crossing96/oncoscreening huggingface dataset:
Induction of miR-224 by Reactive Oxygen Species Regulates RASSF6 and Thus Modulates Malignant Behaviors and Chemosensitivity in Esophageal Squamous Cell Carcinoma.	Esophageal cancer is one of the most common malignant tumors of the digestive tract, and miR-224 can promote the hypoxia tolerance of esophageal cancer cells. The expression of miR-224 and HIF-1α in esophageal cancer cells under hypoxic induction and their relationship with ROS was studied using RT-qPCR and Western Blot assays; cell viability and apoptosis under hypoxia, as well as the effects of miR-224 on cell proliferation and drug resistance, were investigated using CCK8, Annexin V-FITC/PI, H2DCFDA staining and Western Blot assays. Under hypoxic induction, miR-224 and HIF-1α expressions were upregulated, with the upregulation of miR-224 being related to ROS accumulation, while HIF-1α upregulation was not affected by ROS. Furthermore, the upregulation of miR-224 facilitated the survival of esophageal cancer cells under hypoxic conditions and reduced their chemosensitivity to CDDP. This effect was also validated in vitro, as miR-224 overexpression promoted the malignant behaviors in ESCC cells. Under hypoxic induction, ROS accumulation can lead to the upregulation of miR-224. MiR-224 facilitates the survival of esophageal cancer cells under hypoxic conditions and induces chemotherapeutic drug resistance.	esophagus
Epidural analgesia during esophagectomy and esophageal cancer prognosis: A population-based nationwide study in Finland.	BACKGROUND: The use of epidural analgesia has been proposed to improve the prognosis of esophageal cancer by attenuating the stress response and being less immunosuppressive than opioids. This study aims to evaluate the association, if any, between non-epidural pain management compared to epidural analgesia during minimally invasive or open esophagectomy and esophageal cancer prognosis. MATERIALS AND METHODS: This was a population-based nationwide retrospective cohort study in Finland, using the Finnish National Esophago-Gastric Cancer Cohort (FINEGO). Esophagectomy patients with epidural and no epidural analgesia were compared. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI) non-epidural pain management compared to epidural analgesia, adjusted for the calendar period of surgery, sex, age, comorbidity (Charlson Comorbidity Index), tumor stage, tumor histology, neoadjuvant therapy, type of surgery, and esophageal cancer surgery volume. RESULTS: After exclusions, there were 1381 patients available with information on epidural analgesia. Of these, 969 (70.2%) were men and 832 (60.2%) had esophageal adenocarcinoma. After adjustment for confounding factors, non-epidural pain management was not associated with higher 90-day mortality (HR 1.022 95% CI 0.582-1.794), overall mortality up to 5 years (HR 1.156 95% CI 0.909-1.470), nor with 5 years cancer-specific mortality (HR 1.134 95% CI 0.884-1.456) compared to epidural analgesia. CONCLUSION: Although the point estimates may hint at a potentially improved prognosis associated with epidural use, this population-based nationwide study suggests no statistically significant association between epidural analgesia during esophagectomy and esophageal cancer prognosis. EDITORIAL COMMENT: This large esophagectomy (cancer) cohort in Finland was used to compare those who received epidural analgesia with those who did not for associations with late mortality in a retrospective analysis and where anesthesia and analgesia treatments were not controlled. The findings showed that when other recognized risks for mortality were taken into account, there was not a meaningful difference in relative risk for late mortality related to the presence or absence of epidural analgesia, though the analgesia treatments were not randomly allocated. These results do not rule out associations of analgesia choice with other outcomes that might be important to patients.	esophagus
Survival benefits of postoperative radiotherapy in esophageal cancer during the immunotherapy era:a retrospective cohort study based on the SEER database and a single-center registry in China.	PURPOSE: The aim of this study was to investigate the survival benefits of postoperative radiotherapy (PORT) in patients with resectable esophageal cancer (EC) after neoadjuvant therapy in the Immunotherapy era. METHODS: The study was designed as a retrospective cohort study, which included a total of 733 patients with EC from the SEER database and a single-center cohort. We used propensity score matching (PSM) to equilibrate patient characteristics. The investigation incorporated Kaplan-Meier survival analysis and the Cox proportional risk regression model to assess outcomes. RESULTS: PORT did not significantly improve survival in the overall cohort, with a median overall survival of 38 months (p=0.56) in the SEER cohort and 39 months (p=0.75) in the Chinese cohort. However, in the immunotherapy subgroup, the Chinese cohort demonstrated that immunotherapy combined with PORT significantly improved survival (p=0.044).Multivariate Cox regression analysis demonstrated that patients aged 50-59 years (HR=5.93, 95% CI: 1.67-21.06) and those aged ≥70 years (HR=10.96, 95% CI:3.04-39.56) had increased survival risks compared to patients aged <50 years. Additionally, ypT3-4 stage patients exhibited a higher risk than those with ypT1-2 stage (HR=2.12, 95% CI: 1.14-3.93, p=0.017).Similar trends were observed in cT3-4 staging, R1/R2 and no immunotherapy. Lymph node metastasis also showed a progressive relationship with survival risk, with patients categorized as ypN1 (HR=1.90), ypN2 (HR=4.24), and ypN3 (HR=6.68) experiencing increasingly higher risks (p<0.05). CONCLUSIONS: The collaborative effect of immunotherapy and PORT potentially enhances survival outcomes for patients with EC. However, further prospective research is essential to confirm our results.	esophagus
Unveiling SSR4: a promising biomarker in esophageal squamous cell carcinoma.	BACKGROUND: Esophageal squamous cell carcinoma (ESCC) represents a frequent cancer with a poor prognosis. Altered glucose metabolism contributes factor to ESCC progression. In our previous study, signal sequence receptor subunit delta (SSR4) was included in an ESCC prognostic model; however, the mechanisms underlying SSR4 implication in ESCC remain ambiguous. Accordingly, we aim to determine the interconnection between SSR4 expression and clinical characteristics of ESCC. METHODS: This differential expression and prognostic significance of SSR4 was performed using bulk RNA-seq data and 110 patients with complete follow-up information. The ESCC cell subsets with the highest gene expression levels were identified with single-cell data. Gene function and enrichment, immune infiltration, cell communication, and molecular docking analyses were performed. RESULTS: Unlike adjacent non-cancerous tissues, SSR4 was overexpressed in ESCC tissues, validated by both reverse transcription-qPCR and IHC staining. SSR4 expression was related to the N stage, lymph node metastasis, and AJCC TNM classification stage. Patients exhibiting low SSR4 expression had a more favorable prognosis. The highest SSR4 expression was recognized in tumor plasma cells. Continued exploration of immune infiltration highlighted a close association between SSR4 gene expression and the infiltration of immune cells such as plasma cells. On dividing cells into SSR4-positive and -negative groups, CellChat analysis indicated that SSR4 may regulate the interactions that existed between ESCC tumor plasma cells and the tumor microenvironment (TME) by modulating the MIF/CD74/CXCR4 axis. CONCLUSION: The SSR4 gene may have significant relevance with clinical pathological factors, and play a critical role in the regulation of tumor microenvironment of ESCC patients. Overall, SSR4 may be a promising ESCC biomarker with prospective applicability in clinical diagnosis as well as the development of targeted treatment approaches in patients of ESCC.	esophagus
Identification of biomarkers and potential drug targets for esophageal cancer: a Mendelian randomization study.	Esophageal cancer (EC) is a common and deadly malignancy of the digestive system. Currently, effective treatments for EC are limited and patient prognosis remains poor. In this study, we utilized Mendelian Randomization (MR) to identify potential drug targets for EC by analyzing proteins linked to the disease risk. A total of 734 plasma proteins and 4,479 druggable genes were obtained from recent studies, and two-sample MR analyses were conducted to investigate causal relationships between these proteins and EC. The cis-pQTL data of the proteins was analyzed after filtering. The inverse variance weighted (IVW) method was the primary analytical approach in MR analysis. Steiger filtering, heterogeneity and pleiotropy tests, Summary-data-based Mendelian Randomization (SMR) analysis, and Bayesian co-localization analysis were implemented to consolidate the results further. Moreover, drugs corresponding to the identified proteins were found in the DrugBank database. Five proteins HPSE, ST3GAL1, CEL, KLK13, and GNRH2 were identified as highly associated with EC. HPSE and GNRH2 showed protective effects with odds ratios (OR) of 0.80 (95% confidence interval [CI], 0.70-0.92) and 0.73 (95% CI 0.54-0.98), respectively. In contrast, increased expression of ST3GAL1(OR, 1.37; 95% CI 1.04-1.82), CEL (OR, 1.27; 95% CI 1.08-1.49), and KLK13 (OR, 1.22; 95% CI 1.04-1.42) were all associated with a higher risk of EC. In addition, the HPSE protein showed moderate colocalization with EC [coloc.abf-posterior probability of hypothesis 4 (PPH4) = 0.637]. Furthermore, the sensitivity analyses indicated no heterogeneity or pleiotropy. Therefore, these findings present promising drug targets for EC and deserve further clinical investigation.	esophagus
Discovery of 4-(2-(methylamino)thiazol-5-yl)pyrimidin-2-amine derivatives as novel cyclin-dependent kinase 12 (CDK12) inhibitors for the treatment of esophageal squamous cell carcinoma.	The transcriptional cyclin-dependent protein kinase 12 (CDK12), a potential target in various cancers, was recently discovered with a dramatic amplification in esophageal cancer (EC). In this study, we conducted an online database analysis that revealed CDK12 to be overexpressed in esophageal squamous cell carcinoma (ESCC) tissue samples from patients. Furthermore, survival analysis indicated that CDK12 can serve as a prognostic indicator for ESCC patients. In addition, CDK12 knockdown had been shown to reduce the proliferation of ESCC cells. The present study also details the design, synthesis, and biological evaluation of new CDK12 inhibitors which bear the scaffold of 4-(2-(methylamino)thiazol-5-yl)pyrimidin-2-amine. Among the synthesized compounds, H63 has been identified as a potent inhibitor of CDK12 with excellent anti-ESCC activity. Mechanistically, H63 blocked transcription elongation, downregulated the G1-phase core genes to induce cell cycle arrest, and altered the CDK12-ATM/ATR-CHEK1/CHEK2 signaling axis to cause DNA damage. In addition, H63 exhibited favorable pharmacokinetic properties, good safety, and prominent anti-ESCC activity in vivo. The present study suggests that CDK12 is a promising target for ESCC treatment, and H63 is a promising candidate for further clinical development as an anti-ESCC drug.	esophagus
The efficacy and safety of FOLFOX therapy for advanced esophageal squamous cell carcinoma.	Cisplatin-based chemotherapy is the standard advanced esophageal squamous cell carcinoma (ESCC) treatment. However, the 5-fluorouracil plus L-leucovorin and oxaliplatin (FOLFOX) regimen is available in Japan as an alternative to cisplatin-based chemotherapy, but its efficacy and safety remain unclear. Hence, we aimed to evaluate patients with advanced ESCC who received FOLFOX therapy retrospectively. Patients with advanced ESCC who received FOLFOX therapy at 18 institutions between April 2019 and October 2020 were included. Fifty-two patients received first-line FOLFOX treatment, while 39 received later-line FOLFOX treatment. The median progression-free survival, median overall survival, and objective response rate were 3.8 months (95% confidence interval [CI]: 3.0-5.0), 13.9 months (95% CI: 10.3-17.9 months), and 35% in the first-line group and 2.4 months (95% CI: 2.1-3.8 months), 7.2 months (95% CI: 5.3-9.8 months), and 4% in the later-line group, respectively. The most frequent grade 3 or 4 adverse events were neutropenia (23%) and anemia (12%) in the first-line group and neutropenia (18%), anorexia (13%), anemia (10%), and nausea (10%) in the later-line group. First-line FOLFOX treatment is suitable for patients with advanced ESCC. However, FOLFOX has shown limited efficacy as a later-line treatment.	esophagus
Radiation Dose-Volume Effects on Negative Tumor-Draining Lymph Nodes Affected T-cell Activation and Prognosis in Esophageal Cancer with Chemoradiotherapy.	PURPOSE: A preclinical model found that elective nodal irradiation attenuated the efficacy of radiotherapy (RT) and radio-immunotherapy. However, limited clinical studies have explored the correlation between radiation dose-volume parameters of negative tumor-draining lymph nodes (TDLN) and T-cell activation/prognosis for patients with cancer treated with definitive radiochemotherapy. EXPERIMENTAL DESIGN: Patients with locally advanced esophageal cancer undergoing definitive chemoradiotherapy (CRT) were selected from two prospective trials. Dose-volume parameters of TDLN as well as other lymphocyte-related organs at risk and lymphocyte subsets such as CD3-CD19+ B cells, CD8+CD28+ T cells, and activated T cells (CD3+CD8+HLA-DR+) before and at the end of RT were collected. Logistic analysis was utilized to correlate dose-volume parameters with reductions in lymphocyte subsets. Prognosis of TDLN irradiation was investigated through Kaplan-Meier analysis and Cox hazards models. RESULTS: Among 512 patients, the median mean dose of TDLN and negative non-TDLN was 25.6 and 15.1 Gy, respectively. Multivariable analyses indicated that TDLN V15 >50% was an independent predictor of poorer local recurrence-free survival (HR, 1.31; P = 0.029) and distant metastasis-free survival (HR, 1.39; P < 0.001), as well as greater reductions in CD3-CD19+ B cells (OR, 1.98; P = 0.002), CD8+CD28+ T cells (OR, 3.42; P < 0.001), and CD3+CD8+HLA-DR+ T cells (OR, 4.67; P = 0.002) after RT. CONCLUSIONS: A higher radiation dose-volume parameter of TDLNs in patients with esophageal cancer undergoing CRT was significantly associated with suppression of T-cell activation and a worse prognosis. Limiting the percentage of TDLN V15 may be beneficial for improving the prognosis of CRT with or without PD-1 inhibitors.	esophagus
High Risk of Persistence and Risk of Dysplasia After Diagnosis of Ultrashort Barrett's Esophagus.	INTRODUCTION: The management of ultrashort (<1 cm) Barrett's esophagus (BE) remains unclear. We aimed to determine the prevalence of ultrashort BE (USBE) at index diagnosis, identify factors associated with persistent BE after USBE diagnosis, and identify risk of dysplasia after initial USBE in a population of US veterans. METHODS: This was a retrospective cohort study at the Veterans Affairs hospital in Houston, TX, of consecutive patients with new BE diagnosis from November 1990 to June 2022 with follow-up through April 2023. Using a pathology database, we identified patients with a new USBE diagnosis and any subsequent follow-up esophagogastroduodenoscopy (EGD). We examined the association of sociodemographic and clinical risk factors of persistent USBE cohort compared with longer-length segment BE and those with a negative follow-up EGD after index USBE with χ 2 tests and logistic regression models. Last, we calculated the prevalence and incidence of any dysplasia in persistent BE after USBE at index diagnosis compared with BE ≥1 cm. We excluded patients without at least 1 follow-up endoscopy. RESULTS: Of 739 patients with BE, 167 (22.6%) had USBE on index EGD. Of those with index USBE, 86 (51.5%) had persistent BE and 67 (40.1%) had negative intestinal metaplasia on follow-up EGD. There was a greater proportion of non-Hispanic White and Hispanic than non-Hispanic Black patients with persistent BE after index USBE and the negative follow-up of EGD cohorts ( P = 0.012), but no significant difference in age, sex, smoking status, alcohol status, and body mass index between the 2 groups. White race (adjusted odds ratio [aOR] 3.80; 95% confidence interval [CI] 1.35-10.7) and Hispanic ethnicity (aOR 4.85; 95% CI 1.19-19.7; ref: non-Hispanic Black) were associated with an increased likelihood of persistent BE. During 3,880.7 person-years of follow-up, 112 patients (10 persistent BE after index USBE) developed definite dysplasia/neoplasia. The incidence rate of definite dysplasia/neoplasia was 19.5 per 1,000 person-years (95% CI 10.5-36.3 per 1,000 person-years) in those with persistent BE after USBE and 33.8 per 1,000 person-years (95% CI 27.9-41.1 per 1,000 person-years) in those with longer segment BE ( P value by log-rank test = 0.23; hazard ratio 0.67; 95% CI 0.35-1.29). We did not identify any significant predictors of dysplasia in persistent BE after index endoscopy with USBE. DISCUSSION: The prevalence of persistent BE after index USBE is high, and there is a risk of developing dysplasia/neoplasia in persistent BE after USBE. We were unable to detect a difference in the risk of dysplasia/neoplasia between persistent BE after index USBE and BE ≥1 cm on index endoscopy in a cohort of US veterans. White race and Hispanic ethnicity are associated with persistent BE after index USBE and may be target demographics for surveillance.	esophagus
[The role of surgery in preventing esophageal cancer].	The prognosis for esophageal cancer remains poor because it is often diagnosed late and patients often have unfavourable backgrounds. This is reflected in standardised 5-year net survival rates of no more than 20%, regardless of gender. Unlike gastric cancer (CDH1 gene mutation), there is currently no genetic predisposition to esophageal cancer that would justify prophylactic esophagectomy. Primary prevention by identifying and managing modifiable risk factors is therefore the best strategy for preventing esophageal cancer. The role of surgery in the prevention of esophageal cancer is discussed in this review. Although recommended, the value of antireflux surgery (fundoplication) for Barrett's esophagus with the sole aim of reducing the risk of esophageal adenocarcinoma remains controversial. With regard to bariatric surgery, national cohort studies report an equivalent or reduced incidence of esophageal adenocarcinoma in operated patients compared with non-operated obese patients. However, given the significant increase in the number of bariatric procedures, further studies with longer follow-up are needed. In addition, although surgical myotomy is a truly effective therapeutic option for the treatment of achalasia in the first-line setting, its impact on the risk of esophageal cancer remains uncertain and poorly studied.	esophagus
Artificial Intelligence Applications in Image-Based Diagnosis of Early Esophageal and Gastric Neoplasms.	"Artificial intelligence (AI) holds the potential to transform the management of upper gastrointestinal (GI) conditions, such as Barrett's esophagus, esophageal squamous cell cancer, and early gastric cancer. Advancements in deep learning and convolutional neural networks offer improved diagnostic accuracy and reduced diagnostic variability across different clinical settings, particularly where human error or fatigue may impair diagnostic precision. Deep learning models have shown the potential to improve early cancer detection and lesion characterization, predict invasion depth, and delineate lesion margins with remarkable accuracy, all contributing to effective treatment planning. Several challenges, however, limit the broad application of AI in GI endoscopy, particularly in the upper GI tract. Subtle lesion morphology and restricted diversity in training datasets, which are often sourced from specialized centers, may constrain the generalizability of AI models in various clinical settings. Furthermore, the ""black box"" nature of some AI systems can impede explainability and clinician trust. To address these issues, efforts are underway to incorporate multimodal data, such as combining endoscopic and histopathologic imaging, to bolster model robustness and transparency. In the future, AI promises substantial advancements in automated real-time endoscopic guidance, personalized risk assessment, and optimized biopsy decision making. As it evolves, it would substantially impact not only early diagnosis and prognosis, but also the cost-effectiveness of managing upper GI diseases, ultimately leading to improved patient outcomes and more efficient health care delivery."	esophagus
Circ_DLG1 facilitates cell proliferation and metastasis of esophageal squamous cell carcinoma via upregulating MAP3K9.	BACKGROUND: Circ_DLG1 is found to be aberrantly expressed in esophageal squamous cell carcinoma (ESCC) tissues, but its role in the progression of ESCC remains to be elucidated. METHODS: The expression of circ_DLG1, miR-338-3p and mitogen-activated protein kinase kinase kinase 9 (MAP3K9) was measured by qRT-PCR. Cell cycle, viability, migration and invasion were investigated using flow cytometry, MTT assay and transwell assay, respectively. The protein levels of MAP3K9, p38, phosphor p38 (p-p38), ERK1/2 (ERKs), phosphor ERKs (p-ERKs) were detected by western blot. Dual-luciferase reporter assay and RIP assay were performed to verify the putative relationship between miR-338-3p and circ_DLG1 or MAP3K9. Animal experiments were performed to ascertain the role of circ_DLG1 in vivo. RESULTS: Circ_DLG1 expression was elevated in ESCC tissues, plasma and cells. Circ_DLG1 knockdown inhibited cell proliferation, migration and invasion. MAP3K9 was highly expressed in ESCC, and its overexpression rescued the effects of circ_DLG1 knockdown on cell proliferation and metastasis. Besides, circ_DLG1 positively regulated MAP3K9 expression by competitively targeting miR-338-3p. Also, miR-338-3p inhibition or MAP3K9 overexpression recovered the inhibiting effect of circ_DLG1 knockdown on the phosphorylated levels of p38 and ERKs. In addition, circ_DLG1 knockdown blocked the tumor growth in vivo by regulating the miR-338-3p/MAP3K9 axis. CONCLUSION: Circ_DLG1 promoted malignant progression of ESCC by mediating the miR-338-3p/MAP3K9/p38/ERK pathway, indicating that targeted inhibition of the circ_DLG1/miR-338-3p/MAP3K9/p38/ERK axis might be an effective strategy for the treatment of ESCC.	esophagus