgical treatment based on radiotherapy and/or chemotherapy.

Proteomic profiling of plasma exosomes reveals CD82 involvement in the development of esophageal squamous cell carcinoma

The Xinjiang Uygur autonomous region has a high incidence of esophageal cancer. For the early diagnosis of patients with esophageal squamous cell carcinoma (ESCC), exosomes were isolated and quantified by liquid chromatography tandem mass spectrometry ((LC–MS/MS) with data independent acquisition (DIA) from the peripheral blood of patients with benign esophageal disease (BED), esophageal intraepithelial neoplasia (EIN) and ESCC. A total of 1117 proteins were identified in the above 9 samples. The proteomic results showed that the quantity of CD82 in exosomes of EIN was significantly higher than that in patients with BED and ESCC. Meanwhile, our ELISA test verified our proteomic results. In addition, the immunohistochemical results showed high CD82 expression in adjacent normal tissues and low expression in ESCC tissues. CD82 expression in ESCC tissues was negatively correlated with tumor stage and the expression of PKM2, and the high expression of CD82 combined with low expression of PKM2 in ESCC tissues suggested a good prognosis. To further clarify the tumor suppressive mechanism of CD82, the TIMER and TISDB databases were analyzed, and CD82 expression in tumor tissues was found to be related to the infiltration of immune cells. CD82 in exosomes is involved in the development of ESCC. SignificanceXinjiang is a high incidence area of ESCC. When diagnosed in the middle and late stages of the disease, the prognosis of patients is poor. Exosomes provide the possibility of relatively noninvasive and early detection of esophageal carcinogenesis. To the best of our knowledge, this was the first study using the DIA technique to analyze the exosomal proteins of patients with different stages of ESCC. The proteins identified in the exosomes in these three groups could provide insights for understanding how exosomes promote the occurrence of ESCC, the antitumour mechanism of humans and the early diagnosis of ESCC.

Artesunate Inhibits the Development of Esophageal Cancer by Targeting HK1 to Reduce Glycolysis Levels in Areas With Zinc Deficiency.

Esophageal cancer (EC) threatens many lives in China, especially in areas with high incidences of EC. Our previous studies proved that zinc deficiency (ZD) promotes the cell cycle, thus promoting the progression of EC in areas with a high incidence of EC. Artesunate could inhibit the cell cycle, thereby inhibiting the progression of EC. In this study, we first demonstrated the mechanism by which artesunate inhibits EC in vitro and then demonstrated that artesunate could reverse the ZD-promoted progression of EC before EC occurred in vivo. The results showed that artesunate could inhibit the cell cycle, metastasis, and glycolysis of EC cells. Artesunate could target HK1, promote HK1 degradation, and reduce the levels of HIF-1α and PKM2 expression, which are key glycolysis enzymes. The in vivo results showed that ZD could increase the expression of HK1 and increase the incidence of EC. Artesunate reduced the incidence of EC and decreased the level of HK1 expression before EC occurred. Artesunate has an anti-EC effect by inhibiting aerobic glycolysis and has the potential to be a drug that prevents EC in areas with a high risk of EC.

Sex differences in esophageal cancer overall and by histological subtype

Esophageal cancer is the seventh most common type of cancer in the world, the sixth leading cause of cancer-related death and its incidence is expected to rise 140% in the world in a period of 10 years until 2025. The overall incidence is higher in males, while data about prognosis and survival are not well established yet. The goal of this study was to carry out a comprehensive analysis of differences between sexes and other covariates in patients diagnosed with primary esophageal cancer. Data from 2005 to 2020 were obtained from the University Hospitals (UH) Seidman Cancer Center and from 2005 to 2018 from SEER. Patients were categorized according to histological subtype and divided according to sex. Pearson Chi-square test was used to compare variables of interest by sex and the influence of sex on survival was assessed by Kaplan Meier, log rank tests and Cox proportional hazards regression models. A total of 1205 patients were used for analysis. Sex differences in all types were found for age at diagnosis, histology, smoking status and prescriptions of NSAIDs and in SCC for age at diagnosis and alcoholism. Survival analysis didn’t showed differences between males and females on univariable and multivariable models. Males have a higher incidence of Esophageal Cancer and its two main subtypes but none of the comprehensive set of variables analyzed showed to be strongly or unique correlated with this sex difference in incidence nor are they associated with a sex difference in survival.

The dysregulation of unsaturated fatty acid-based metabolomics in the MNNG-induced malignant transformation of Het-1A cells.

Studies have shown that environmental carcinogens exerted an important function in the high incidence of esophageal cancer (EC). Nitrosamines have been identified as important environmental carcinogens for EC. This study aimed to investigate the metabolic disturbances and new key toxicological markers in the malignant transformation process of normal esophageal epithelial cells (Het-1A) induced by MNNG (N-methyl-N'-nitro-N-nitrosoguanidine). Untargeted metabolomic and lipidomic profiling analysis by using ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS) were applied to explore the metabolic network alterations of Het-1A cells. The metabolomic results showed that significant alterations were observed in metabolic signatures between different generations (P5, P15, P25, P35) and the control cell group (P0). A total of 48 differential endogenous metabolites were screened and identified, mainly containing fatty acids, amino acids, and nucleotides. The differential metabolites were predominantly linked to the pathway of biosynthesis of unsaturated fatty acids metabolism. The cell lipidomic profiling revealed that the most differential lipids contained fatty acids (FAs), phosphatidylcholines (PC), phosphatidylethanolamines (PE), and phosphatidylserines (PS). The enrichment of the lipidomic pathway also confirmed that the lipid metabolism of biosynthesis of unsaturated fatty acids was the significant variation during the cell malignant transformation. Furthermore, we detected the expression of the upstream regulatory enzymes related to the unsaturated fatty acids to explore the regulation mechanism. The expression of stearoyl-CoA desaturase (SCD), ELOVL fatty acid elongase 1 (ELOVL1) promoted, and fatty acid desaturase 1 (FADS1) inhibited the key fatty acids of unsaturated fatty acids metabolism compared to the control cell group. Overall, our results revealed that lipid fatty acid metabolism was involved in the malignant transformation of Het-1A cells induced by MNNG and deepened the awareness of the carcinogenic mechanism of environmental exposure pollutants.

The upregulated expression of RFC4 and GMPS mediated by DNA copy number alteration is associated with the early diagnosis and immune escape of ESCC based on a bioinformatic analysis.

Esophageal squamous cell carcinoma (ESCC) is a malignant tumor that commonly occurs worldwide. Usually, Asia, especially China, has a high incidence of esophageal cancer. ESCC often has a poor outcome because of a late diagnosis and lack of effective treatments.To build foundations for the early diagnosis and treatment of ESCC, we used the gene expression datasets GSE20347 and GSE17351 from the GEO database and a private dataset to uncover differentially expressed genes (DEGs) and key genes in ESCC. Notably, we found that replication factor C subunit 4 (RFC4) and guanine monophosphate synthase (GMPS) were upregulated but have been rarely studied in ESCC. In particular, to the best of our knowledge, our study is the first to explore GMPS and ESCC. Furthermore, we found that high levels of RFC4 and GMPS expression may result from an increase in DNA copy number alterations. Furthermore, RFC4 and GMPS were both upregulated in the early stage and early nodal metastases of esophageal carcinoma. The expression of RFC4 was strongly correlated with GMPS. In addition, we explored the relationship between RFC4 and GMPS expression and tumor-infiltrating immune cells (TILs) in esophageal carcinoma. The results showed that the levels of RFC4 and GMPS increased with a decrease in some tumor-infiltrating cells. Upregulated RFC4 and GMPS with high TILs indicate a worse prognosis.In summary, our study shows that RFC4 and GMPS have potential as biomarkers for the early diagnosis of ESCC and may played a crucial role in the process of tumor immunity in ESCC.