Esophageal cancer is a major global health issue with a high mortality rate. Early diagnosis is crucial for improving patient outcomes, but traditional diagnostic methods are often invasive and costly. This study explores the potential of exhaled volatile organic compounds (VOCs) as a non-invasive diagnostic tool for esophageal cancer. Using gas chromatography-mass spectrometry (GC-MS), we analyzed the breath samples of 80 esophageal cancer patients and 60 healthy controls, identifying and quantifying over 100 VOCs. The results revealed significant differences in the concentrations of VOCs such as acetone, ethanol, and isoprene between the two groups. A multi-parameter regression diagnostic model based on a neural network algorithm achieved an accuracy of 90.3% in distinguishing esophageal cancer patients from healthy individuals. Further optimization incorporating physiological factors, including smoking, drinking, and dietary habits, improved the model's accuracy to 92.4%, with a specificity of 93.1%, representing a significant improvement over previous studies. These results suggest that VOCs analysis in exhaled breath holds great promise as a non-invasive, cost-effective, and accurate method for early detection of esophageal cancer.

Genetic testing and sequencing technologies offer a comprehensive understanding of cancer genetics, providing rapid and cost-effective solutions. In particular, these advanced technologies play an important role in assessing the complexities of the rare cancer types affecting several systems including the bone, endocrine, digestive, vascular, and soft tissue. This review will explore how genetic testing and sequencing technologies have contributed to the identification of biomarkers across several rare cancer types in diagnostic, therapeutic, and prognostic stages, thereby advancing PM.

A comprehensive literature search was conducted across PubMed (MEDLINE), EMBASE, and Web of Science using keywords related to sequencing technologies, genetic testing, and cancer. There were no restrictions on language, methodology, age, or publication date. Both primary and secondary research involving humans or animals were considered.

In practice, fluorescence in situ hybridization, karyotype, microarrays and other genetic tests are mainly applied to identify specific genetic alterations and mutations associated with cancer progression. Sequencing technologies, such as next generation sequencing, polymerase chain reaction, whole genome or exome sequencing, enable the rapid analysis of millions of DNA fragments. These techniques assess genome structure, genetic changes, gene expression profiles, and epigenetic variations. Consequently, they help detect main intrinsic markers that are crucial for personalizing diagnosis, treatment options, and prognostic assessments, leading to better patient prognosis. This highlights why these methods are now considered as primary tools in rare cancer research. However, these methods still face multiple limitations, including false positive results, limited precision, and high costs.

Genetic testing and sequencing technologies have significantly advanced the field of rare cancer research by enabling the identification of key biomarkers for precision diagnosis, treatment, and prognosis. Despite existing limitations, their integration into clinical and research fields continues to improve the development of personalized medicine strategies for rare and complex cancer types.

Multi-omics clustering has emerged as a powerful approach for understanding complex biological systems and enabling cancer subtyping by integrating diverse omics data. Existing methods primarily focus on the integration of different types of omics data, often overlooking the value of clinical context. In this study, we propose a novel framework that incorporates clinical features extracted from large language model (LLM) to enhance multi-omics clustering. Leveraging clinical data extracted from pathology reports using a BERT-based model, our framework converts unstructured medical text into structured clinical features. These features are integrated with omics data through an autoencoder, enriching the information content of each omics layer to improve feature extraction. The extracted features are then projected into a latent subspace using singular value decomposition (SVD), followed by spectral clustering to obtain the final clustering result. We evaluate the proposed framework on six cancer datasets on three omics levels, comparing it with several state-of-the-art methods. The experimental results demonstrate that the proposed framework outperforms existing methods in multi-omics clustering for cancer subtyping. Moreover, the results highlight the efficacy of integrating clinical features derived from LLM, significantly enhancing clustering performance. This work underscores the importance of clinical context in multi-omics analysis and showcases the transformative potential of LLM in advancing precision medicine.

The exact worldwide prevalence of gastroesophageal reflux disease (GERD) remains uncertain, despite its recognition as a common condition. This conundrum arises primarily from the lack of a standardized definition for GERD. The gold standard diagnostic tests for GERD, such as pH impedance testing and endoscopy, are cumbersome and impractical for assessing community prevalence. Consequently, most epidemiological studies rely on symptom-based screening tools. GERD symptoms can be both esophageal and extraesophageal, varying widely among individuals. This variability has led to multiple symptom-based definitions of GERD, with no consensus, resulting in prevalence estimates ranging from 5% to 25% worldwide. Most systematic reviews define GERD as experiencing heartburn and/or regurgitation at least once weekly, yielding a calculated prevalence of 13.98%. In 2017, the global age-standardized prevalence of GERD was estimated at 8819 per 100000 people (95% confidence interval: 7781-9863), a figure that has remained stable from 1990 to 2017. Prevalence increases with age, leading to more years lived with disability. GERD significantly impairs quality of life and can lead to multiple complications. Additionally, it imposes a severe economic burden, with the United States alone estimated to spend around 10 billion dollars annually on diagnosis and treatment. In summary, GERD prevalence varies greatly by region and even within different areas of the same province. Determining the exact prevalence is challenging due to inconsistent diagnostic criteria. However, it is well-documented that GERD poses a significant global burden, affecting the quality of life of individuals and creating a substantial healthcare cost.

This study aimed to evaluate the clinical significance of four-dimensional dynamic ventilation CT (4DCT) for assessing resectability in borderline resectable locally advanced esophageal cancer (BR-LAEC) and confirmed the pathological validity of the 4DCT results in surgery without prior treatment.

We retrospectively reviewed 128 patients (107 men; median age, 68 [range, 43-89] years) diagnosed with BR-LAEC on initial conventional CT (i-CT). These patients were initially classified into three categories: BR1 (closer to resectable), BR2 (resectability not assessable), or BR3 (closer to unresectable). Subsequent 4DCT reclassified patients as either resectable or unresectable within 1 week of i-CT. We analyzed the diagnostic shift induced by 4DCT. Additionally, 18 patients who underwent surgery without prior treatment were evaluated using 4DCT and pathological outcomes.

4DCT reclassified patients with BR-LAEC as resectable (57.0%; 73/128) and unresectable (43.0%; 55/128). Of 53 patients initially classified as BR1, 32.1% (17/53) were reclassified as unresectable, and of 47 patients initially classified as BR3, 46.8% (22/47) were reclassified as resectable. Among 28 patients initially classified as BR2, 53.6% (15/27) were reclassified as resectable and 46.4% (13/27) as unresectable. In the surgery-only cohort of 18 patients, 9 were initially classified as BR1 and 9 as BR2, and all were reclassified as resectable. These patients were pathologically confirmed to have resectable disease.

4DCT may provide information complementary to that provided by initial conventional CT in assessing resectability among patients with BR-LAEC, and could be a useful adjunct tool for guiding clinical decisions in this patient population.

Radiotherapy is a major modality for esophageal cancer (ESCA) treatment, yet radioresistance severely hampers its therapeutic efficacy. Ubiquitin-specific peptidase 14 (USP14) is a novel deubiquitinase and can mediate cancer cells' response to irradiation, although the underlying mechanism remains unclear, including in ESCA.

To evaluate the expression of USP14 in ESCA tissues or cells, we used RNA-Seq, immunoblotting, co-immunoprecipitation (Co-IP), ubiquitination, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence assays in this investigation. Additionally, we used CCK8, cloning, and migration tests to examine the proliferation and migration of ESCA cells. We also used transplantation tumor mouse model to investigate the course of the cancer cell growth. Finally, we looked into the biological processes linked to USP14 using gene set enrichment analysis (GSEA), which was later verified.

We observed a significant upregulation of USP14 in human ESCA tissues and cell lines, especially in those with radioresistance. Moreover, USP14 knockdown significantly restrained the proliferation and inhibited the radiation tolerance of ESCC cells. Here, we identified a potential inhibitor of USP14, Degrasyn (DGS), and investigated its regulatory effects on ESCA radioresistance and progression. We found that DGS had marked antiproliferative effects in radiosensitive ESCA cell lines. Notably, a low dose of DGS significantly enhanced the sensitivity of radioresistant ESCA cells to irradiation, as shown by the significantly reduced cell proliferation, migration, and invasion. Furthermore, the combination of DGS and X-ray irradiation strongly induced DNA damage in radioresistant ESCA cell lines by increasing the phosphorylation levels of H2AX (γ-H2AX) and checkpoint kinase 1/ataxia-telangiectasia-mutated-and-Rad3-related kinase (CHK1/ATR) signaling. Animal experiments confirmed the effective role of the DGS and X-ray combined treatment in reducing tumor growth and irradiation tolerance of ESCA in vivo with undetectable toxicity. Importantly, the promotive and malignant biological behaviors of ESCA cells suppressed by the DGS/X-ray combination treatment were almost eliminated by USP14 overexpression, along with the abolished DNA damage process. Mechanistically, we found that USP14 could interact with Yes-associated protein 1 (YAP1) and induce its deubiquitination in radioresistant ESCA cells. Interestingly, we discovered that DGS/X-ray co-therapy significantly reduced the stability of YAP1 and induced its ubiquitination in radioresistant ESCA cells. More importantly, the proliferation, epithelial-mesenchymal tansition (EMT) process, and DNA damage regulated by DGS/X-ray and USP14 knockdown were significantly eliminated when YAP1 was overexpressed in radioresistant ESCA cells.

These data revealed the potential role of DGS/X-ray co-therapy in controlling ESCA resistance to radiotherapy by inhibiting the USP14/YAP1 axis, providing a candidate strategy for ESCA treatment.

Esophageal and gastric cancer were among the top 10 most common cancers worldwide. In addition, sex-specific differences were observed in the incidence. Due to their anatomic proximity, the 2 cancers have both different but also shared risk factors and epidemiological features. Exploring the potential correlated incidence pattern of them, holds significant importance in providing clues in the etiology and preventive strategies.

This study aims to explore the spatiotemporal correlation between the incidence patterns of esophageal and gastric cancer in 204 countries and territories from 2010 to 2019 so that prevention and control strategies can be more effective.

The data of esophageal and gastric cancer were sourced from the Global Burden of Disease (GBD). Spatial autocorrelation analysis using Moran I in ArcGIS 10.8 (Esri) was performed to determine spatial clustering of each cancer incidence. We classified different risk areas based on the risk ratio (RR) of the 2 cancers in various countries to the global, and the correlation between their RR was evaluated using Pearson correlation coefficient. Temporal trends were quantified by calculating the average annual percent change (AAPC), and the correlation between the temporal trends of both cancers was evaluated using Pearson correlation coefficients.

In 2019, among 204 countries and territories, the age-standardized incidence rates (ASIR) of esophageal cancer ranged from 0.91 (95% CI 0.65-1.58) to 24.53 (95% CI 18.74-32.51), and the ASIR of gastric cancer ranged from 3.28 (95% CI 2.67-3.91) to 43.70 (95% CI 34.29-55.10). Malawi was identified as the highest risk for esophageal cancer (male RR=3.27; female RR=5.19) and low risk for gastric cancer (male RR=0.21; female RR=0.23) in both sexes. Spatial autocorrelation analysis revealed significant spatial clustering of the incidence for both cancers (Moran I>0.20 and P<.001). A positive correlation between the risk of esophageal and gastric cancer was observed in males (r=0.25, P<.001). The ASIR of both cancers showed a decreasing trend globally. The ASIR for esophageal and gastric cancer showed an AAPC of -1.43 (95% CI -1.58 to -1.27) and -1.76 (95% CI -2.08 to -1.43) in males, and -1.93 (95% CI -2.11 to -1.75) and -1.79 (95% CI -2.13 to -1.46) in females. In addition, a positive correlation between the temporal trends in ASIR for both cancers was observed at the global level across sexes (male r=0.98; female r=0.98).

Our study shows that there was a significant spatial clustering of the incidence for esophageal and gastric cancer and a positive correlation between the risk of both cancers across countries was observed in males. In addition, a codescending incidence trend between both cancers was observed at the global level.

The aim of this study was to explore the high-risk factors for recurrence in patients with locally advanced esophageal squamous cell carcinoma (ESCC) undergoing definitive chemoradiotherapy or radiotherapy (dCRT or dRT). Conditional survival (CS) was used to evaluate the dynamic survival and recurrence risk of patients after treatment, and individualized monitoring strategies were developed for patients. Logistic regression analysis was performed to determine independent recurrence risk factors. Calibration curves and receiver operating characteristic (ROC) curve were used to evaluate nomogram models. Kaplan-Meier curves were used to compare survival rates in different groups and to calculate CS rate. A total of 677 patients were included. Multivariate logistic analyses demonstrated that chemotherapy cycles, tumor length, body mass index (BMI), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) were independent recurrence risk factors (p < 0.05). Subsequently, we constructed nomogram models to predict recurrence and risk stratification. Kaplan-Meier curves showed that conditional locoregional recurrence-free survival and distant metastasis-free survival of patients in different risk groups and clinical stages progressively increased with survival time, whereas local recurrence and distant metastasis annual recurrence rates decreased yearly with increasing survival time. Finally, we developed an individualized follow-up strategy based on CS at different frequencies. Individualized follow-up strategies developed on the basis of CS can better monitor the changes in patients' conditions and contribute to timely salvage treatment and rational allocation of healthcare resources.

Esophageal cancer has a poor prognosis and survival rate due to its high incidence in Asia, lack of early symptoms and limited treatment options. In recent years, many clinical trials have demonstrated that immunotherapy has greatly improved the survival of patients with esophageal cancer. In addition, the combination of neoadjuvant immunotherapy with other popular therapeutic regimens has shown good efficacy and safety. In this review, we summarize the progress of clinical trials and some breakthroughs in neoadjuvant immunotherapy for esophageal cancer in recent years and suggest the possibility of multimodal neoadjuvant immunotherapy regimens, as well as directions for future development.

Esophageal cancer is a major public health issue, yet risk factors for its occurrence are still insufficiently known. This study aimed to estimate the global burden of esophageal cancer and its risk factors.

This ecological study presented the incidence, mortality, and Disability-Adjusted Life Years (DALYs) of esophageal cancer in the world. This study collected the Global Burden of Disease study data from 1990 to 2019. Trends in esophageal cancer burden were assessed using the joinpoint regression analysis and calculating the average annual percent change (AAPC).

Globally, in 2019, in both sexes and all ages, the ASR for the incidence of esophageal cancer was 6.5 per 100,000 and for mortality, 6.1 per 100,000. The global proportion of DALYs for esophageal cancer attributable to selected behavioral, metabolic, and dietary risk factors was similar in males and females: chewing tobacco (3.8% vs. 5.1%), diet low in fruits (10.1% vs. 12.6%), diet low in vegetables (3.3% vs. 4.6%), and high body mass index (18.8% vs. 19.3%). However, the proportion of DALYs for esophageal cancer attributable to smoking and alcohol use was 4-5 times higher in males than in females (50.1% vs. 11.3%, and 29.6% vs. 5.1%, respectively). From 1990 to 2019, a significant decrease in global trends in rates of DALYs for esophageal cancer attributable to smoking (AAPC = -1.6%), chewing tobacco (AAPC = -0.5%), alcohol use (AAPC = -1.0%), a diet low in fruits (AAPC = -3.1%), and a diet low in vegetables (AAPC = -3.6%) was observed, while a significant increase in trends was observed in DALYs rates for esophageal cancer attributable to a high body mass index (AAPC = +0.4%).

More epidemiological research is needed to elucidate the relationship between esophageal cancer and certain risk factors and guide prevention efforts.

Human papillomavirus (HPV) is a prevalent sexually transmitted infection, implicated in various cancers, yet its influence in non-cancerous oesophageal tissue remains unclear. This study aims to investigate the gene expression changes associated with high-risk HPV (HR-HPV) in non-cancerous oesophageal tissue to elucidate potential early oncogenic mechanisms. Using RNA sequencing, we compared transcriptomic profiles of HPV-positive and HPV-negative non-cancerous oesophageal tissues. Differential gene expression analysis revealed significant upregulation of cell cycle and DNA replication pathways in HPV-positive samples, specifically involving key genes such as CCNA2, DSN1, and MCM10, which are known to regulate cellular proliferation and genomic stability. Additionally, kinase and transcription factor enrichment analyses highlighted HR-HPV-associated regulatory molecules, including E2F4 and CSNK2A1, suggesting HPV's role in modulating host cell cycle control. These findings support the hypothesis that HPV infection may initiate cellular alterations in oesophageal tissue, potentially predisposing it to malignancy. This study contributes to understanding HPV's impact in non-cancerous tissues and identifies possible biomarkers for early HPV-related cellular changes, offering insights into HPV-driven cancer development beyond traditionally associated sites.

Esophageal cancer (EC) is the sixth leading cause of cancer-related mortality worldwide, continuing to be a significant public health concern. The purpose of this study is to assess the impact of staging and histopathology of EC on associated mortality. The study also aims to further investigate clinical characteristics, prognostic factors, and survival outcomes in patients diagnosed with EC between 2010 and 2017. Furthermore, we analyzed the interaction between tumor histology and staging and the risk of mortality.

A total of 24,011 patients diagnosed with EC between 2010 and 2017 in the United States were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database. Demographic parameters, tumor stage, and histologic subtypes were analyzed and associated overall mortality (OM) and cancer-specific mortality (CSM) were measured across all subgroups. Covariates reaching the level of statistical significance, demonstrable by a p-value equal to or less than 0.01, were incorporated into a multivariate Cox proportional hazards model. A hazard ratio greater than 1 was indicative of an increased risk of mortality in the presence of the variable under discussion. Additionally, the study explores the interaction between histology and tumor stage on outcomes.

The majority of patients were male (80.13%) and non-Hispanic white (77.87%), with a predominant age at diagnosis of between 60 and 79 years (59.86%). Adenocarcinoma was the most common tumor subtype (68.17%), and most patients were diagnosed at a distant stage (41.29%). Multivariate analysis revealed higher mortality risks for males, older patients, unmarried individuals, and those with advanced-stage tumors. Higher income, receiving radiation or chemotherapy, and undergoing surgery were associated with lower mortality. Tumor subtype significantly influenced mortality, with squamous cell carcinoma and neuroendocrine tumors showing higher hazard ratios compared to adenocarcinoma. Adenocarcinoma is linked to a poorer prognosis at advanced stages, whereas the opposite trend is observed for SCC.

The study identifies significant demographic and clinicopathologic factors influencing mortality in esophageal cancer patients, highlighting the importance of early diagnosis and treatment intervention. Future research should focus on tailored treatment strategies to improve survival outcomes in high-risk groups and to understand the interaction between tumor histology and tumor stage.

The immune system and inflammatory processes play crucial roles in the development of esophageal cancer (EC). This study aimed to investigate the causal relationships between 731 immune cell phenotypes, 91 circulating inflammatory proteins, and EC, with a particular focus on the mediating role of circulating inflammatory proteins. Utilizing public genetic data, we applied a 2-sample Mendelian Randomization (MR) method to examine the causal relationships between 731 immune cell phenotypes, 91 circulating inflammatory proteins, and EC. Comprehensive sensitivity analyses were conducted to assess the robustness, heterogeneity, and horizontal pleiotropy of the MR results. Additionally, a 2-step MR method was employed to quantify the impact and proportion of immune cell phenotypes mediated by circulating inflammatory proteins on EC. Eleven immune cell phenotypes and 1 inflammatory cytokine were found to have causal relationships with EC, with results stable across all sensitivity analyses. Mediation analyses revealed that only 2 cell phenotypes had causal relationships with EC through interleukin-10: CD3 on human leukocyte antigen-DR (HLA-DR)+ T cells (mediation effect = -0.009; mediation proportion = 12.01%) and monocytic myeloid-derived suppressor cell absolute count (mediation effect = 0.018; mediation proportion = 18.97%). This study enhances the understanding of the causal relationships between immune cells, circulating inflammatory proteins, and EC. The findings highlight the potential mediating role of interleukin-10, providing new insights into the mechanisms by which immune cells may influence esophageal tumorigenesis.

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignant tumor of the digestive tract. Clinical findings reveal that the five-year survival rate for mid-to late-stage ESCC patients is merely around 20 %, whereas those diagnosed at an early stage can achieve up to a 95 % survival rate. Consequently, early detection is paramount to improving ESCC patient survival. Protein markers are essential for diagnosing diseases, and the identification of new candidate proteins associated with ESCC through the protein-protein interaction (PPI) network is aimed for in this paper. The PPI network related to ESCC was constructed using protein data, comprising 2094 nodes and 19,660 edges. To assess the nodes' importance in the network, three metrics-degree centrality, betweenness centrality, and closeness centrality-were employed, leading to the identification of 81 key proteins. Subsequently, the biological significance of these proteins in the network was explored, combining biomedical knowledge from three perspectives: network, node, and cluster. The results demonstrated that 52 out of 81 key proteins were confirmed to be linked to ESCC. Among the remaining 29 unreported proteins, 18 displayed significant biological significance, indicating their potential as protein markers related to ESCC.

In adults, esophageal cancers are a global health concern. Esophageal squamous cell carcinoma (ESCC) accounts for approximately 90% of esophageal carcinomas. The prognosis of esophageal cancers remains dismal, with a five-year survival rate below 20%. It typically affects older patients, and for now, ESCC after esophageal atresia has not been reported in patients younger than 18 years. We present an exceptional case of an ESCC in a 13-year-old boy with a history of esophageal atresia and corrective surgery in infancy. After the surgery the patient was lost to surgical follow up for over ten years and then presented to our emergency department with respiratory distress requiring antibiotic therapy and supplemental oxygen. Radiologic imaging revealed a volume reduction of the right lung with bronchiectasis, as well as esophageal stenosis at the level of the previous anastomosis, with an adjacent abscess in the right lung. These changes may have arisen due to a chronic fistula from the esophagus to the right lung. Initial interventional therapy with a stent implantation had no lasting success and, in an effort to prevent further aspiration into the right lung, a cervical esophagus stoma was established, and the patient received prolonged antibiotic treatment. However, a thoracic CT scan performed 4 months later revealed a large, retrospectively progressive prevertebral mass originating from the distal portion of the esophagus below the stenosis, compressing the trachea and the right main bronchus. The patient's condition rapidly worsened and he developed respiratory failure, requiring veno-venous extracorporeal membrane oxygenation. Unfortunately, an endoscopic biopsy revealed an advanced ESCC. With no rational treatment options available, we changed the goals of care to a palliative setting. The key message of this case is that in adolescents with chronic infections, an abscess can potentially mask a malignant transformation. Therefore, in adolescents, with an history of corrective surgery for esophageal atresia and chronic complications, consideration should also be given to the possibility of squamous cell carcinoma of the esophagus.

Gastrointestinal cancers account for over a quarter of all cancer cases and are associated with poor prognosis and high mortality rates. The IKK complex (the canonical I kappa B kinase), comprising the CHUK, IKBKB, and IKBKG genes, plays a crucial role in activating the NF-kB signaling pathway. This study aimed to analyze publicly available bioinformatics data to elucidate the oncogenic role of IKK genes in selected gastrointestinal cancers. Our findings reveal that IKBKB and IKBKG are significantly upregulated in all examined cancers, while CHUK is upregulated in esophageal carcinoma and stomach adenocarcinoma. Additionally, the expression of IKK genes varies with histological grade and nodal metastases. For instance, in stomach adenocarcinoma, CHUK and IKBKB are upregulated in higher histological grades and greater lymph node infiltration. Lower expression levels of CHUK, IKBKB, and IKBKG in stomach adenocarcinoma and IKBKB in esophageal squamous cell carcinoma correlate with shorter overall survival. Conversely, in esophageal adenocarcinoma, reduced IKBKG expression is linked to longer overall survival, while higher IKBKB expression in colon adenocarcinoma is associated with longer overall survival. Given the significant role of IKK genes in the development and progression of selected gastrointestinal cancers, they hold potential as prognostic markers and therapeutic targets, offering valuable insights for clinical practice.

A hyperechoic nodule in the liver has a broad differential; however, the vast majority are benign lesions. We report a case of a 29-year-old man with a history of anxiety and depression who presented to the hospital due to a 12-day history of epigastric pain with radiation to the back, fevers, and night sweats. Initial imaging revealed a small hyperechoic nodule on the liver, originally believed to be an abscess. Image-guided aspiration was attempted but no fluid could be drained. An endoscopic ultrasound was pursued to further evaluate the lesion and obtain a biopsy. An ulcerated esophageal mass was incidentally identified on endoscopy. Hepatic and esophageal biopsies demonstrated moderately differentiated adenocarcinoma, with esophageal adenocarcinoma as the primary source. This case highlights an interesting presentation for the rare occurrence of metastatic esophageal adenocarcinoma in a young, healthy individual without identifiable risk factors.

Currently, the incidence of esophageal cancer continues to rise around the world. Because of its good early prognosis, it is of great significance to establish an effective model for predicting the survival of EC patients. The purpose of this study was to predict survival after diagnosis in Esophageal Cancer (EC) patients by constructing a valid clinical nomogram. In this study, 5037 EC patient samples diagnosed from 2010 to 2015 were screened by accessing the SEER database, and 8 independent prognostic factors were screened by various methods, and Cox multivariate regression was included to construct a prognostic model and nomogram for esophageal cancer. to estimate esophageal cancer recurrence and overall survival. Calibration of the nomogram predicted probabilities of 1-year, 3-year and 5-year survival probability, which were closely related to actual survival. In conclusion, this study validated that the column-line graphical model can be considered an individualized quantitative tool for predicting the prognosis of patients with EC in order to assist clinicians in making therapeutic decisions.

Gastrointestinal cancers continue to pose a significant global health challenge, with millions of new cases diagnosed each year. Despite advancements in treatment, the prognosis for many patients remains poor. This article explores the potential of garcinol, a polyisoprenylated benzophenone found in various Garcinia species, as a therapeutic agent against gastrointestinal malignancies. The objective is to review recent research on garcinol's anticancer properties, its mechanisms of action, and safety aspects. Garcinol exhibits anticancer effects in esophageal, gastric, colorectal, pancreatic, and liver cancers by inhibiting metastasis, inducing apoptosis, and targeting key molecular pathways in cancer progression. Nanotechnology is explored as a means to enhance garcinol delivery and efficacy. Safety assessments suggest a promising toxicity profile. Garcinol shows significant potential as a natural therapeutic agent for gastrointestinal cancers, and future research is needed on optimizing its delivery, exploring synergistic combinations, and conducting clinical trials to validate its efficacy and safety for clinical applications.

Despite advancing treatment methods, esophageal cancer (EC) maintains a high mortality rate and poor prognosis. Through various mechanisms, aspirin has been suggested to have a chemopreventive effect on EC. However, the long-term impact, particularly regarding the rate of metastasis, needs to be further elucidated. NIS 2016-2020 was used to identify adult patients (age > 18 years) with EC using ICD-10 codes. Patients with missing demographics and mortality were excluded. Patients were stratified into two groups based on aspirin use. Data were collected on patient demographics, Elixhauser Comorbidity Index (ECI), and comorbidities (hypertension, chronic pulmonary disease, coronary artery disease (CAD), chronic kidney disease (CKD), congestive heart failure (CHF), coagulopathy, alcohol use, smoking, and obesity). The outcomes studied were rates of total metastasis, gastrointestinal (GI) metastasis, non-GI metastasis, and lymphoid metastasis. Multivariate logistic regression analysis was performed to evaluate the impact of aspirin use on various metastases after adjusting for patient demographics, comorbidities, and ECI. Out of 190,655 patients, 20,650 (10.8%) patients were aspirin users. Majority of the patients in the aspirin group were aged > 65 years (74.7%), males (82.1%), White race (84%), and had medicare insurance (71%). There was a higher incidence of diabetes, hypertension, chronic pulmonary disease, CAD, CKD, CHF, and smoking in aspirin users than non-aspirin users. Patients with aspirin users had a lower incidence of metastasis (28.9% vs. 38.7%, P < 0.001), GI metastasis (14.2% vs. 20.6%, P < 0.001), non-GI metastasis (15.1% vs. 22%, P < 0.001), and lymphoid metastasis (8.9% vs. 11.3%, P < 0.001) than non-aspirin users. After adjusting for confounding factors, patients with aspirin use had lower odds of having metastasis (aOR-0.73, 95% CI-0.70-0.77, P < 0.001). Our study noted that aspirin use is associated with a reduction in the rate of metastasis in patients with EC. These studies support the use of aspirin in patients with EC and suggest the need for further studies to understand the mechanism by which aspirin use reduces metastasis in patients with EC.

With one of the highest mortality rates of all malignancies, the 5-year survival rate for esophageal cancer is under 20%. Depending on the stage and extent of the disease, the current standard of care treatment paradigm includes chemotherapy or chemoradiotherapy followed by surgical esophagogastrectomy, with consideration for adjuvant immunotherapy for residual disease. This regimen has high morbidity, due to anatomic changes inherent in surgery, the acuity of surgical complications, and off-target effects of systemic chemotherapy and immunotherapy. We begin with a review of current treatments, then discuss new and emerging targets for therapies and advanced drug delivery systems. Recent and ongoing preclinical and early clinical studies are evaluating traditional tumor targets (e.g., human epidermal growth factor receptor 2), as well as promising new targets such as Yes-associated protein 1 or mammalian target of rapamycin to develop new treatments for this disease. Due the function and location of the esophagus, opportunities also exist to pair these treatments with a drug delivery strategy to increase tumor targeting, bioavailability, and intratumor concentrations, with the two most common delivery platforms being stents and nanoparticles. Finally, early results with antibody drug conjugates and chimeric antigenic receptor T cells show promise as upcoming therapies. This review discusses these innovations in therapeutics and drug delivery in the context of their successes and failures, with the goal of identifying those solutions that demonstrate the most promise to shift the paradigm in treating this deadly disease.

Long non-coding RNA (lncRNA) U731166 and microRNA (miR)-3607-3p are two ncRNAs with critical roles in cancer biology, while their involvement in esophageal squamous-cell carcinomas (ESCC) is unclear. We predicted that U731166 and miR-3607-3p might interact with each other. This study aimed to investigate their role and interaction in ESCC.

This study was therefore conducted to explore the involvement of U731166 and miR-3607-3p in ESCC, with a focus on the interaction between them.

Paired ESCC and non-tumor tissue samples were recruited from 72 ESCC patients. By RT-Qpcr, level of U731166 and miR-3607-3p in paired tissues was measured. By RNA-RNA pulldown assay, the direct interaction between U731166 and miR-3607-3p was detected. U731166 overexpression or miR-3607-3p overexpression was performed to investigate their role in regulating the expression of each other. By RT-qPCR and Western blot analysis, the role of U731166 and miR-3607-3p in regulating the level of TGFBR1 was assessed. By Transwell assays, cell invasion and migration were analyzed.

Compared to non-tumor tissues, U731166 was highly upregulated in ESCC, while miR-3607-3p was downregulated in ESCC. U731166 and miR-3607-3p directly interacted with each other, but they are not closely correlated and did not regulate the level of each other. Moreover, U731166 reversed the role of miR-3607-3p in downregulating TGFBR1 and inhibiting cancer cell invasion and migration. U731166 and miR-3607-3p were closely associated with patients' tumor metastasis but not tumor size.

U731166 may upregulate TGFBR1 by sponging miR-3607-3p in ESCC cells to promote tumor metastasis.

The nuclear receptor Nur77 plays paradoxical roles in numerous cancers. However, whether Nur77 inhibits esophageal squamous cell carcinoma (ESCC) growth and affects immunological responses against ESCC has not been determined. The functional role of Nur77 in ESCC was investigated in this study using human ESCC cell lines, quantitative real-time polymerase chain reaction (PCR), cell proliferation and colony formation assays, flow cytometry analysis, western blotting and animal models. The target gene controlled by Nur77 was verified using dual-luciferase reporter assays, chromatin immunoprecipitation analysis and functional rescue experiments. To examine the clinical importance of Nur77, 72 human primary ESCC tissues were subjected to immunohistochemistry. Taken together, these findings showed that, both in vitro and in vivo, Nur77 dramatically reduced ESCC cell growth and triggered apoptosis. Nur77 directly interacts with the interferon regulatory factor 1 (IRF1) promoter to inhibit its activity in ESCC. Pharmacological induction of Nur77 using cytosporone B (CsnB) inhibited ESCC cell proliferation and promoted apoptosis both in vitro and in vivo. Furthermore, CsnB increased CD8+ T-cell infiltration and cytotoxicity to inhibit the formation of ESCC tumors in an immunocompetent mouse model. In ESCC tissues, Nur77 expression was downregulated, and IRF1 expression was increased; moreover, their expression levels were negatively related. IRF1 and Nur77 were strongly correlated with overall survival. These findings suggested that Nur77 targets and regulates the IRF1/PD-L1 axis to serve as a tumor suppressor in ESCC. Graphical abstract of the regulatory mechanism of Nur77 overexpression downregulates IRF1 in the inhibition of ESCC progression and enhance anti-PD-1 therapy efficacy.

Esophageal cancer (EC) poses a significant challenge to the healthcare system due to its profound impact on cancer-related morbidity and mortality worldwide. This malignancy ranks among the most arduous conditions confronting the surgeon. EC arises from a complex interplay of genetic predispositions and environmental factors. While the incidence of esophageal adenocarcinoma (EAC) is on the rise in the West, esophageal squamous cell carcinoma (ESCC) remains prevalent in the East. Chronic inflammation plays a pivotal role in the initiation and progression of EC. Accordingly, serum inflammatory markers, growth factors, and cytokines have been shown to be clinically useful. Thus, evaluating serum cytokine levels for EC prediction is a safe and feasible screening method. Given the aggressive nature and poor prognosis of the disease, innovative approaches to diagnosis, prognosis, and management of EC are indispensable. This review discusses the major risk factors and the current landscape of EC, with a specific focus on the potential contributions of new inflammatory markers to enhance disease management and improve patient outcomes.

Esophageal cancer (EC) remains a significant health challenge globally, with increasing incidence and high mortality rates. Despite advances in treatment, there remains a need for improved diagnostic methods and understanding of disease progression. This study addresses the significant challenges in the automatic classification of EC, particularly in distinguishing its primary subtypes: adenocarcinoma and squamous cell carcinoma, using histopathology images. Traditional histopathological diagnosis, while being the gold standard, is subject to subjectivity and human error and imposes a substantial burden on pathologists. This study proposes a binary class classification system for detecting EC subtypes in response to these challenges. The system leverages deep learning techniques and tissue-level labels for enhanced accuracy. We utilized 59 high-resolution histopathological images from The Cancer Genome Atlas (TCGA) Esophageal Carcinoma dataset (TCGA-ESCA). These images were preprocessed, segmented into patches, and analyzed using a pre-trained ResNet101 model for feature extraction. For classification, we employed five machine learning classifiers: Support Vector Classifier (SVC), Logistic Regression (LR), Decision Tree (DT), AdaBoost (AD), Random Forest (RF), and a Feed-Forward Neural Network (FFNN). The classifiers were evaluated based on their prediction accuracy on the test dataset, yielding results of 0.88 (SVC and LR), 0.64 (DT and AD), 0.82 (RF), and 0.94 (FFNN). Notably, the FFNN classifier achieved the highest Area Under the Curve (AUC) score of 0.92, indicating its superior performance, followed closely by SVC and LR, with a score of 0.87. This suggested approach holds promising potential as a decision-support tool for pathologists, particularly in regions with limited resources and expertise. The timely and precise detection of EC subtypes through this system can substantially enhance the likelihood of successful treatment, ultimately leading to reduced mortality rates in patients with this aggressive cancer.

Gender and geographic access to care play a large role in health disparities in esophageal cancer care. The aim of our study was to evaluate disparities in peri-operative outcomes for patients undergoing esophagectomy based on gender and geographic location.

A retrospective cohort of prospectively collected data from patients who underwent esophagectomy from 2003 to 2022 was identified and analyzed based on gender and county, which were aggregated into existing state-level "metropolitan" versus "rural" designations. The demographics, pre-operative treatment, surgical complications, post-operative outcomes, and length of stay (LOS) of each group were analyzed using chi-squared, paired t-tests and single-factor ANOVA.

Of the 1545 patients, men (83.6%) and women (16.4%) experienced similar rates of post-operative complications, but women experienced significantly longer hospital (p = 0.002) and ICU (p = 0.03) LOSs as compared with their male counterparts, with no differences in 30-day mortality. When separated by geographic criteria, rural women were further outliers, with significantly longer hospital LOSs (p < 0.001) and higher rates of ICU admission (p < 0.001).

Rural female patients undergoing esophagectomy were more likely to have a longer inpatient recovery process compared with their female metropolitan or male counterparts, suggesting a need for more targeted interventions in this population.

To clarify the causal relationship between factors contributing to the postoperative survival of patients with esophageal cancer.

A cohort of 195 patients who underwent surgery for esophageal cancer between 2008 and 2021 was used in the study. All patients had preoperative chest computed tomography (CT) and positron emission tomography-CT (PET-CT) scans prior to receiving any treatment. From these images, high throughput and quantitative radiomic features, tumor features, and various body composition features were automatically extracted. Causal relationships among these image features, patient demographics, and other clinicopathological variables were analyzed and visualized using a novel score-based directed graph called "Grouped Greedy Equivalence Search" (GGES) while taking prior knowledge into consideration. After supplementing and screening the causal variables, the intervention do-calculus adjustment (IDA) scores were calculated to determine the degree of impact of each variable on survival. Based on this IDA score, a GGES prediction formula was generated. Ten-fold cross-validation was used to assess the performance of the models. The prediction results were evaluated using the R-Squared Score (R2 score).

The final causal graphical model was formed by two PET-based image variables, ten body composition variables, four pathological variables, four demographic variables, two tumor variables, and one radiological variable (Percentile 10). Intramuscular fat mass was found to have the most impact on overall survival month. Percentile 10 and overall TNM (T: tumor, N: nodes, M: metastasis) stage were identified as direct causes of overall survival (month). The GGES casual model outperformed GES in regression prediction (R2  = 0.251) (p < 0.05) and was able to avoid unreasonable causality that may contradict common sense.

The GGES causal model can provide a reliable and straightforward representation of the intricate causal relationships among the variables that impact the postoperative survival of patients with esophageal cancer.

Neoadjuvant chemoradiation and chemotherapy are recommended for the treatment of nonmetastatic esophageal cancer. The benefit of neoadjuvant treatment is mostly limited to patients who exhibit pathologic complete response (pCR). Existing estimates of pCR rates among patients receiving neoadjuvant therapy have not been synthesized and lack precision.

We conducted an independently funded systematic review and meta-analysis (PROSPERO CRD42023397402) of pCR rates among patients diagnosed with esophageal cancer treated with neoadjuvant chemo(radiation). Studies were identified from Medline, EMBASE, and CENTRAL database searches. Eligible studies included trials published from 1992 to 2022 that focused on nonmetastatic esophageal cancer, including the gastroesophageal junction. Histology-specific pooled pCR prevalence was determined using the Freeman-Tukey transformation and a random effects model.

After eligibility assessment, 84 studies with 6451 patients were included. The pooled prevalence of pCR after neoadjuvant chemotherapy in squamous cell carcinomas was 9% (95% CI: 6%-14%), ranging from 0% to 32%. The pooled prevalence of pCR after neoadjuvant chemoradiation in squamous cell carcinomas was 32% (95% CI: 26%-39%), ranging from 8% to 66%. For adenocarcinoma, the pooled prevalence of pCR was 6% (95% CI: 1%-12%) after neoadjuvant chemotherapy, and 22% (18%-26%) after neoadjuvant chemoradiation.

Under one-third of patients with esophageal cancer who receive neoadjuvant chemo(radiation) experience pCR. Patients diagnosed with squamous cell carcinomas had higher rates of pCR than those with adenocarcinomas. As pCR represents an increasingly utilized endpoint in neoadjuvant trials, these estimates of pooled pCR rates may serve as an important benchmark for future trial design.

In the United States, clinical guidelines recommend daily use of proton pump inhibitors (PPIs) amongst individuals diagnosed with Barrett's esophagus to decrease the risk of progression to dysplasia and neoplasia. Prior studies documenting adherence to PPIs in this population have not characterized heterogeneity in adherence patterns. Factors that may relate to adherence are incompletely described.

We used administrative claims data from the Merative MarketScan Commercial Claims and Encounters database to conduct a retrospective study of adherence to prescription PPIs. A cohort of individuals diagnosed with incident Barrett's esophagus between 2010 and 2019 was identified. Group-based trajectory models were generated to detect longitudinal adherence subgroups.

79 701 individuals with a new diagnosis of Barrett's esophagus were identified. The best fitting model detected five distinct adherence trajectory groups: consistently high (44% of the population), moderate decline (18%), slow decline (12%), rapid decline (10%), and decline-then-increase (16%). Compared to individuals starting PPIs, those already using PPIs were less likely to have a declining adherence pattern. Other factors associated with membership in a declining adherence group included (but were not limited to): female sex, having a past diagnosis of anxiety or depression, and having one or more emergency department visits in the past year.

Using an exploratory method, we detected heterogeneity in adherence to prescription PPIs. Less than half of individuals were classified into the consistently high adherence group, suggesting that many individuals with Barrett's esophagus receive inadequate pharmacologic therapy.

MicroRNAs (miRNAs) can function as negative regulators of gene expression by binding to the 3'-untranslated region (3'-UTR) of target genes. The aberrant expression of miRNAs in neoplasm is extensively associated with tumorigenesis and cancer progression, including esophageal squamous cell carcinoma (ESCC). Our previous investigation has identified the oncogenic roles of Peroxiredoxin2 (PRDX2) in ESCC progression; however, its upstream regulatory mechanism remains to be elucidated. By merging the prediction results from miRWalk2.0 and miRNA differential expression analysis results based on The Cancer Genome Atlas Esophageal Carcinoma (TCGA-ESCA) database, eight miRNA candidates were predicted to be the potential regulatory miRNAs of PRDX2, followed by further identification of miR-92a-2-5p as the putative miRNA of PRDX2. Subsequent functional studies demonstrated that miR-92a-2-5p can suppress ESCC cell proliferation and migration, as well as tumor growth in subcutaneous tumor xenograft models, which might be mediated by the suppression of AKT/mTOR and Wnt3a/β-catenin signaling pathways upon miR-92a-2-5p mimic transfection condition. These data revealed the tumor suppressive functions of miR-92a-2-5p in ESCC by targeting PRDX2.

N6-methyladenosine (m6A) is the most pervasive modification of RNA methylation in eukaryotic cells. m6A modification plays a pivotal role in tumorigenesis and progression in many types of cancers. Until now, the role of m6A modification in esophageal carcinoma (ESCA) has remained obscure. The aim of the study was to construct and validate prognostic signatures based on m6A regulators for ESCA.

Transcriptomic data, somatic mutations and clinical information were obtained from The Cancer Genome Atlas (TCGA). Copy number variations were obtained from the UCSC (University of California, Santa Cruz) Xena database. We curated 21 m6A regulators and performed consensus clustering analysis to quantify the m6A modification pattern.

Of the 184 patients, 23 (12.5%) were genetically altered in m6A regulators, with the highest frequency of mutations in ZC3H13 and LRPPRC. We constructed a m6A score system to investigate the prognosis of ESCA. The m6A score was closely related to immune cell infiltration in the tumor immune microenvironment. Patients with a high m6A score had an unfavorable prognosis. The combination of tumor mutation burden and m6A score would improve the prognostic value.

Our study established and validated a strong prognostic signature based on m6A regulators. This can be used to accurately predict the prognosis of ESCA.

Esophageal cancer (EC) is a highly prevalent and progressive disease. Early prediction of EC risk in the population is crucial in preventing this disease and enhancing the overall health of individuals. So far, few studies have been conducted on predicting the EC risk based on the prediction models, and most of them focused on statistical methods. The ML approach obtained efficient predictive insights into the clinical domain. Therefore, this study aims to develop a risk prediction model for EC based on risk factors and by leveraging the ML approach to stratify the high-risk EC people and obtain efficient preventive purposes at the community level.

The current retrospective study was performed from 2018 to 2022 in Sari City based on 3256 EC and non-EC cases. The six selected algorithms, including Random Forest (RF), eXtreme Gradient Boosting (XG-Boost), Bagging, K-Nearest Neighbor (K-NN), Support Vector Machine (SVM), and Artificial Neural Networks (ANNs), were used to develop the risk prediction model for EC and achieve the preventive purposes.

Comparing the performance efficiency of algorithms revealed that the XG-Boost model gained the best predictability for EC risk with AU-ROC = 0.92 and AU-ROC-test = 0.889 for internal and validation states, respectively. Based on the XG-Boost, the factors, including sex, drinking hot liquids, fruit consumption, achalasia, and vegetable consumption, were considered the five top predictors of EC risk.

This study showed that the XG-Boost could provide insight into the early prediction of the EC risk for people and clinical providers to stratify the high-risk group of EC and achieve preventive measures based on modifying the risk factors associated with EC and other clinical solutions.

Esophageal carcinoma (EC) is a prominent contributor to cancer-related mortality since it lacks discernible features in its first phases. Multiple studies have shown that narrow-band imaging (NBI) has superior accuracy, sensitivity, and specificity in detecting EC compared to white light imaging (WLI). Thus, this study innovatively employs a color space linked to décor to transform WLIs into NBIs, offering a novel approach to enhance the detection capabilities of EC in its early stages. In this study a total of 3415 WLI along with the corresponding 3415 simulated NBI images were used for analysis combined with the YOLOv5 algorithm to train the WLI images and the NBI images individually showcasing the adaptability of advanced object detection techniques in the context of medical image analysis. The evaluation of the model's performance was based on the produced confusion matrix and five key metrics: precision, recall, specificity, accuracy, and F1-score of the trained model. The model underwent training to accurately identify three specific manifestations of EC, namely dysplasia, squamous cell carcinoma (SCC), and polyps demonstrates a nuanced and targeted analysis, addressing diverse aspects of EC pathology for a more comprehensive understanding. The NBI model effectively enhanced both its recall and accuracy rates in detecting dysplasia cancer, a pre-cancerous stage that might improve the overall five-year survival rate. Conversely, the SCC category decreased its accuracy and recall rate, although the NBI and WLI models performed similarly in recognizing the polyp. The NBI model demonstrated an accuracy of 0.60, 0.81, and 0.66 in the dysplasia, SCC, and polyp categories, respectively. Additionally, it attained a recall rate of 0.40, 0.73, and 0.76 in the same categories. The WLI model demonstrated an accuracy of 0.56, 0.99, and 0.65 in the dysplasia, SCC, and polyp categories, respectively. Additionally, it obtained a recall rate of 0.39, 0.86, and 0.78 in the same categories, respectively. The limited number of training photos is the reason for the suboptimal performance of the NBI model which can be improved by increasing the dataset.

Cancer is a global health challenge with high morbidity and mortality rates. However, conventional cancer treatment methods often have severe side effects and limited success rates. In the last decade, extensive research has been conducted to develop safe, and efficient alternative treatments that do not have the limitations of existing anticancer medicines. Plant-derived compounds have shown promise in cancer treatment for their anti-carcinogenic and anti-proliferative properties. Rosmarinic acid (RA) and carnosic acid (CA) are potent polyphenolic compounds found in rosemary (Rosmarinus officinalis) extract. They have been extensively studied for their biological properties, which include anti-diabetic, anti-inflammatory, antioxidant, and anticancer activities. In addition, RA and CA have demonstrated effective anti-proliferative properties against various cancers, making them promising targets for extensive research to develop candidate or leading compounds for cancer treatment. This review discusses and summarizes the anti-tumor effect of RA and CA against various cancers and highlights the involved biochemical and mechanistic pathways.

Esophageal cancer was the eighth and sixth leading cause of morbidity of all cancers in the world, and the 15th and 12th in Ethiopia, respectively. There is a lack of comprehensive data regarding Ethiopia's esophageal cancer hotspot, treatment outcome clustering, and other factors.

This scoping review was designed to understand the extent and type of existing evidence regarding spatiotemporal distribution, time to treatment outcome clustering, and determinants of esophageal cancer in Ethiopia up to March 28, 2023.

Three-step search strategies were employed for the scoping review from March 15 to 28, 2023. Targeted databases included PubMed/Medline, PubMed Central (PMC), Google Scholar, Hinari, and Cochrane for published studies and different websites for unpublished studies for evidence synthesis. Data were extracted using the Joanna Briggs Institute (JBI) manual format.

Our final analysis comprised 17 (16 quantitative and 1 qualitative) studies. Three studies attempted to depict the country's temporal distribution, whereas 12 studies showed the spatial distribution of esophageal cancer by proportion. The regional state of Oromia recorded a high percentage of cases. Numerous risk factors linked to the tumor have been identified in 8 investigations. Similarly, 5 studies went into detail regarding the likelihood of survival and the factors that contribute to malignancy, while 2 studies covered the results of disease-related treatments.

The substantial body of data that underpins this finding supports the fact that esophageal cancer has several risk factors and that its prevalence varies greatly across the country and among regions. Surgery, radiotherapy, or chemotherapy helped the patient live longer. However, no research has investigated which treatment is best for boosting patient survival and survival clustering. Therefore, research with robust models for regional distribution, clustering of time to treatment outcomes, and drivers of esophageal cancer will be needed.

Esophageal cancer (EC) is a challenging tumor to treat with radiotherapy, often exhibiting resistance to this treatment modality. To explore the factors influencing radioresistance, we focused on the role of hypoxia-induced factor-1α (HIF-1α), and its interaction with the long noncoding RNA long intergenic nonprotein coding RNA 1116 (LINC01116). We analyzed the LINC01116 expression in EC and EC cell lines/human normal esophageal epithelial cell line (Het-1A). LINC01116 was silenced/overexpressed in EC109/KYSE30 cells under hypoxia, followed by radioresistance assessment. We measured HIF-1α levels in hypoxic EC cells and further validated the binding of HIF-1α with LINC01116, analyzing their interaction in EC cells. We then performed experiments in EC109 cells by transfection them with sh-HIF-1α/oe-LINC01116 to verify the effects. Additonally, we analyzed the localization of LINC01116 and its binding with miR-3612, followed by a combined experiment performed to validate the results. Our findings indicated that LINC01116 was highly expressed in EC and further elevated in hypoxic EC cells. LINC01116 was expressed at a high level in EC, which was further elevated in EC cells under hypoxic conditions. Knockdown of LINC01116 triggered EC cell apoptosis, thus suppressing radioresistance. Further investigation revealed that HIF-1α transcriptionally activated LINC01116 expression under hypoxia, and silencing HIF-1α lowered EC cell radioresistance by downregulating LINC01116. Under hypoxic conditions, LINC01116 could function as a sponge for miR-3612 and inhibit its expression. This interaction between LINC01116 and miR-3612 played a crucial role in mediating radioresistance in EC cells. Briefly, under hypoxic conditions, HIF-1α facilitates radioresistance of EC cells by transcriptionally activating LINC01116 expression and downregulating miR-3612.

Cuproptosis involves a direct interaction with the tricarboxylic acid (TCA) lipid acylation components. This process intricately intersects with post-transcriptional lipid acylation (LA) and is linked to mitochondrial respiration and LA metabolism. Copper ions form direct bonds with acylated DLAT, promoting DLAT oligomerization, reducing Fe-S cluster proteins, and inducing a protein-triggered toxic stress response that culminates in cell demise. Simultaneously, the importance of immune contexture in cancer progression and treatment has significantly increased. We assessed the expression of cuproptosis-related genes (CRGs) across TCGA and validated our findings using the GEO data. Consensus clustering divided esophageal cancer (ESCA) patients into two clusters based on the expression of 7 CRGs. We evaluated the expression of immune checkpoint inhibitor (ICI) targets and calculated the elevated tumor mutational burden (TMB). Weighted gene co-expression network analysis (WGCNA) identified genes associated with the expression of CRGs and immunity. Cluster 1 exhibited increased immune infiltration, higher expression of ICI targets, higher TMB, and a higher incidence of deficiency in mismatch repair-microsatellite instability-high status. WGCNA analysis identified 14 genes associated with the expression of CRGs and immune scores. ROC analysis revealed specific hub genes with strong predictive capabilities. The expression levels of SLC6A3, MITD1, and PDHA1 varied across different pathological stages; CCS, LIPT2, PDHB, and PDHA1 showed variation in response to radiation therapy; MITD1 and PDHA1 exhibited differences related to the pathological M stages of ESCA. CRGs influence the immune contexture and can potentially transform cold tumors into hot tumors in ESCA patients.

Gastrointestinal cancers are a specific group of oncological diseases in which the location and nature of growth are of key importance for clinical symptoms and prognosis. At the same time, as research shows, they pose a serious threat to a patient's life, especially at an advanced stage of development. The type of therapy used depends on the anatomical location of the cancer, its type, and the degree of progression. One of the modern forms of therapy used to treat gastrointestinal cancers is PDT, which has been approved for the treatment of esophageal cancer in the United States. Despite the increasingly rapid clinical use of this treatment method, the exact immunological mechanisms it induces in cancer cells has not yet been fully elucidated. This article presents a review of the current understanding of the mode of action of photodynamic therapy on cells of various gastrointestinal cancers with an emphasis on colorectal cancer. The types of cell death induced by PDT include apoptosis, necrosis, and pyroptosis. Anticancer effects are also a result of the destruction of tumor vasculature and activation of the immune system. Many reports exist that concern the mechanism of apoptosis induction, of which the mitochondrial pathway is most often emphasized. Photodynamic therapy may also have a beneficial effect on such aspects of cancer as the ability to develop metastases or contribute to reducing resistance to known pharmacological agents.