crossing96/oncoscreening huggingface dataset:
Development and validation of esophageal cancer prediction model based on DeepSurv model: A cohort study.	ObjectiveToday, several new machine learning models are being applied to perform survival analyses; however, due to the variations of the size and characteristics of samples, predictive performance of many models is not ideal. In this work, relevant data were collected from the surveillance, epidemiology, and end results (SEER) database of esophageal cancer patients and a multivariate survival analysis model was established based on DeepSurv model to predict the survival rate of esophageal cancer patients and provide reasonable recommendations for individual treatment of these patients. The application of novel machine learning models in survival analysis has been gaining momentum; however, due to the heterogeneity in sample size and characteristics, the predictive accuracy of many models remains suboptimal. The aim was to forecast the survival rates of esophageal cancer patients and to offer informed recommendations for personalized treatment strategies.MethodsIn this retrospective cohort study, the data of 5276 patients were collected from the SEER database using SEER*Stat software(version 8.4.3). The collected data was divided into training and testing sets with 7:3 ratio and the predictive performance of the model was explored using the concordance index (CI). The efficiencies of different treatment methods were compared. In this study, we developed a survival analysis model based on the DeepSurv model. The data was stratified into training (70%, n = 3693) and testing (30%, n = 1583) sets with a 7:3 ratio. The model's predictive efficacy was assessed using the CI, and the effectiveness of various treatment modalities was comparatively analyzed.ResultsThe selected 5276 patients with esophageal cancer were divided into a training set (70%, 3693) and a testing set (30%, 1583). Cox univariate regression analysis results showed that race, diagnosis year, and marital status were risk factors affecting prognosis (p < 0.05). The consistency indexes of training and test sets were 0.84 and 0.83, respectively. These tests indicated that the model had good performance. There is a significant difference in the therapeutic efficacy between the surgical group and the non-surgical group (p < 0.001).ConclusionsAccording to DeepSurv model, a survival prediction model was developed for patients with esophageal cancer and reasonable suggestions were provided for individual treatment selection. Utilizing the DeepSurv model, we have developed a predictive survival model tailored for esophageal cancer patients, providing actionable insights for the selection of individualized treatment approaches.	esophagus
Preoperative pembrolizumab (anti-PD-1 antibody) combined with chemoradiotherapy for esophageal squamous cell carcinoma: a phase 1/2 trial (PALACE-2).	The role of preoperative anti-PD-1 antibody (pembrolizumab) plus chemoradiotherapy (PPCT) in locally advanced, resectable esophageal squamous cell carcinoma (ESCC) is still unclear. We aimed to investigate the therapeutic effect and safety of PPCT followed by surgery in this study (NCT03792347, NCT04435197). Patients with histologically confirmed, locally advanced, and surgically resectable ESCC were enrolled. They received PPCT with paclitaxel/carboplatin or nab-paclitaxel/carboplatin, followed by esophagectomy 4-6 weeks after treatment. The primary endpoint was the pathologic complete response (pCR) rate. Tumor specimens, blood samples and subcutaneous tumor mouse models were utilized to explore and validate the dynamic characteristics of the tumor microenvironment (TME) of ESCC after PPCT. Among the 143 patients enrolled, 140 received neoadjuvant treatment, and 125 underwent surgery. The pCR rate reached 43.2% (54/125). During neoadjuvant period, 75.7% (106/140) of patients experienced grade three or higher-grade adverse events. After a median follow-up of 17.4 months, patients showed a one-year disease-free survival rate of 91.1%, and an overall survival rate of 96.5%. Using scRNA-seq and cytokine profiling, we identified high IL-6 levels as a predictor of response to PPCT. In vivo experiment revealed that IL-6 neutralization enhanced the efficacy of immunotherapy by increasing CD4(+) T-cell cytotoxicity. This is the first large-scale, multicenter, phase 1/2 trial reporting the short-term results of PPCT for locally advanced resectable ESCC. Although the short-term efficacy was not superior to that of neoadjuvant chemoradiotherapy, PPCT demonstrated acceptable safety and comparable one-year survival. We also revealed an association between the therapeutic response and the ability of anti-IL-6 blockade to enhance the efficacy of immunotherapy.	esophagus
GPRC5A+ myCAFs promote ESCC progression via TGF-β-induced fibroblast activation and ANXA1-mediated M2 macrophage polarization.	Cancer-associated fibroblasts (CAFs) play a pivotal regulatory role in the immune microenvironment of esophageal squamous cell carcinoma (ESCC), reshaping the tumor microenvironment and promoting disease progression through the secretion of various factors. Utilizing single-cell RNA sequencing (scRNA-seq) on 15 ESCC and 11 normal tissues, we identified a distinct terminally differentiated myofibroblast (myCAF_1) subset that was significantly expanded in tumors and correlated with poor patient prognosis. This subpopulation was specifically marked by GPRC5A, a gene we validated as a myCAF_1-specific marker through bulk transcriptomic deconvolution of large cohorts. Functional studies revealed that GPRC5A(+) myCAFs drive ESCC progression via a dual mechanism: (1) Activating the TGF-β/SMAD2/3 pathway to promote the transformation of normal fibroblasts (NFs) into CAFs, and (2) Secreting ANXA1 to recruit monocytes and polarize them into M2-type tumor-associated macrophages (TAMs), thereby fostering an immunosuppressive microenvironment. These findings were confirmed using primary CAFs and NFs models. Our study unveils GPRC5A as a key mediator in ESCC and proposes the GPRC5A/TGF-β/ANXA1 axis as a promising therapeutic target for ESCC treatment.	esophagus
PSD3 as a context-dependent modulator of immune landscape and tumor aggressiveness in esophageal squamous cell carcinoma.	In this study, we investigated PSD3, CD274 (PD-L1), and TNFSF18 as potential immune-related biomarkers in esophageal squamous cell carcinoma (ESCC) using integrative transcriptomic and experimental approaches. CD274 and TNFSF18 were consistently up-regulated in ESCC across both TCGA and GEO datasets, while PSD3 showed significantly higher expression in TCGA but no significant difference in the GEO cohort. Only PSD3 demonstrated a significant association with overall survival, with higher expression correlating with improved prognosis. Interestingly, despite its favorable prognostic value, PSD3 functionally promoted ESCC cell proliferation, invasion, and migration in vitro, while inversely regulating PD-L1 expression. Conversely, heterozygous knockout of PD-L1 in KYSE150 cells impaired tumor aggressiveness. Co-immunoprecipitation revealed a direct physical interaction between PSD3 and PD-L1, suggesting a regulatory axis with implications for immune evasion. These findings position PSD3 as a context-dependent immuno-oncogenic factor and a potential therapeutic target in ESCC.	esophagus
PSAT1 knockdown mediated VDAC1 oligomerization promotes ferroptosis and suppresses cell proliferation in esophageal squamous cell carcinoma.	Phosphoserine aminotransferase 1 (PSAT1) has been widely implicated in the progression of various cancers. However, its functions and underlying mechanisms in esophageal squamous cell carcinoma (ESCC) remain poorly understood. Here, we found that PSAT1 was significantly upregulated in ESCC tissues and cell lines, and its expression was correlated with tumor grade and histological features of esophageal carcinoma (ESCA). Functionally, PSAT1 knockdown markedly suppressed cell proliferation, migration, invasion, and xenograft tumor growth, while promoting ferroptosis in ESCC cells. Conversely, PSAT1 overexpression exerted opposing effects. Mechanistically, PSAT1 interacted with voltage-dependent anion channel 1 (VDAC1) in the cytoplasm of ESCC cells by molecular docking and Co-immunoprecipitation (Co-IP) and facilitated its degradation via the ubiquitin-proteasome pathway. Depletion of PSAT1 increased VDAC1 protein level and induced its oligomerization, leading to mitochondrial membrane potential (MMP) depolarization, cytosolic Ca(2+) accumulation, and mitochondrial permeability transition pore (MPTP) opening, ultimately resulting in mitochondrial dysfunction and ferroptosis. Notably, pharmacological inhibition of VDAC1 by VBIT-12 abrogated PSAT1 silencing-induced ferroptosis, confirming VDAC1 as a critical downstream mediator of PSAT1. In conclusion, our findings establish PSAT1 as a critical metabolic regulator that promotes ESCC progression by suppressing VDAC1-dependent ferroptosis. Therefore, targeting the PSAT1-VDAC1 axis may offer a novel therapeutic approach for ESCC.	esophagus
Targeting FTL regulates ferroptosis and remodels lymph node metastasis microenvironment in esophageal squamous cell carcinoma.	More than half of Esophageal squamous cell carcinoma (ESCC) patients are at an advanced stage when first diagnosed, thus they do not benefit much from radical surgery. Single-cell RNA sequencing (scRNA-seq) data from patients with ESCC lymph node metastasis in our laboratory implied that ferroptosis might play an important role in ESCC metastasis. Ferroptosis was found to be a shared specific pathway between ESCC and adjacent non-tumor tissue, as well as between ESCC lymph node metastasis and adjacent non-tumor tissue, of which FTL was selected as the pivotal target gene within this common pathway. Bioinformatic analyses showed that FTL was highly expressed in both primary and metastatic sites than normal, and patients with high expression had poor prognosis, and its function was related to macrophages in TME. Functional studies have shown that FTL promoted tumor growth, tolerated oxidative stress, reduced the sensitivity of ESCC cells to ferroptosis, facilitated epithelial-mesenchymal transition (EMT) and recruited more macrophages to promote metastasis. Mechanism studies have shown that FTL promotes ESCC development and metastasis via NRF2 pathway and inhibits ferroptosis via NCOA4 protein. In vivo treatment, Brusatol, was found to inhibit FTL expression and have a significant inhibitory effect on ESCC growth and metastasis.	esophagus
The Interplay Between Esophageal Adenocarcinoma and Its Tumor Microenvironment: Toward Innovative Therapies.	Esophageal cancer (EC) is a highly aggressive gastrointestinal malignancy, with a notable increase in incidence over recent decades, representing a significant global health burden. The main histological subtypes are esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), with the former being closely associated with gastroesophageal reflux disease, Barrett's esophagus, and obesity, and its incidence continues to increase in Western populations. The rising incidence of EC, combined with poor survival rates, underscores the need for new therapeutic approaches. A deeper understanding of the molecular basis of this prevalent malignancy may open new avenues for optimal therapeutic strategies, with immunotherapy now central in several clinical trials. Understanding the interplay between the tumor microenvironment (TME) and disease progression is pivotal for managing this malignancy, which remains highly challenging. This review highlights the role of the TME in EAC progression and drug resistance, and recent therapeutic advances.	esophagus
A Novel Approach for Cisplatin-Resistant Esophageal Squamous Cell Carcinoma via Amino Acid Transporter LAT1 Inhibition.	BACKGROUND: Esophageal squamous cell carcinoma (ESCC) represents an aggressive cancer type associated with poor prognosis, often treated with neoadjuvant chemotherapy (NAC) using cisplatin-based regimens. However, cisplatin resistance limits therapeutic efficacy, necessitating a deeper understanding of resistance mechanisms. L-type amino acid transporter 1 (LAT1) plays a crucial role in amino acid uptake and is linked to cancer cell survival through activation of the mammalian target of rapamycin (mTOR) pathway. The involvement of LAT1 in cisplatin resistance in ESCC remains unclear. METHODS: LAT1 expression in ESCC patient samples post-NAC was evaluated by immunohistochemistry, and its association with clinicopathological factors and survival outcomes was analyzed. ESCC cell lines with varying cisplatin sensitivities were assessed for LAT1 expression using western blotting. Amino acid metabolism was examined via radiotracer uptake of (18)F-FET and (18)F-FDG. RNA sequencing was conducted to identify differentially expressed genes associated with mTOR signaling and autophagy. Finally, the effect of the LAT1 inhibitor JPH203 on cell proliferation was tested. RESULTS: High LAT1 expression was significantly associated with larger tumor size, lymph node metastasis, advanced pathological stage, and poor NAC response. Patients with high LAT1 expression exhibited shorter disease-free survival and overall survival. Cisplatin-resistant ESCC cells (KYSE520) showed elevated LAT1 expression, which further increased following cisplatin treatment. Radiotracer assays revealed that (18)F-FET uptake was significantly higher in KYSE520 after cisplatin treatment compared to the sensitive cell line TE5. RNA sequencing identified regulation of mTOR pathway components and autophagy-related genes in cisplatin-resistant cells. Treatment with JPH203 significantly suppressed cell proliferation, particularly in KYSE520 cells, indicating LAT1's role in sustaining tumor cell survival under chemotherapy stress. CONCLUSION: LAT1 contributes to cisplatin resistance in ESCC by sustaining amino acid metabolism and promoting mTOR-dependent autophagy. Targeting LAT1 with JPH203 enhances cisplatin sensitivity, suggesting that LAT1 inhibition could be a promising therapeutic strategy for overcoming chemoresistance in ESCC.	esophagus
AGA Clinical Practice Guideline on Surveillance of Barrett's Esophagus.	BACKGROUND & AIMS: Barrett's esophagus (BE) is the only identifiable precursor to esophageal adenocarcinoma (EAC). Endoscopic surveillance has been proposed for early detection of BE-related neoplasia and reducing EAC mortality. This clinical practice guideline aims to inform clinicians and patients by providing evidence-based practice recommendations for surveillance in patients with BE. METHODS: The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and make recommendations. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients, conducted an evidence review, and used the Evidence-to-Decision Framework to develop recommendations regarding the role of endoscopic surveillance in patients with BE. The clinical domains addressed included: (1) overall role of endoscopic surveillance, (2) surveillance in patients with columnar-lined esophagus <1 cm, (3) optimal imaging modalities, (4) adjunctive sampling techniques, (5) the utility of biomarkers in risk-stratification, (6) chemopreventive strategies, and (7) antireflux procedures in the prevention of progression in patients with BE. Clinical recommendations were based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 8 recommendations. Based on the available evidence, the panel provided a conditional recommendation in favor of surveillance for patients with nondysplastic BE. In patients with columnar-lined esophagus <1 cm, a conditional recommendation was made against endoscopic surveillance. The panel made a strong recommendation in favor of a combination of high-definition white light endoscopy and chromoendoscopy compared with white light endoscopy alone. The panel made no recommendation on the use of enhanced sampling techniques, such as wide-area transepithelial sampling to enhance neoplasia detection and biomarkers such as p53 and TissueCypher to predict progression in BE. The panel provided a conditional recommendation for the use of daily proton pump inhibitor therapy compared with no therapy and compared with antireflux surgery to prevent progression in BE. CONCLUSIONS: This document provides a comprehensive outline on the role of surveillance in patients with BE. Key implementation statements included in this document stress the importance of a high-quality endoscopy examination, sampling using a structured biopsy protocol, and confirming the diagnosis of BE-related neoplasia by an expert pathologist. This document also provides guidance on surveillance intervals and management of patients with BE-related low-grade dysplasia and indefinite for dysplasia. Providers should engage in shared decision making based on patient preferences. Limitations and gaps in the evidence are highlighted to guide future research opportunities. GUIDELINE ENDORSEMENT: This guideline is endorsed by the Canadian Association of Gastroenterology.	esophagus
Chemoradiotherapy Versus Radiotherapy in Patients With Stage T1N0M0 Esophageal Cancer: A Retrospective Cohort Study.	BACKGROUND AND AIM: The aim of this study is to compare the survival outcomes between radiotherapy and chemoradiotherapy in patients with stage T1N0M0 esophageal cancer. METHODS: Stage T1N0M0 esophageal cancer patients treated with either radiotherapy or chemoradiotherapy were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2020. Cancer-specific survival (CSS) and overall survival (OS) were compared between the radiotherapy and chemoradiotherapy groups. RESULTS: A total of 41 patients (22.9%) underwent radiotherapy, while 138 patients (77.1%) received chemoradiotherapy. For stage T1a cases, chemoradiotherapy exhibited a similar 5-year CSS (35.9% vs. 26.1%; hazard ratio [HR] = 0.84, 95% confidence interval [CI]: 0.49-1.42; p = 0.511) and OS (24.1% vs. 10.0%; HR = 0.77, 95% CI: 0.50-1.20; p = 0.249) compared to radiotherapy. For stage T1b cases, chemoradiotherapy exhibited a similar 5-year CSS (33.4% vs. 18.2%; HR = 1.05, 95% CI: 0.41-2.70; p = 0.919) and OS (23.4% vs. 9.1%; HR = 0.68, 95% CI: 0.34-1.36; p = 0.272) compared to radiotherapy. Multivariable proportional hazards regression analysis confirmed that chemoradiotherapy was not an independent prognostic factor for CSS (HR = 0.89, 95% CI: 0.29-2.74; p = 0.833). However, chemoradiotherapy was an independent prognostic factor for OS (HR = 0.42, 95% CI: 0.19-0.94; p = 0.034). CONCLUSION: Radiotherapy is comparable to chemoradiotherapy in stage T1a cases. However, chemoradiotherapy is superior to radiotherapy in stage T1b patients.	esophagus
m6A reader IGF2BP2 mediates paclitaxel resistance in esophageal squamous cell carcinoma via FOXM1 mRNA stabilization.	Esophageal squamous cell carcinoma (ESCC) ranks among the primary contributors to cancer‑related mortality in China. Resistance to paclitaxel markedly diminishes its therapeutic effectiveness and outcomes. Anaerobic glycolysis is a pivotal mechanism in cancer progression. Insulin‑like growth factor 2 mRNA binding protein 2 (IGF2BP2) as a reader of RNA N6‑methyladenosine (m6A) modification ensures the stability of RNA at the post‑transcriptional level. Nonetheless, the role and mechanism of IGF2BP2 in mediating paclitaxel resistance and anaerobic glycolysis in ESCC remain unclear. The current study selected two ESCC cell lines (KYSE30 and KYSE150). Cell proliferation and clonogenic ability were assessed via functional experiments. Apoptosis was quantified through flow cytometry. The rate of anaerobic glycolysis was determined via glycolysis assays. The stability of Forkhead box M1 (FOXM1) mRNA was assessed through reverse transcription‑quantitative polymerase chain reaction following actinomycin D treatment. Protein levels were analyzed through western blotting. Bioinformatics analysis revealed an overexpression of IGF2BP2 in ESCC. Furthermore, IGF2BP2 silencing inhibited cell proliferation and clonogenic activity. RNA and m6A‑sequencing results suggested that FOXM1 is critical to IGF2BP2‑mediated paclitaxel resistance in ESCC. Additionally, it was discovered that the silencing of IGF2BP2 compromises FOXM1 mRNA stability, reduces anaerobic glycolysis, and diminishes paclitaxel resistance. Finally, FOXM1 overexpression mitigated the effects of IGF2BP2 silencing in ESCC cells. The current findings underscore the significant role of the IGF2BP2‑FOXM1 signaling pathway in modulating anaerobic glycolysis and paclitaxel resistance in ESCC, offering insights into future therapeutic approaches to this malignancy.	esophagus
Discovery of LD-110 as an Effective LSD1 PROTAC Degrader for the Treatment of Esophagus Squamous Cancer.	LSD1, a pivotal epigenetic regulator mediating histone demethylation, is an attractive therapeutic target due to its oncogenic roles in cancers. Although numerous small-molecule inhibitors of LSD1 were advanced to clinical trials, only one PROTAC-based degrader was reported most recently. Here, we report a potent and efficacious proteolysis-targeting chimera (PROTAC) degrader, LSD1, designated as LD-110. Biochemically, LD-110 promotes LSD1 degradation and increases the level of H3K4 dimethylation in a ubiquitin-proteasome-dependent manner. Biologically, LD-110 inhibits the growth and survival of multiple esophagus squamous cancer cell (ESCC) lines by inducing apoptosis with much greater effectiveness than its small-molecule warhead LI-1. Finally, LD-110 effectively suppresses tumor growth in a KYSE-150 xenograft tumor model without obvious signs of toxicity, while LI-1 is largely ineffective. Collectively, LD-110 is a promising therapeutic candidate for PROTAC-based targeted therapy of ESCC through LSD1 degradation and can also be used as a versatile tool for probing LSD1 biology.	esophagus
Pembrolizumab plus chemotherapy versus chemotherapy for advanced esophageal cancer: 5-year extended follow-up for the randomized phase III KEYNOTE-590 study.	BACKGROUND: The global KEYNOTE-590 trial was the first to show a significant improvement in survival with immunotherapy plus chemotherapy in the first-line treatment of esophageal cancer (EC) and supported the approval of pembrolizumab plus chemotherapy in this setting. After a median follow-up of 22.6 months, pembrolizumab plus chemotherapy compared with placebo plus chemotherapy had a manageable safety profile and significantly improved survival of participants with previously untreated advanced EC. Results of a median follow-up of 58.8 months (range 49.2-70.6 months) are reported. PATIENTS AND METHODS: Adults with previously untreated advanced EC or Siewert type 1 gastroesophageal junction cancer were randomly assigned 1 : 1 to receive chemotherapy with or without pembrolizumab. Study outcomes were efficacy and safety. RESULTS: Overall, 749 participants received pembrolizumab plus chemotherapy (n = 373) or placebo plus chemotherapy (n = 376). Median overall survival was 12.3 months versus 9.8 months [hazard ratio (HR) 0.72, 95% confidence interval (CI) 0.62-0.84] with pembrolizumab plus chemotherapy versus placebo plus chemotherapy; 5-year survival rates were 10.6% and 3.0%. Median progression-free survival (PFS) was 6.3 months versus 5.8 months (HR 0.64, 95% CI 0.54-0.75); 5-year PFS rates were 5.5% and not reached. Grade ≥3 treatment-related adverse events occurred in 71.9% and 67.6% of participants in the pembrolizumab plus chemotherapy and placebo plus chemotherapy groups, respectively. CONCLUSION: Data from KEYNOTE-590 continue to show durable efficacy after 5 years, and pembrolizumab plus chemotherapy more than tripled the 5-year overall survival rate compared with placebo plus chemotherapy, with no new safety signals. These results support first-line therapy with pembrolizumab plus chemotherapy as standard for previously untreated patients with advanced EC with programmed death-ligand 1 combined positive score ≥1.	esophagus