crossing96/oncoscreening huggingface dataset:
FOXD2-AS1 is modulated by METTL3 with the assistance of YTHDF1 to affect proliferation and apoptosis in esophageal cancer.	This study aims to investigate the regulatory mechanisms of METTL3, YTHDF1, and the long non-coding RNA FOXD2-AS1 in the proliferation and apoptosis of esophageal cancer, with the goal of providing a basis for molecular diagnosis and targeted therapies. Gene expression was evaluated using qRT-PCR (METTL3/14) and Western blot analysis. The Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and Transwell assay were employed to assess cell proliferation and apoptosis. The EpiQuik m6A RNA Methylation Quantification Kit was utilized to quantify total m6A levels. The interaction between YTHDF1, FOXD2-AS1, and METTL3 was confirmed using RNA Binding Protein Immunoprecipitation (RIP), Co-Immunoprecipitation (CO-IP), and RNA pull-down assays. Methylated RNA Immuno preci pitation (MeRIP) was employed to assess the m6A modification levels of FOXD2-AS1. Tissue samples from animal models were analyzed via Hematoxylin-eosin staining (HE) staining and immunohisto-chemistry to assess METTL3 expression. The expression of METTL3 was up-regulated in esophageal cancer tissues and cells. Flow cytometry and CCK-8 detection showed that silencing METTL3 could inhibit the proliferation of esophageal cancer cells but accelerate their apoptosis. MeRIP-qPCR and Prediction of m6A-modified sites indicated that METTL3 regulated the m6A modification of FOXD2-AS1. In vitro and in vivo experiments showed that YTHDF1 binds to METTL3 and regulates the m6A modification of FOXD2-AS1 to affect esophageal cancer. Our results indicate that METTL3 regulates FOXD2-AS1 in an m6A-dependent manner through its interaction with YTHDF1, thereby influencing EC proliferation and apoptosis. This suggests a potential therapeutic target for the treatment of esophageal cancer.	esophagus
Regulatory T Cell Infiltration-Driven Single-Cell Transcriptomic Analysis Identifies SAP18 as a Prognostic Marker for Esophageal Squamous Cell Carcinoma.	BACKGROUND: Advanced esophageal squamous cell carcinoma (ESCC) is characterized by molecular heterogeneity and distinct patterns of immune cell infiltration. Regulatory T cells (Tregs), in particular, play a critical role in shaping an immunosuppressive tumor microenvironment (TME), which is associated with poor clinical outcomes. METHODS: We developed a prognostic model by integrating GEO-derived bulk RNA sequencing data and single-cell transcriptome. Model predictions were confirmed through RT-qPCR, Western blot, and immunohistochemistry on clinical specimens, while in vitro assays (CCK8, transwell invasion, scratch, colony formation, and immunofluorescence) validated the function of SAP18 in cell proliferation, invasion, and ECM remodeling. RESULTS: Expression patterns of the 5 Tregs-associated genes in clinical specimens aligned with model predictions, underscoring the model's robustness. The high-risk subgroup was associated with upregulated extracellular matrix (ECM) remodeling, an abundance of immune-suppressive cells, higher TP53 mutation rate, and limited benefit from immunotherapy. In contrast, the low-risk subgroup exhibited anti-tumor immunity. Cell-cell communication analysis also implicated the collagen pathway in Tregs-mediated immune evasion in ESCC. Functional assays indicated that SAP18 in the prognostic model significantly promotes proliferation, invasion, and ECM reconstruction, further highlighting its potential as a therapeutic target. CONCLUSION: Our findings elucidate the role of Tregs in the TME, underscoring significant potential of SAP18, which is essential for assessing patient prognosis and may facilitate the development of personalized therapies for ESCC.	esophagus
Relationship of phase angle with postoperative pneumonia and survival prognosis in patients with esophageal cancer: A retrospective cohort study.	OBJECTIVES: Phase angle (PhA), derived from bioelectrical impedance analysis (BIA), is an indicator of cell membrane health. Low PhA values reflect poor cellular function and low muscle mass. However, consensus regarding the appropriate cutoff value of PhA remains insufficient, and its impact on outcomes after esophagectomy in patients with esophageal malignancies is not well studied. We aimed to investigate whether preoperative PhA is associated with postoperative complication risk and survival prognosis and whether PhA decrease during the surgical preparation period is a prognostic factor in patients with esophageal cancer. METHODS: This retrospective cohort study analyzed data from 194 patients who had undergone esophagectomy for esophageal malignancies. A PhA measured several days before surgery, with cutoff values of 5.0° for men and 4.2° for women, was used. The relationship between postoperative pneumonia and clinicopathological factors and between low PhA and postoperative outcomes and survival prognosis was investigated. The preoperative PhA decline and survival prognosis were analyzed in 134 patients whose PhA was measured twice before surgery. RESULTS: Overall, 93 and 101 patients were classified into the low and high PhA groups, respectively. A multivariate analysis showed that a serum albumin level lower than 3.5 g/dL and low PhA were independent risk factors for pneumonia (odds ratio [OR] = 3.40, P = 0.03; OR = 3.42, P = 0.03, respectively). The low PhA group exhibited significantly higher intraoperative fluid balance (6.7 versus 6.0 mL/kg/h, P = 0.01) and a higher proportion of patients who failed to achieve early mobilization on the first postoperative day (46 versus 32%, P = 0.04) than did the high PhA group. Multivariate analysis using a Cox proportional hazards model revealed that low PhA was a poor survival prognostic factor, independent of the clinical stage of esophageal cancer (hazard ratio = 2.61, P < 0.01). In patients whose PhA was measured twice preoperatively, a decrease in PhA during the preoperative period was a significant indicator of poor survival (hazard ratio = 2.59, P < 0.01). The group with a decrease in PhA during the preoperative period had significantly fewer steps than the group with an increase in PhA (6220 ± 2880 versus 8200 ± 2850, P < 0.01). CONCLUSIONS: Low PhA was a risk factor for postoperative pneumonia in patients who had undergone esophagectomy and was associated with poor survival prognosis. A decrease in PhA during the preoperative period was a significant poor prognostic factor. Increasing physical activity before surgery may lead to an increase in PhA. Thus, it is important to measure and evaluate PhA changes sequentially in patients with esophageal cancer.	esophagus
Trifluridine/Tipiracil and Oxaliplatin as Induction Chemotherapy in Resectable Esophageal and Gastroesophageal Junction Adenocarcinoma: A Phase II Study.	BACKGROUND: Preoperative chemoradiation (CRT) followed by surgery for localized esophageal and gastroesophageal junction adenocarcinoma (EGAC) is a standard of care with a pathologic complete response (pCR) rate of 20%. We evaluated a novel combination of trifluridine/tipiracil with oxaliplatin as induction chemotherapy (IC) followed by CRT. METHODS: We enrolled patients with potentially resectable localized EGAC (T3, T4aN0, or node-positive disease) in this open-label, single-arm, multicenter, Phase II trial between January 2020 and October 2022. Patients received three cycles of IC with trifluridine/tipiracil and oxaliplatin and then underwent concurrent CRT with weekly carboplatin and paclitaxel followed by surgery. The primary objective was to evaluate the pCR rate. The secondary objectives were to evaluate 2-year progression-free survival (PFS), 2-year overall survival (OS), and toxicities. Circulating tumor DNA (ctDNA) was measured at prespecified intervals to assess its correlation with clinical outcomes. RESULTS: Of the 22 enrolled patients, 19 (86.4%) were male and 20 (90.9%) were Caucasian. The median age was 61 years, and 12 (54.5%) had their primary disease at the gastroesophageal junction. Twenty (90.9%) patients had T3 disease, and 15 (68.2%) had node-positive disease. Only two patients had pCRs, and an additional five had near pCRs. Since we could not meet our predefined pCR rate at the interim analysis, the study was closed. After a median follow-up of 15.8 months, 2-year OS and PFS were 43% and 41%, respectively. ctDNA clearance was associated with a significantly higher OS rate (p = 0.012) and PFS rate (p = 0.008). Nausea (59.1%) and fatigue (59.1%) were common treatment-related adverse events (AEs); nine (40.9%) patients had Grade 3 or higher AEs. CONCLUSION: IC with trifluridine/tipiracil and oxaliplatin followed by CRT did not improve pCR rate in resectable EGAC compared to pCR from previous reports with CRT alone. We found a correlation between ctDNA clearance and improved survival, which merits further investigation. CLINICAL TRIAL INFORMATION: NCT04097028.	esophagus
Infectious agents and progression from Barrett's oesophagus to oesophageal adenocarcinoma: a nested case-control study.	BACKGROUND: A causal role of high-risk HPV in oesophageal adenocarcinoma development has been hypothesised, but longitudinal evidence is limited. This study aims to investigate a potential causal role of infectious agents in the malignant progression of Barrett's oesophagus. METHODS: Using a retrospective nested case-control study design, index Barrett's biopsies were retrieved for individuals within the Northern Ireland Barrett's oesophagus register who subsequently progressed to oesophageal adenocarcinoma (n = 150) and matched non-progressors (n = 298). Index Barrett's biopsies were assessed for the presence of 142 infectious agents by multiplex polymerase chain reaction using the Luminex platform. RNA in-situ hybridisation assessed persistent transcriptional activity in subsequent tissue samples, for infectious agents detected more frequently in progressors. RESULTS: High-risk HPV genotypes (HPV16 and HPV18) were only identified in the index biopsies of progressors but not non-progressors (4% [5/150] versus 0% [0/298], P = 0.004), though no signs of persistence or transcriptional activity were observed in subsequent tissue. Prevalence of infections did not differ between progressors and non-progressors for any other infectious agents, including Helicobacter Pylori and Herpes. CONCLUSION: Despite a higher prevalence of high-risk HPV in progressors than non-progressors, no evidence of transcriptionally active high-risk HPV was observed in subsequent samples, indicating presence in Barrett's is likely non-causal.	esophagus
Assessment of the participation rate and effectiveness of upper gastrointestinal cancer screening in China: a multicenter population-based screening study.	This study estimated the participation rate and effectiveness of endoscopic screening of upper gastrointestinal cancer (UGIC) in China.From 2014 to 2015, we recruited 192805 adults from seven cities in China to build a prospective cohort for UGIC screening, including esophageal cancer and gastric cancer. Overall, 39991 participants were at high risk for UGIC according to an established risk score system and were recommended for endoscopic examination. Participation rates were reported, and their associated factors were explored. After inverse probability of treatment weighting (IPTW) based on propensity scores, Poisson regression was used to estimate the incidence rate ratio (IRR) and 95%CI for UGIC incidence and mortality between screened and non-screened groups from cohort entry until 31 December 2021.10442 participants underwent endoscopy, giving a participation rate of 26.1%. Higher participation was observed among individuals with higher education levels, history of upper gastrointestinal diseases, and family history of cancer. After a median follow-up of 6.8 years (interquartile range 6.7-6.9), UGIC incidences after IPTW were 94.6 per 100000 person-years in the screened group and 84.7 per 100000 person-years in the non-screened group. The weighted UGIC mortality rates were 13.1 and 33.4 per 100 000 person-years, respectively. The screened group had significantly lower UGIC mortality than the non-screened group, with a weighted IRR of 0.39 (95%CI 0.19-0.82).Participation in endoscopic screening among a high-risk UGIC population in China was low. We found that one-time endoscopic screening significantly reduced mortality caused by UGIC.	esophagus
GRHL3 specifically initiated by the TP63 transcription factor promotes the metastasis of squamous cell carcinogenesis.	Metastasis is the primary cause of death in squamous cell carcinoma (SCC) patients; thus, identification of highly sensitive tumor biomarkers and therapeutic targets that can be exploited to prevent SCC metastasis and clarification of the underlying molecular mechanism is critically important. Reports have shown that Grainyhead-like 3 (GRHL3) plays a crucial role in tumorigenesis and cancer progression; nevertheless, its functions and molecular mechanism in the development of cancer remain controversial. In the present study, GRHL3 was found to be specifically overexpressed in SCCs, including lung squamous cell carcinoma (LUSC), esophageal squamous cell carcinoma (ESCC), and cervical squamous cell carcinoma (CSCC). In particular, the study revealed that high GRHL3 expression is correlated with poor overall survival (OS) and progression-free survival (PFS) in LUSC patients. Functionally, GRHL3 knockdown suppressed the invasion and migration of SCC cells in vitro and decreased their lung metastasis potential in vivo but had little effect on cell proliferation. Mechanistically, the specific overexpression of GRHL3 in SCCs is orchestrated by a well-known oncogenic transcription factor: tumor protein p63 (TP63). GRHL3 stimulates the expression of heparanase (HPSE), thereby activating the AKT-SRC signaling axis. Taken together, our work reveals a novel molecular pathway through which GRHL3 mediates the metastasis of SCCs, which has important implications for the diagnosis and targeted treatment of SCC.	esophagus
Impact of Anastomotic Leaks on Long-Term Survival in Patients with Esophageal Squamous Cell Carcinoma Following McKeown Esophagectomy: A Propensity Score-Matched Analysis.	BACKGROUND: The impact of anastomotic leak (AL) on the long-term survival of patients with esophageal squamous cell carcinoma (ESCC) remains unclear. This study investigated whether AL influences the long-term survival of patients with ESCC following McKeown esophagectomy. PATIENTS AND METHODS: An original database was queried to identify patients with ESCC who underwent McKeown esophagectomy between 2012 and 2020 at a high-volume cancer center. Overall survival (OS) and disease-free survival (DFS) were compared using Kaplan-Meier (KM) curves. Cox regression analysis was used for multivariate analysis. Propensity score matching (PSM) was used to adjust for the confounding factors. RESULTS: A total of 1614 patients were included, of whom 16.9% developed AL. In patients without neoadjuvant therapy, for patients with and without AL, the 5-year OS was 55.8% and 62.0%, and the 5-year DFS was 48.7% and 59.1%, respectively (OS: p = 0.37, DFS: p = 0.046). In the neoadjuvant cohort, for patients with and without AL, the 5-year OS was 57.9% and 63.2%, and the 5-year DFS was 55.4% and 58.8%, respectively (OS: p = 0.48, DFS: p = 0.78). Moreover, AL significantly increased the risk of distant recurrence in patients without neoadjuvant therapy (p = 0.023). CONCLUSIONS: These findings suggest that AL negatively influences DFS in patients without neoadjuvant therapy, but does not significantly affect long-term survival in patients receiving neoadjuvant treatment. Intensive treatment and follow-up plan should be considered when patients without neoadjuvant therapy.	esophagus
PET/MRI is superior to PET/CT in detecting oesophago and gastric carcinomas: a meta-analysis.	OBJECTIVES: To compare the accuracy rates of the detection and staging of oesophago and gastric carcinomas between PET/MRI and PET/CT. METHODS: An extensive librarian-led literature search of PubMed, Embase, Web of Science, the Cochrane Central Library, and CNKI was performed and a meta-analysis was done. RESULTS: Six studies, including 123 participants, were analyzed. PET/MRI had a comparatively high sensitivity in primary lesion detection compared with PET/CT. (RR = 1.14, 95% CI 1.01-1.29, P = 0.036).PET/MRI had no significant statistical differences in all aspects of TNM staging compared with PET/CT. CONCLUSIONS: This systematic review confirmed the advantage of PET/MRI in detecting oesophago and gastric carcinomas.Compared with PET/CT, it can reduce unnecessary radiation exposure and can be used in relevant patients without contraindications of MRI.	esophagus
Neoadjuvant immunochemotherapy for resectable esophageal cancer: A study on efficacy and safety.	The combination of immunosuppressants and chemotherapy has reshaped the treatment landscape for esophageal cancer (EC). This study aimed to evaluate the effectiveness and safety of a neoadjuvant immunochemotherapy (nICT) regimen in patients with resectable EC. A total of 99 eligible patients were included. Data on patient characteristics, nICT regimens, surgical approaches, postoperative outcomes, adverse events (AEs) related to neoadjuvant therapy and surgery, overall survival (OS), and disease-free survival (DFS) were collected. OS, DFS, and safety were the primary endpoints. Cox regression analysis was used to identify prognostic factors in the overall population. Additionally, exploratory research was conducted to assess the clinical value of blood immune indicators in predicting tumor regression. Following surgery, 99.0% of patients achieved complete resection (R0). After neoadjuvant therapy, the number of patients with stage T0N0 increased, with complete or moderate responses being the most common outcomes according to American Joint Committee on Cancer (AJCC)/ College of American Pathologists (CAP)-tumor regression grading (TRG) evaluations (64.7%). The one-year OS and DFS rates were 91.6% and 49.3%, respectively. Grade ≥3 AEs related to neoadjuvant therapy occurred in 21.2% of patients, with gastrointestinal reactions being the most frequent (16 cases, 16.2%). No treatment-related deaths were reported. Grade ≥3 surgery-related AEs occurred in 10.1% of patients, with anastomotic leakage being the most common (six cases, 6.1%). Several factors were associated with significantly improved OS, including chemotherapy regimens combining paclitaxel with platinum, surgical approaches using laparoscopy or thoracotomy (left or right), an interval of ≤34 days between the last treatment and surgery, and the absence of positive lymph node detection. Higher cT staging was significantly associated with worse DFS. Blood immune markers, such as the neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) were found to predict tumor regression in EC patients. In summary, nICT demonstrated favorable effectiveness and safety in resectable EC. The choice of platinum-based chemotherapy agents, rather than the type of immunosuppressant, was associated with prognosis. Moreover, a shorter interval (≤34 days) between the final nICT administration and surgery was linked to improved outcomes.	esophagus
Full RAMIE vs Hybrid RAMIE: a retrospective study on outcomes evaluation and cost considerations.	To compare the results of Minimally Invasive Esophagectomy performed with a Fully Robot-Assisted technique (F-RAMIE) and a Hybrid approach with laparoscopic abdominal phase (H-RAMIE). Multicentric retrospective analysis of patients who underwent F-RAMIE and H-RAMIE between 2018 and 2023. The primary endpoint was the rate of postoperative complications, secondary endpoints were clinical outcomes, oncological results and costs. Survival analyses were calculated according to the Kaplan-Meier method. The economic evaluation included costs related to operating room time, length of stay, surgical tools, and robotic system maintenance. A total of 100 patients from two experienced surgical centers were included: 64 H-RAMIE and 36 F-RAMIE. The two groups were comparable in baseline clinical conditions and staging. F-RAMIE was associated with longer operative time (434.7 ± 46.4 Vs. 477.3 ± 47.5 min, p < 0.001) and shorter length of Intensive Care Unit stay (1.1 ± 1.1 Vs. 2.3 ± 2.3 days, p = 0.002) than H-RAMIE. There were no significant differences in conversion rate, postoperative complications and length of stay. F-RAMIE demonstrated superior lymph node retrieval (43.8 ± 15.2 Vs. 22.4 ± 10.3, p < 0.001), but no differences in R0 resection rates. Overall survival and recurrences were comparable. Cost analysis revealed a slight economic advantage for F-RAMIE (20,556.3 ± 3,601.2 € Vs. 23,302.4 ± 5,894.5 € p = 0.012), mainly due to hospital stay-related cost (11,267.6 ± 5,912.8 € for H-RAMIE Vs. 8,360.3 ± 3,550.6 €, p = 0.007). F-RAMIE and H-RAMIE proved to be equally safe and effective in terms of postoperative complications and oncological outcomes.	esophagus
ROBO1 enhanced esophageal carcinoma cell radioresistance through accelerating G3BP2-mediated eIF3A degradation.	Radiotherapy, as a vital means of esophageal cancer treatment, has benefited countless cancer patients, but owing to the occurrence of radio-resistance, its therapeutic efficiency has been dramatically mitigated. Discovering key biomarkers governing radio-tolerance in esophageal cancer and revealing their inherent molecular mechanisms will be of great significance for clinical cancer treatment. Here, we have found roundabout guidance receptor 1 (ROBO1) was significantly upregulated in esophageal cancerous tissues and showed enhanced expression with the development of cancer staging. Cellular experiments demonstrated ROBO1 directly interacted with eukaryotic translation initiation factor 3A (eIF3A) and accelerated its degradation in esophageal cancer cells after irradiation treatment. Mass spectrum analysis further revealed that in response to irradiation, ROBO1, eIF3A and G3BP2 (Ras GTPase-activating protein-binding protein 2) formed a hetero-complex and triggered lysosomes-mediated protein degradation. Knocking down of G3BP2 abrogated the influence of ROBO1 on eIF3A instability. Besides, ROBO1-mediated eIF3A degradation interrupted P53 translation process which in turn provoked downstream mTOR signaling and increased DNA repair associated genes expressions, resulting in radio-resistance enhancement in cancer cells. In conclusion, our findings revealed a novel role of eIF3A in modulating P53/mTOR signaling activity and provided a drug candidate (ROBO1) for overcoming radio-resistance in esophageal cancer.	esophagus