Esophageal Cancer In China Research Articles

The association between N-nitrosamines exposure and lipid metabolism in the high incidence area of esophageal cancer: A case-control analysis

Environmental carcinogens such as N-nitrosamines are high-risk factors for the development of esophageal cancer (EC). However, the association between nitrosamines exposure and lipid metabolism disorders in human EC remained largely obscure. Therefore, we conducted a population-based case-control study established with esophageal inflammation (BCH), esophageal heterotrophic hyperplasia (DYS), patients with primary EC and matched controls in high prevalence area of EC in China. Our prospective work investigated the joint and independent effects of N-nitrosamines co-exposure on the risk of EC development. Lipidomics analysis was employed to screen differential lipid biomarkers in serum, and the mediating effects of key lipid metabolites in the association between nitrosamines exposure and EC were evaluated. After adjustment for confounders, N-nitrosodimethylamine (NDMA, 1.79 (95% CI: 1.35, 2.39)), N-nitrosodi-n-propylamine (NDPA, 1.55 (95%CI: 1.15, 2.09)), N-nitrosodiethylamine (NDEA, 1.82 (95%CI: 1.36, 2.45)), N-nitrosodibutylamine (NDBA, 1.60 (95%CI: 1.20, 2.13)), N-nitrosomethylethylamine (NMEA, 1.81 (95%CI: 1.36, 2.41)) and N-nitrosomorpholine (NMOR, 1.84 (95%CI: 1.38, 2.45)) exposure all elevated the risks of EC development. The Bayesian kernel machine regression (BKMR) with hierarchical variable selection showed significant positive joint associations of urinary NDMA, NDPA, NMOR, NDEA and EC development, when all nitrosamines were at the 55th percentiles or above, compared with the median. Lipidomic screening of serum samples from the stages of BCH, DYS and EC suggested the perturbation in the biosynthesis of unsaturated fatty acid metabolism pathway, of which myristic acid (FFA 14:0), palmitoleic acid (FFA 16:1), docosahexaenoic acid (FFA 22:6) exerted remarkable mediation effects in the association between N-nitrosamines exposure and EC development. These findings provided new sights for screening early lipid biomarkers and intervention targets in human EC.

Association between surgery treatment delays and survival outcomes in patients with esophageal cancer in Hebei, China.

The delays in cancer therapies have the potential to impact disease progression by allowing the unchecked growth and spread of cancer cells. However, the understanding of the association between treatment waiting time and survival outcomes in patients with esophageal cancer (EC) is limited. This study aims to assess the impact of waiting time on survival outcomes among EC patients in Hebei province, which is recognized as one of the high-risk areas for EC in China. A total of 9,977 non-metastatic EC patients who underwent surgical treatment were identified between 2000 and 2020. The survival outcomes of overall survival (OS) and cancer-specific survival (CSS) were determined using the Kaplan-Meier methodology. Univariate and multivariate Cox regression analysis was employed to evaluate the impact of treatment delays on OS and CSS. The average delay time for initiating EC surgical treatment after diagnosis was 1.31 months (95%CI=1.29-1.34). Patients with a long delay (≥ 3 months) intreatment, comprising 9977 EC patients, exhibited significantly lower rates of 3-, 5-, and 10-year OS and CSS compared to those without any delay in treatment initiation. A long delay in EC treatment independently associated with an elevated risk of all-cause and cancer-cause mortality among various patient subgroups, including males, older individuals, single individuals, low-income patients, residents of nonmetropolitan counties, as well as those diagnosed with poorly differentiated and stage IV EC. The long delay of treatment initiation impacts the outcomes of OS and CSS in EC patients. Optimizing treatment timing may enhance life expectancy for individuals diagnosed with EC.

Changes in the recent three decades and survey on the current status of surgical treatment for esophageal cancer in China.

To review the changes and survey on status quo of the surgical treatment for esophageal cancer in China. The differences in diagnosis and treatment for esophageal cancer among hospitals in different regions across China were also investigated. We sent questionnaires to 46 hospitals across China, investigating the volume of esophageal cancer surgeries, surgical procedures, and perioperative management under the guidance of esophageal surgery chiefs. A total of 46 questionnaires were sent out and collected. The survey results showed that in the past 5 years, the volume of surgeries for esophageal cancer remained stable by 23.9% of those hospitals, increased by 30.4%, and decreased by 45.7%. Of those patients treated by surgery, 19.1% were in the early stages, and 80.9% were in locally advanced stages. In terms of surgical procedures, 73.4% of the patients were treated by minimally invasive surgery and 85.7% of esophageal substitutes were a gastric conduit, 93.1% of the substitutes were pulled to the neck through the esophageal bed. For the lymph node dissection, 78.5% of the patients had a complete two-field lymph node dissection including the para-recurrent laryngeal nerve lymph nodes. Of the patients with neoadjuvant therapy, 53.5% received chemotherapy or chemotherapy plus immunotherapy (47.0%), and 43.5% had chemoradiation. Currently, in China, minimally invasive surgery-oriented multimodality treatment, including complete two-field lymph node dissection, has become the standard approach for esophageal cancer management. Over the past decade, this standardized approach has significantly improved prognosis compared to previous decades.

Spatial and temporal distribution characteristics research of esophageal cancer in China

Objectives: To explore the spatial distribution characteristics, trend changes, and spatial clustering of esophageal cancer among residents in China at the county (city, district) scale, a spatial epidemiological approach was used, with the aim of providing localized evidence for the prevention and treatment of esophageal cancer in China. Methods: The data source was the incidence (crude rate) and mortality (crude rate) of esophageal cancer from 2005 to 2016 in the 2008-2019 edition of China Cancer Registration Annual Report published by the National Cancer Center. The Joinpoint model was used for time trend analysis. The tumor registration area in 2016 was selected as the study area for spatial feature analysis, with a total of 487 counties (cities and districts), covering 27.6% of the national population. Spatial autocorrelation analysis was performed to reveal spatial distribution characteristics by using Arcgis 10.6 software, and spatial scanning statistics was used to analyze spatial clustering characteristics by using SaTScan 9.5 software. The log-likelihood ratio (LLR) and relative risk (RR) were calculated in different windows, and the region with the largest LLR value represented the most likely cluster. Results: From 2005 to 2016, the incidence and mortality rate of esophageal cancer in China showed a trend of increasing at first and then decreasing. The incidence and mortality rate of esophageal cancer in 2016 were characterized by spatial positive correlation. High incidence and high mortality were mainly concentrated in the areas through which the Huaihe River flowed. The primary clusters (taking high incidence rate as an example LLR=6 374.41, RR=2.37, P＜0.001) were mainly distributed in Jiangsu, Anhui and Shandong in eastern China and eastern Henan and southern Hebei in central China, and secondary clusters (taking high incidence rate as an example LLR=1 971.19, RR=1.91, P＜0.001) in Gansu, Ningxia Hui Autonomous Region, Shaanxi, Sichuan and other central and western regions. Conclusions: The incidence and mortality of esophageal cancer in China have decreased since 2010. The disease burden of esophageal cancer has obvious spatial differences, and measures should be taken according to local conditions in high-risk cluster areas such as the Huaihe River basin.

The Current Status and Prospects of Early Diagnosis and Treatment of Esophageal Cancer in China

The Current Status and Prospects of Early Diagnosis and Treatment of Esophageal Cancer in China

Chinese expert consensus on surgical continuous quality improvement goals in esophageal cancer and esophagogastric junction cancer (2024 edition)

Improving the quality and efficiency of surgical diagnosis and treatment guarantees the outcome for most patients with esophageal cancer and esophagogastric junction cancer, and the continuous quality improvement mechanism oriented to the "textbook outcome" is the best choice. To ensure the successful implementation of the "Quality Control Indicators for Standardized Diagnosis and Treatment of Esophageal Cancer in China (2022 Version)" aligning with it more effectively is crucial. The Expert Committee on Quality Control of Esophageal Cancer at the National Cancer Center leads work teams comprised of multidisciplinary experts, particularly those in thoracic surgery, to establish a consensus. The current consensus comprises eight "textbook outcomes" to standardize, promote, and consolidate surgical quality management and continuously improve the surgical quality of esophageal cancer and esophagogastric junction cancer.

Analysis of the incidence and mortality trends of esophageal cancer in cancer registry areas of China and Japan.

This study aims to analyze the prevalence trend of esophageal cancer in Japan and China to provide suggestions for the prevention and treatment of esophageal cancer. The results showed that the incidence rate for the years 2010-2018 significantly decreased with an APC of 5.66%, and the mortality rate from 2010 to 2015 had an APC of -5.87% in China. However, the incidence rate of Japanese women showed an upward trend, with an APC of 4.09% from 2010 to 2019. The mortality rate of esophageal cancer in Japan showed a downward trend, with an APC of -2.96% from 2010 to 2021. From 2010 to 2018, Chinese esophageal squamous cell carcinoma accounted for the highest proportion, accounting for 85.96%, with the largest distribution in the middle, accounting for 47.25%. Patients are mostly diagnosed at stage III, and the relative survival rate from 2012 to 2015 was 30.3%. Japan also has the highest proportion of squamous cell carcinoma, and the lesions are also mostly located in the middle segment. While Japanese esophageal cancer patients are mostly diagnosed at stage I, and the relative survival rate was 41.5% in Japan from 2009 to 2011. The results of this article indicate that the current prevalence of esophageal cancer in China and Japan is generally declining, and the quality of life of patients is gradually improving, but effective screening and prevention strategies are still needed to reduce the burden of this disease.

Genetic history of esophageal cancer group in southwestern China revealed by Y‐chromosome STRs and genomic evolutionary connection analysis

Genetic and environmental factors play crucial roles in the development of esophageal cancer (EC) and contribute uniquely or cooperatively to human cancer susceptibility. Sichuan is located in the interior of southwestern China, and the northern part of Sichuan is one of the regions with a high occurrence of EC. However, the factors influencing the high incidence rate of EC in the Sichuan Han Chinese population and its corresponding genetic background and origins are still poorly understood. Here, we utilized genome-wide single nucleotide polymorphisms (SNPs) and Y-chromosome short tandem repeats (Y-STRs) to characterize the genetic structure, connection, and origin of cancer groups and general populations. We generated Y-STR-based haplotype data from 214 Sichuan individuals, including the Han Chinese EC population and a control group of Han Chinese individuals. Our results, obtained from Y-STR-based population statistical methods (analysis of molecular variance (AMOVA), principal component analysis (PCA), and phylogenetic analysis), demonstrated that there was a genetic substructure difference between the EC population in the high-incidence area of northern Sichuan Province and the control population. Additionally, there was a strong genetic relationship between the EC population in the northern Sichuan high-incidence area and those at high risk in both the Fujian and Chaoshan areas. In addition, we obtained high-density SNP data from saliva samples of 60 healthy Han Chinese individuals from three high-prevalence areas of EC in China: Sichuan Nanchong, Fujian Quanzhou, and Henan Xinxiang. As inferred from the allele frequency of SNPs and sharing patterns of haplotype segments, the evolutionary history and admixture events suggested that the Han population from Nanchong in northern Sichuan Province shared a close genetic relationship with the Han populations from Xinxiang in Henan Province and Quanzhou in Fujian Province, both of which are regions with a high prevalence of EC. Our study illuminated the genetic profile and connection of the Northern Sichuan Han population and enriched the genomic resources and features of the Han Chinese populations in China, especially for the Y-STR genetic data of the Han Chinese EC population. Populations living in different regions with high incidences of EC may share similar genetic backgrounds, which offers new insights for further exploring the genetic mechanisms underlying EC.

Survival benefits of adjuvant chemotherapy for patients with residual pathologic disease after neoadjuvant chemotherapy and surgery for locally advanced esophageal squamous cell carcinoma

Background and purposeAlthough preoperative neoadjuvant chemotherapy (NACT) or chemoradiation is the current standard of care for esophageal cancer in China, the impact of subsequent adjuvant therapy on patient prognosis remains unknown. This study aims to analyze the effect of adjuvant chemotherapy (ACT) on the survival rates of patients who have achieved a non-pathological complete response (non-pCR) after NACT and subsequent surgery. MethodsWe reviewed the data of 2193 patients with locally advanced thoracic esophageal squamous cell carcinoma (ESCC) who underwent radical surgery between January 2006 and January 2016. Of these patients, 46 received NACT and ACT, while 109 received NACT only. Propensity score matching was used to compare 86 patients, with 43 patients in the NACT+ACT group and 43 patients in the NACT group.Univariate analysis was performed using the Kaplan-Meier method and Log-rank test, while Cox regression analysis was used for multivariate analysis. ResultsMultivariate analysis revealed that pathological lymph node status (positive vs. negative) (P<0.001) and treatment modalities (NACT+ACT vs. NACT) (P=0.005) were independent prognostic factors. There was a significant difference in long-term survival rates between the NACT+ACT and NACT groups, with 5-year survival rates of 55.8% vs. 39.5%, respectively (c2=4.270, P=0.039). In patients with ypN+ status, the 5-year survival rate was 31.8% for those who received ACT after NACT and surgery, compared to 10.0% for those who did not receive additional ACT (c2=6.101, P=0.014). The corresponding percentages in patients with ypN- were 81.0% and 65.2%, respectively (c2=1.993, P=0.158). ConclusionAdjuvant chemotherapy should be recommended for locally advanced ESCC patients with residual cancer after NACT and surgery, especially for patients with nodal metastases after NACT.

Effectiveness of Endoscopic Screening on Esophageal Cancer Incidence and Mortality: A 9-Year Report of the Endoscopic Screening for Esophageal Cancer in China (ESECC) Randomized Trial.

To evaluate the effectiveness of endoscopic screening against incidence of and mortality from esophageal squamous cell carcinoma (ESCC). From January 2012 to September 2016, we conducted a community-based cluster randomized controlled trial involving permanent residents age 45-69 years in a high-risk region for ESCC in northern China. A total of 668 targeted villages were randomly assigned in a 1:1 ratio to the screening group (offered Lugol's chromoendoscopy) or control group (no screening). Intention-to-treat and per-protocol analyses were performed to compare esophageal cancer (EC) incidence and mortality between the two groups. The per-protocol analysis adjusted for nonadherence to the screening procedure. A total of 33,847 participants were included in the analysis: 17,104 in the screening group, 15,165 (88.7%) of whom underwent screening, and 16,743 in the control group. During a maximum follow-up of 9 years, EC incidence in the screening and control groups were 60.9 and 72.5 per 100,000 person-years, respectively; mortality in the screening and control groups were 29.7 and 32.4 per 100,000 person-years, respectively. Compared with the control group, the incidence and mortality of the screening group reduced by 19% (adjusted hazard ratio [aHR], 0.81 [95% CI, 0.60 to 1.09]) and 18% (aHR, 0.82 [95% CI, 0.53 to 1.26]), respectively, in the intention-to-treat analysis; and by 22% (aHR, 0.78 [95% CI, 0.56 to 1.10]) and 21% (aHR, 0.79 [95% CI, 0.49 to 1.30]), respectively, in the per-protocol analysis. With a 9-year follow-up, our trial suggests that chromoendoscopic screening induces modest reductions in EC incidence and mortality. A more efficient strategy for EC screening and subsequent patient management should be established to guarantee the effectiveness of endoscopic screening.

Disease burden and related risk factors of esophageal cancer in China and globally from 1990 to 2021, with forecast to 2035: An analysis and comparison.

In this study we estimate the burden of esophageal cancer (EC) in China and globally from 1990 to 2021, with a forecast to 2035, using Global Burden of Disease (GBD) data. We also analyze the related risk factors to investigate burden trends. Mortality, disability-adjusted life years (DALYs), crude rates, and age-standardized rates of EC were analyzed in China and globally from 1990 to 2035, utilizing GBD open data as a secondary dataset analysis of GBD data. Temporal change trends of EC risk factors were analyzed from 1990 to 2021. Joinpoint regression determined average annual percentage change (AAPC) of age-standardized rates. Descriptive analysis compared mortality and DALYs by age groups. Bayesian age-period-cohort (BAPC) predicted age-standardized mortality and DALYs rates for the next 14 years. The ASMR and ASDR fluctuations in EC were significant in China, showing an overall downward trend. Globally, although there was also a downward trend, the fluctuations were relatively mild. The number of deaths and DALYs related to EC in China and globally showed a significant upward trend. Age-specific burden trends in China for EC indicated that the age group with the peak number of EC deaths shifted to the 70-74 years age group in 2021, while DALYs peaked in the 65-69 years age group. The crude mortality rate (CMR) peaked consistently in 1990 and 2021, both within the 90-94 years age range, while the crude DALY rate (CDR) shifted to the 85-89 years age group. Overall, the burden of EC deaths and DALYs in the population aged <40 years was relatively low, increasing rapidly after the age of 40 years, reaching a peak and gradually declining, and reaching a lower level after the age of 85 years. The predictive results of the BAPC model indicated that over the next 14 years, both ASMR and ASDR for EC in China and globally would show a slight overall increase. The GBD 2021 study identified smoking, high alcohol use, chewing tobacco, and diet low in vegetables as the main risk factors affecting EC mortality rate and DALYs. Among these, smoking and alcohol use were the most significant risk factors, with a higher impact on EC in China compared to the global level. From 1990 to 2021, the overall changes in ASMR and ASDR indicate a decreasing trend in the impact of these four risk factors on EC mortality rate and DALYs. The burden of EC is expected to steadily increase in China and globally until 2035, posing a significant challenge. Targeted prevention and control policies, such as calling on people to quit smoking and reduce alcohol use, may help curb this upward trend.

Detection of Esophageal Cancer Lesions Based on CBAM Faster R-CNN

Esophageal cancer is a common malignant tumor in daily life, which seriously affects human health. Esophageal cancer in China. The incidence rate is among the highest in the world, and there are a large number of new cases of esophageal cancer every year. At present, the diagnosis of esophageal cancer is mainly based on the use of electronic gastroscopy, which reflects the observed situation on the fluorescent screen and conducts detection through the fluorescent screen. With the increasing number of patients, the pressure and intensity of the doctor's work are getting greater and greater[1]. From the perspective of molecular level, the occurrence and development of esophageal cancer, like other cancers, are related to the activation of proto-oncogenes and the inhibition of anti-apoptosis genes. CBAM Faster R-CNN is proposed to solve the problems such as the esophageal region is not obvious and the background region occupies a large proportion in the feature map obtained by the backbone network of Faster R-CNN in barium meal imaging. CBAM is added to the convolutional attention module CBAM on the basis of the original Faster R-CNN model. To enhance the saliency of the features of the esophageal region in the feature map. CBAM Faster R-CNN model was used to train the training set after data enhancement, and Recall, Precision and AP values were used for evaluation and analysis.

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.

Development of a nutritional screening and assessment indicator system for patients with esophageal cancer in China: Findings from the Delphi method.

In China, individuals diagnosed with esophageal cancer are confronted with an elevated risk of nutritional inadequacy or malnutrition throughout the course of their disease, a condition that contributes to various adverse clinical outcomes. A vast corpus of data are burgeoning at an unprecedented rate, primarily due to the revolutionary growth of digitalization technologies and artificial intelligence, notably within the domains of health care and medicine. The purpose of this investigation is to initiate the development of a nutritional screening and assessment indicator framework for patients with esophageal cancer within the Chinese context. We seek to furnish an instrumental reference to facilitate preparations for the forthcoming era of advanced, "deep," evidence-based medicine. An integrative methodology was employed to forge the preliminary draft of the nutritional screening and assessment indicator system for preoperative patients with esophageal cancer. This encompassed a rigorous literature survey, in-depth clinical practice investigation, and the facilitation of expert panel discussions. Thereafter, two iterative consultation phases were conducted using the Delphi method in China. The analytic hierarchy process was deployed to ascertain the weighting of each index within the definitive evaluation indicator system. The effective response rates for the dual rounds of expert consultation were 91.7% and 86.4%, with commensurate authority coefficients of 0.97 and 0.91. The Kendall harmony coefficients were ascertained to be 0.19 and 0.14 (p < 0.01), respectively. The culminating nutritional screening and assessment indicator system for patients with esophageal cancer comprised 5 primary-level indicators and 38 secondary-level indicators. The nutritional screening and assessment indicator system contrived for patients with esophageal cancer is underpinned by cogent theoretical principles, leverages an astute research methodology, and manifests dependable outcomes. This system may be appositely utilized as a meaningful reference for the nutritional screening and assessment process in patients afflicted with esophageal cancer.

Mortality burden and future projections of major risk factors for esophageal cancer in China from 1990 to 2019.

This study, based on Global Burden of Disease (GBD) data, aimed to report the long-term trend in mortality rates caused by risk factors for esophageal cancer (EC) in China from 1990 to 2019 and predict the burden of EC mortality caused by these risk factors over the next 15years. We examined six risk factors that influenced EC mortality rates in China and their respective rankings. Furthermore, we analyzed the number of deaths and crude mortality rates (CMR) caused by these risk factors for both sexes and different age groups. Age-standardized mortality rates (ASMR) and the number of deaths across all age groups were also analyzed. Finally, we utilized the Bayesian Age-Period-Cohort (BAPC) model to predict the trends in ASMR burden caused by these risk factors in the future. From 1990 to 2019, the percentage changes in ASMR for EC caused by the six risk factors in China were as follows: smoking (-33.4%), alcohol consumption (-23.0%), low fruit intake (-73.6%), low vegetable intake (-96.0%), high Body Mass Index (BMI) (25.1%), and tobacco chewing (-32.8%). In 2019, the top three risk factors contributing to EC ASMR in China were smoking, alcohol consumption, and high BMI. Overall, the ASMR for EC in China fluctuated and declined from 1990 to 2019. The most common risk factors for males were smoking and alcohol consumption, while low fruit intake and high BMI were the most common risk factors for females. The impact of these risk factors on EC mortality increased with age, except for the elderly population. BAPC analysis indicated that the influence of these risk factors on ASMR was expected to remain relatively stable in the next 15years, suggesting a continued significant burden of EC. The projected burden of EC mortality in China was expected to continue increasing steadily over the next 15years, highlighting the pressing need for disease control measures. To alleviate this burden, targeted prevention and control policies addressing risk factors for EC such as smoking, alcohol consumption, and high BMI are necessary.

PLK1 regulating chemoradiotherapy sensitivity of esophageal squamous cell carcinoma through pentose phosphate pathway/ferroptosis

BackgroundEsophageal squamous cell carcinoma (ESCC) is the most common pathological type of esophageal cancer in China, accounting for more than 90 %. Most patients were diagnosed with advanced-stage ESCC, for whom new adjuvant therapy is recommended. Therefore, it is urgent to explore new therapeutic targets for ESCC. Ferroptosis, a newly discovered iron-dependent programmed cell death, has been shown to play an important role in carcinogenesis by many studies. This study explored the effect of Polo like kinase 1 (PLK1) on chemoradiotherapy sensitivity of ESCC through ferroptosis MethodsIn this study, we knocked out the expression of PLK1 (PLK1-KO) in ESCC cell lines (KYSE150 and ECA109) with CRISPR/CAS9. The effects of PLK1-knock out on G6PD, the rate-limiting enzyme of pentose phosphate pathway (PPP), and downstream NADPH and GSH were explored. The lipid peroxidation was observed by flow cytometry, and the changes in mitochondria were observed by transmission electron microscopy. Next, through the CCK-8 assay and clone formation assay, the sensitivity to cobalt 60 rays, paclitaxel, and cisplatin were assessed after PLK1-knock out, and the nude mouse tumorigenesis experiment further verified it. The regulation of transcription factor YY1 on PLK1 was evaluated by dual luciferase reporter assay. The expression and correlation of PLK1 and YY1, and their impact on prognosis were analyzed in more than 300 ESCC cases from the GEO database and our center. Finally, the above results were further proved by single-cell sequencing. ResultsAfter PLK1 knockout, the expression of G6PD dimer and the level of NADPH and GSH in KYSE150 and ECA109 cells significantly decreased. Accordingly, lipid peroxidation increased, mitochondria became smaller, membrane density increased, and ferroptosis was more likely to occur. However, with the stimulation of exogenous GSH (10 mM), there was no significant difference in lipid peroxidation and ferroptosis between the PLK1-KO group and the control group. After ionizing radiation, the PLK1-KO group had higher lipid peroxidation ratio, more cell death, and was more sensitive to radiation, while exogenous GSH (10 mM) could eliminate this difference. Similar results could also be observed when receiving paclitaxel combined with cisplatin and chemoradiotherapy. The expression of PLK1, G6PD dimer, and the level of NADPH and GSH in KYSE150, ECA109, and 293 T cells stably transfected with YY1-shRNAs significantly decreased, and the cells were more sensitive to radiotherapy and chemotherapy. ESCC patients from the GEO database and our center, YY1 and PLK1 expression were significantly positively-correlated, and the survival of patients with high expression of PLK1 was significantly shorter. Further analysis of single-cell sequencing specimens of ESCC in our center confirmed the above results. ConclusionIn ESCC, down-regulation of PLK1 can inhibit PPP, and reduce the level of NADPH and GSH, thereby promoting ferroptosis and improving their sensitivity to radiotherapy and chemotherapy. Transcription factor YY1 has a positive regulatory effect on PLK1, and their expressions were positively correlated. PLK1 may be a target for predicting and enhancing the chemoradiotherapy sensitivity of ESCC.

Hsa_circ_0046534 accelerates esophageal squamous cell carcinoma proliferation and metastasis via regulating MMP2 expression by sponging miR-339-5p

Esophageal cancer is one of the most malignant gastrointestinal malignancies. Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer in China. In recent years, with developments in basic medicine, it has been demonstrated that the abnormal expression of circular RNA (circRNA) plays an important role in the progression and prognosis of ESCC. This study explored the role and downstream molecular mechanisms of circ_0046534 in ESCC. We identified circ_0046534, which was found to be highly expressed in ESCC tissues and cells. Moreover, the downregulation of circ_0046534 inhibited the proliferation, migration and invasion of ESCC cells and the growth and metastasis of ESCC tumours in vivo. Dual-luciferase reporter assays showed that circ_0046534 sponged miR-339-5p and inhibited the expression of miR-339-5p. Furthermore, MMP2 was identified to be a direct target of miR-339-5p through bioinformatics analysis. In addition, the knockdown of circ_0046534 inhibited the expression of the downstream target gene matrix metalloproteinase 2 (MMP2) by releasing the adsorption of miR-339-5p. Taken together, this study demonstrated that silencing circ_0046534 inhibited the growth and metastasis of ESCC through the miR-339-5p/MMP2 pathway. Circ_0046534 is expected to serve as a new biomarker and target for ESCC and provide a new direction for its diagnosis and treatment.

Chinese Guidelines on Perioperative Management of Resectable Esophageal Cancer (2023 edition)

The standardization of surgical treatment has become indispensable in the overall outcome of esophageal cancer care in China, but there is a notable deficiency of clinical guidelines regarding esophageal surgery. The Chinese National Cancer Center organized esophageal surgery experts from the Chinese Association of Thoracic Surgeons (CATS), Chinese Society for Thoracic and Cardiovascular Surgery (CSTCVS), and Chinese Society for Disease of the Esophagus (CSDE) to develop and establish the Chinese Guidelines on Perioperative Management of Resectable Esophageal Cancer (2023 edition). This guideline comprehensively covers all aspects of surgical treatment for esophageal cancer, including conceptual clarification, preoperative diagnosis, clinical staging, indications for surgery, multidisciplinary comprehensive treatment, surgical treatment modalities, and perioperative management. A total of 39 critical clinical questions are categorized into six domains above. This guideline follows the globally accepted approach for developing recommendations and takes into account the most recent research evidence as well as China's unique national circumstances. Its main aim is to serve as a comprehensive resource for standardizing the diagnosis and surgical treatment of esophageal cancer in China, with the ultimate goal of substantially improving the overall outcomes.

Absence of Lugol staining indicates initiation of esophageal squamous cell carcinoma: A combined genomic and epidemiologic study

The genomic characteristics during the carcinogenic process of esophageal squamous cell carcinoma (ESCC) remain largely unknown. We report here the genomic characteristics of 106 esophageal tissues of various stages from a population-based screening cohort in China ("Endoscopic Screening for Esophageal Cancer in China" trial) and 57 ESCC tissues from a local hospital. A significant increase in somatic mutation and copy number alterations is observed in the non-dysplastic Lugol unstaining lesions (ND-LULs). Extensive clonal expansion has emerged in the ND-LULs to an extent similar to that in higher-stage lesions. The burden of genomic alterations correlates with the size of LULs in the ND-LULs. 8-year follow-up shows that ND-LULs harbor an increased risk of progression to ESCC (adjusted IRR6-10mm vs. none= 4.66, adjusted IRR>10mm vs. none= 40.70), and the risk is correlated with LUL size for both non-dysplastic and dysplastic lesions. Lugol unstaining can be the initial stage in the carcinogenic process of ESCC.

Timely assessment of 5-year relative survival of esophageal cancer patients in Taizhou, Zhejiang province.

Timely assessment of 5-year relative survival of esophageal cancer patients in Taizhou, Zhejiang province.