crossing96/oncoscreening huggingface dataset:
Clinical Outcome-Related Cancer Pathways and Mutational Signatures in Patients With Unresectable Esophageal Squamous Cell Carcinoma Treated With Chemoradiotherapy.	PURPOSE: Definitive chemoradiotherapy (dCRT) is a standard-of-care for locally advanced unresectable esophageal squamous cell carcinoma (ESCC). However, even in individuals treated with the same dCRT regimen, differences in the local control rate and radiation-induced thoracic toxicity exist (radiation-induced esophagitis [RIE]). METHODS AND MATERIALS: Here, we describe a comprehensive genomic evaluation of pretreatment tumor tissue samples from 183 patients with ESCC using targeted sequencing of 474 cancer-related genes. The association between endpoints (progression-free survival [PFS], overall survival, locoregional relapse-free survival, distant metastasis-free survival), toxicity (RIE) and genomic features, including altered pathways and the mutational signature, was analyzed. An independent cohort of 84 stage II-III patients with ESCC was used for validation. RESULTS: Gene alterations in the cell cycle pathway were identified in 87% of cases. Other frequently altered pathways included PI3K-AKT (45.9%), NOTCH (38.3%), NRF2 (36.6%), RKT-RAS (28.4%), and homologous recombination repair (HRR; 20.2%). HRR pathway alterations correlated with shortened PFS (mutation vs wild-type: 9.00 vs 14.40 months, hazard ratio, 2.10; 95% confidence interval, 1.29-3.44), while altered RTK-RAS pathways were correlated with worse overall survival in patients with ESCC treated with chemoradiotherapy (mutation vs wild-type: 23.70 vs 33.50 months; hazard ratio, 1.65; 95% confidence interval, 1.01-2.69). Furthermore, enrichment of apolipoprotein B mRNA editing enzyme, catalytic polypeptide (APOBEC) signatures (signatures 2 and 13) was identified in ESCC tumors with altered HRR pathways. High APOBEC signatures and an altered HRR pathway were correlated with poor prognoses in dCRT-treated ESCC. Moreover, the APOBEC signature and/or the presence of HRR pathway alterations were associated with poor PFS and overall survival, which was validated in an independent whole exome sequence cohort. Notably, the altered HRR pathway was also associated with high-grade RIE toxicity in patients with ESCC. CONCLUSIONS: Collectively, our results support the use of comprehensive genomic profiling to guide treatment and minimize RIE in patients with ESCC.	esophagus
Automated clinical decision support system with deep learning dose prediction and NTCP models to evaluate treatment complications in patients with esophageal cancer.	BACKGROUND AND PURPOSE: This study aims to investigate how accurate our deep learning (DL) dose prediction models for intensity modulated radiotherapy (IMRT) and pencil beam scanning (PBS) treatments, when chained with normal tissue complication probability (NTCP) models, are at identifying esophageal cancer patients who are at high risk of toxicity and should be switched to proton therapy (PT). MATERIALS AND METHODS: Two U-Net were created, for photon (XT) and proton (PT) plans, respectively. To estimate the dose distribution for each patient, they were trained on a database of 40 uniformly planned patients using cross validation and a circulating test set. These models were combined with a NTCP model for postoperative pulmonary complications. The NTCP model used the mean lung dose, age, histology type, and body mass index as predicting variables. The treatment choice is then done by using a ΔNTCP threshold between XT and PT plans. Patients with ΔNTCP ≥ 10% were referred to PT. RESULTS: Our DL models succeed in predicting dose distributions with a mean error on the mean dose to the lungs (MLD) of 1.14 ± 0.93% for XT and 0.66 ± 0.48% for PT. The complete automated workflow (DL chained with NTCP) achieved 100% accuracy in patient referral. The average residual (ΔNTCP ground truth - ΔNTCP predicted) is 1.43 ± 1.49%. CONCLUSION: This study evaluates our DL dose prediction models in a broader patient referral context and demonstrates their ability to support clinical decisions.	esophagus
Integrating (18) F-FDG PET/CT with lung dose-volume for assessing lung inflammatory changes after arc-based radiotherapy for esophageal cancer: A pilot study.	OBJECTIVE: The incidence of radiation pneumonitis (RP) has a highly linear relationship with low-dose lung volume. We previously established a volume-based algorithm (VBA) method to improve low-dose lung volume in radiotherapy (RT). This study assessed lung inflammatory changes by integrating fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18) F-FDG PET/CT) with VBA for esophageal cancer patients undergoing arc-based RT. METHODS: Thirty esophageal cancer patients received (18) F-FDG PET/CT imaging pre-RT and post-RT were included in a retrospective pilot study. We fused lung doses and parameters of PET/CT in RT planning. Based on VBA, we used the 5Gy isodose curve to define high-dose (HD) and low-dose (LD) regions in the lung volume. We divided patients into non-RP (nRP) and RP groups. The maximum, mean standardized uptake value (SUVmax, SUVmean), global lung glycolysis (GLG), mean lung dose (MLD) and V(5-30) in lungs were analyzed. Area under the curve values were utilized to identify optimal cut-off values for RP. RESULTS: Eleven patients in the nRP group and 19 patients in the RP group were identified. In 30 RP lungs, post-RT SUVmax, SUVmean and GLG of HD regions showed significant increases compared to values for pre-RT lungs. There were no significant differences in values of 22 nRP lungs. Post-RT SUVmax and SUVmean of HD regions, MLD, and lung V(5) and V(10) in RP lungs were significantly higher than in nRP lungs. For detecting RP, the optimal cut-off values were post-RT SUVmax > 2.28 and lung V(5) > 47.14%. CONCLUSION: This study successfully integrated (18) F-FDG PET/CT with VBA to assess RP in esophageal cancer patients undergoing RT. Post-RT SUVmax > 2.28 and lung V(5)  > 47.14% might be potential indicators of RP.	esophagus
LncRNA RPL34-AS1 suppresses the proliferation, migration and invasion of esophageal squamous cell carcinoma via targeting miR-575/ACAA2 axis.	BACKGROUND: Long noncoding RNAs (lncRNAs) are abnormally expressed in a broad type of cancers and play significant roles that regulate tumor development and metastasis. However, the pathological roles of lncRNAs in esophageal squamous cell carcinoma (ESCC) remain largely unknown. Here we aimed to investigate the role and regulatory mechanism of the novel lncRNA RPL34-AS1 in the development and progression of ESCC. METHODS: The expression level of RPL34-AS1 in ESCC tissues and cell lines was determined by RT-qPCR. Functional experiments in vitro and in vivo were employed to explore the effects of RPL34-AS1 on tumor growth in ESCC cells. Mechanistically, fluorescence in situ hybridization (FISH), bioinformatics analyses, luciferase reporter assay, RNA immunoprecipitation (RIP) assay and western blot assays were used to detect the regulatory relationship between RPL34-AS1, miR-575 and ACAA2. RESULTS: RPL34-AS1 was significantly down-regulated in ESCC tissues and cells, which was negatively correlated with overall survival in ESCC patients. Functionally, upregulation of RPL34-AS1 dramatically suppressed ESCC cell proliferation, colony formation, invasion and migration in vitro, whereas knockdown of RPL34-AS1 elicited the opposite function. Consistently, overexpression of RPL34-AS1 inhibited tumor growth in vivo. Mechanistically, RPL34-AS1 acted as a competing endogenous RNA (ceRNA) of miR-575 to relieve the repressive effect of miR-575 on its target ACAA2, then suppressed the tumorigenesis of ESCC. CONCLUSIONS: Our results reveal a role for RPL34-AS1 in ESCC tumorigenesis and may provide a strategy for using RPL34-AS1 as a potential biomarker and an effect target for patients with ESCC.	esophagus
Long noncoding RNA CDKN2B-AS1 silencing protects against esophageal cancer cell invasion and migration by inactivating the TFAP2A/FSCN1 axis.	Esophageal cancer (EC) is the most aggressive malignancy in the gastrointestinal tract. Long noncoding RNA cyclin-dependent kinase inhibitor 2 B antisense RNA 1 (CDKN2B-AS1) is implicated in EC development. However, the specific mechanisms involved remain poorly defined. Therefore, this research aimed to explore the mechanism of action of CDKN2B-AS1 in EC. Quantitative real-time polymerase chain reaction was conducted to measure CDKN2B-AS1 expression in EC cells and western blotting was utilized to evaluate transcription factor AP-2 alpha (TFAP2A) and fascin actin-bundling protein 1 (FSCN1) expression. After gain-of-function and loss-of-function assays, cell proliferation, migration, invasion, apoptosis, and apoptosis-related protein expression were assessed using cell counting kit-8, scratch tests, Transwell assays, flow cytometry, and western blotting, respectively. The binding relationship between CDKN2B-AS1 and TFAP2A was assessed by RNA immunoprecipitation and RNA pull-down assays. The binding relationship between TFAP2A and FSCN1 was evaluated using dual-luciferase reporter and chromatin immunoprecipitation assays. Tumor xenografts from nude mice were used for in vivo verification. CDKN2B-AS1, TFAP2A, and FSCN1 were upregulated in EC cells. Mechanistically, CDKN2B-AS1 transcriptionally activated FSCN1 by recruiting TFAP2A to the FSCN1 promoter. Silencing CDKN2B-AS1 or TFAP2A suppressed EC cell proliferative, migrating, and invasive properties and augmented apoptosis. TFAP2A was bound to CDKN2B-AS1 and the FSCN1 promoter. Overexpression of TFAP2A or FSCN1 abolished the effects of CDKN2B-AS1-silencing on EC cell function. CDKN2B-AS1 silencing curtailed tumorigenesis in nude mice, which was nullified by the upregulation of TFAP2A or FSCN1. Our findings demonstrated the antioncogenic effects of silencing CDKN2B-AS1 in EC through inactivation of the TFAP2A/FSCN1 axis.	esophagus
Identification of clinical prognostic features of esophageal cancer based on m6A regulators.	BACKGROUND: Esophageal cancer (ESCA) is a common malignancy with high morbidity and mortality. n6-methyladenosine (m6A) regulators have been widely recognized as one of the major causes of cancer development and progression. However, for ESCA, the role of regulators is unclear. The aim of this study was to investigate the role of m6A RNA methylation regulators in the immune regulation and prognosis of ESCA. METHODS: RNA-seq data were downloaded using the Cancer Genome Atlas (TCGA) database, and the expression differences of m6A RNA methylation regulators in ESCA were analyzed. Further m6A methylation regulator markers were constructed, and prognostic and predictive values were assessed using survival analysis and nomograms. Patients were divided into low-risk and high-risk groups. The signature was evaluated in terms of survival, single nucleotide polymorphism (SNP), copy number variation (CNV), tumor mutation burden (TMB), and functional enrichment analysis (TMB). The m6A expression of key genes in clinical specimens was validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: In ESCA tissues, most of the 23 regulators were significantly differentially expressed. LASSO regression analysis included 7 m6A-related factors (FMR1, RBMX, IGFBP1, IGFBP2, ALKBH5, RBM15B, METTL14). In addition, this study also identified that the risk model is associated with biological functions, including base metabolism, DNA repair, and mismatch repair. In this study, a nomogram was created to predict the prognosis of ESCA patients. Bioinformatics analysis of human ESCA and normal tissues was performed using qRT-PCR. Finally. Seven genetic features were found to be associated with m6A in ESCA patients. The results of this study suggest that three different clusters of m6A modifications are involved in the immune microenvironment of ESCA, providing important clues for clinical diagnosis and treatment.	esophagus
Expanding beyond endoscopy: A review of non-invasive modalities in Barrett's esophagus screening and surveillance.	Barrett's esophagus (BE) is a condition that results from replacement of the damaged normal squamous esophageal mucosa to intestinal columnar mucosa and is the most significant predisposing factor for development of esophageal adenocarcinoma. Current guidelines recommend endoscopic evaluation for screening and surveillance based on various risk factors which has limitations such as invasiveness, availability of a trained specialist, patient logistics and cost. Trans-nasal endoscopy is a less invasive modality but still has similar limitations such as limited availability of trained specialist and costs. Non-endoscopic modalities, in comparison, require minimal intervention, can be done in an office visit and has the potential to be a more ideal choice for mass public screening and surveillance, particularly in patents at low risk for BE. These include newer generations of esophageal capsule endoscopy which provides direct visualization of BE, and tethered capsule endomicroscopy which can obtain high-resolution images of the esophagus. Various cell collection devices coupled with biomarkers have been used for BE screening. Cytosponge, in combination with TFF3, as well as EsophaCap and EsoCheck have shown promising results in various studies when used with various biomarkers. Other modalities including circulatory microRNAs and volatile organic compounds that have demonstrated favorable outcomes. Use of these cell collection methods for BE surveillance is a potential area of future research.	esophagus
N-linked glycoproteomic profiling in esophageal squamous cell carcinoma.	BACKGROUND: Mass spectrometry-based proteomics and glycomics reveal post-translational modifications providing significant biological insights beyond the scope of genomic sequencing. AIM: To characterize the N-linked glycoproteomic profile in esophageal squamous cell carcinoma (ESCC) via two complementary approaches. METHODS: Using tandem multilectin affinity chromatography for enrichment of N-linked glycoproteins, we performed N-linked glycoproteomic profiling in ESCC tissues by two-dimensional gel electrophoresis (2-DE)-based and isobaric tags for relative and absolute quantification (iTRAQ) labeling-based mass spectrometry quantitation in parallel, followed by validation of candidate glycoprotein biomarkers by Western blot. RESULTS: 2-DE-based and iTRAQ labeling-based quantitation identified 24 and 402 differentially expressed N-linked glycoproteins, respectively, with 15 in common, demonstrating the outperformance of iTRAQ labeling-based quantitation over 2-DE and complementarity of these two approaches. Proteomaps showed the distinct compositions of functional categories between proteins and glycoproteins with differential expression associated with ESCC. Western blot analysis validated the up-regulation of total procathepsin D and high-mannose procathepsin D, and the down-regulation of total haptoglobin, high-mannose clusterin, and GlcNAc/sialic acid-containing fraction of 14-3-3ζ in ESCC tissues. The serum levels of glycosylated fractions of clusterin, proline-arginine-rich end leucine-rich repeat protein, and haptoglobin in patients with ESCC were remarkably higher than those in healthy controls. CONCLUSION: Our study provides insights into the aberrant N-linked glycoproteome associated with ESCC, which will be a valuable resource for future investigations.	esophagus
Atom Search Optimization with the Deep Transfer Learning-Driven Esophageal Cancer Classification Model.	Esophageal cancer (EC) is a commonly occurring malignant tumor that significantly affects human health. Earlier recognition and classification of EC or premalignant lesions can result in highly effective targeted intervention. Accurate detection and classification of distinct stages of EC provide effective precision therapy planning and improve the 5-year survival rate. Automated recognition of EC can aid physicians in improving diagnostic performance and accuracy. However, the classification of EC is challenging due to identical endoscopic features, like mucosal erosion, hyperemia, and roughness. The recent developments of deep learning (DL) and computer-aided diagnosis (CAD) models have been useful for designing accurate EC classification models. In this aspect, this study develops an atom search optimization with a deep transfer learning-driven EC classification (ASODTL-ECC) model. The presented ASODTL-ECC model mainly examines the medical images for the existence of EC in a timely and accurate manner. To do so, the presented ASODTL-ECC model employs Gaussian filtering (GF) as a preprocessing stage to enhance image quality. In addition, the deep convolution neural network- (DCNN-) based residual network (ResNet) model is applied as a feature extraction approach. Besides, ASO with an extreme learning machine (ELM) model is utilized for identifying the presence of EC, showing the novelty of the work. The performance of the ASODTL-ECC model is assessed and compared with existing models under several medical images. The experimental results pointed out the improved performance of the ASODTL-ECC model over recent approaches.	esophagus
[The Development of Combinatorial Cancer Immunotherapy with Anti-PD-1 Therapy and Radiotherapy for Patients with Esophageal Squamous Cell Carcinoma].	Despite the remarkable progress in cancer therapy, the 5-year survival rate for esophageal cancer patients who can be treated with surgery is still limited to 59.3%. We have recently treated patients with advanced or recurrent esophageal cancer with anti-PD-1 antibody as a new treatment strategy. However, its response rate was not as high as expected at 19.3%, and the development of new therapeutic strategy to further improve its efficacy is eagerly expected. In this study, we investigated the possibility of combinatorial cancer immunotherapy using anti-PD-1 therapy and local radiotherapy in order to enhance the therapeutic efficacy of anti-PD-1 therapy. As a result, although chemoradiotherapy induced the tumor antigen specific cytotoxic T lymphocytes(CTL)in about 40% of patients with advanced esophageal squamous cell carcinoma (ESCC), PD-L1 expression on ESCC cells was observed in approximately 80% of ESCC patients. This means that induced tumor antigen specific CTL may be immunosuppressed through the PD-1 pathway at the ESCC tumor microenvironment, and the addition of anti-PD-1 therapy could be effective in such a situation. Although further studies are needed, the combinatorial cancer immunotherapy using anti-PD-1 therapy and local radiotherapy is expected to be a promising treatment strategy in patients with ESCC.	esophagus
A rare case of esophageal anthracosis presenting as a submucosal tumor.	A 62-year-old man with a history of heartburn and regurgitation was referred for the management of a black lesion in the middle esophagus. Our Esophagogastroduodenoscopy (EGD) showed a 13 mm, black protruding lesion located 29cm from the incisor teeth. Endoscopic ultrasonography (EUS) showed a 11.7 mm×7.2 mm hyperechoic mass in the esophageal wall arising in layer 2 and 3. Biopsy of the lesion showed a black and elastic hard appearance. Pathological examination showed chronic inflammatory with coal dust underneath the mucosal epithelium.	esophagus
Demystifying the Functional Role of Nuclear Receptors in Esophageal Cancer.	Esophageal cancer (EC), an aggressive and poorly understood disease, is one of the top causes of cancer-related fatalities. GLOBOCAN 2020 reports that there are 544,076 deaths and 604,100 new cases expected worldwide. Even though there are various advancements in treatment procedures, this cancer has been reported as one of the most difficult cancers to cure, and to increase patient survival; treatment targets still need to be established. Nuclear receptors (NRs) are a type of transcription factor, which has a key role in several biological processes such as reproduction, development, cellular differentiation, stress response, immunity, metabolism, lipids, and drugs, and are essential regulators of several diseases, including cancer. Numerous studies have demonstrated the importance of NRs in tumor immunology and proved the well-known roles of multiple NRs in modulating proliferation, differentiation, and apoptosis. There are surplus of studies conducted on NRs and their implications in EC, but only a few studies have demonstrated the diagnostic and prognostic potential of NRs. Therefore, there is still a paucity of the role of NRs and different ways to target them in EC cells to stop them from spreading malignancy. This review emphasizes the significance of NRs in EC by discussing their diverse agonists as well as antagonists and their response to tumor progression. Additionally, we emphasize NRs' potential to serve as a novel therapeutic target and their capacity to treat and prevent EC.	esophagus
Dual Inhibition of EGFR and IGF-1R Signaling Leads to Enhanced Antitumor Efficacy against Esophageal Squamous Cancer.	Both the epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF-1R) have been implicated in the development of cancers, and the increased expression of both receptors has been observed in esophageal cancer. However, the tyrosine kinase inhibitors of both receptors have thus far failed to provide clinical benefits for esophageal cancer patients. Studies have confirmed the complicated crosstalks that exist between the EGFR and IGF-1R pathways. The EGFR and IGF-1R signals act as mutual compensation pathways, thereby conveying resistance to EGFR or IGF-1R inhibitors when used alone. This study evaluated the antitumor efficacy of the EGFR/HER2 inhibitors, gefitinib and lapatinib, in combination with the IGF-1R inhibitor, linsitinib, on the esophageal squamous cell carcinoma (ESCC). Gefitinib or lapatinib, in combination with linsitinib, synergistically inhibited the proliferation, migration, and invasion of ESCC cells, caused significant cell cycle arrest, and induced marked cell apoptosis. Their combination demonstrated stronger inhibition on the activation of EGFR, HER2, and IGF-1R as well as the downstream signaling molecules. In vivo, the addition of linsitinib to gefitinib or lapatinib also potentiated the inhibition effects on the growth of xenografts. Our results suggest the next clinical exploration of the combination of gefitinib or lapatinib with linsitinib in the treatment of ESCC patients.	esophagus
Comparison of Efficacy and Safety of Taxanes Plus Platinum and Fluorouracil Plus Platinum in the First-Line Treatment of Esophageal Cancer: A Systematic Review and Meta-Analysis.	Fluoropyrimidine plus platinum (FP) and taxanes plus platinum (TP) are standard treatments for esophageal cancer (EC). This systematic review and meta-analysis aim to explore the difference in the therapeutic effect and toxicity of FP and TP regimens in EC patients. PubMed, Embase, and Cochrane were fully searched and analyzed to find relevant articles on EC patients treated with FP and TP regimens up to 22 March 2022. Thirty-one studies, with a total of 3432 participants, were included in this review. The primary outcomes showed that the prognosis and therapeutic efficacy of TP groups were better than those of FP groups for the EC patients treated with definitive chemoradiotherapy treatment (3-year OS: RR: 1.25, 95% CI: 1.08−1.44, p = 0.003; 3-year PFS: RR: 1.43, 95% CI: 1.17−1.75, p = 0.0006; ORR: RR: 1.17, 95% CI: 1.06−1.29, p = 0.001). However, TP therapy was significantly correlated with a higher incidence of leukopenia and thrombocytopenia (p < 0.05). In the preoperative neoadjuvant chemoradiotherapy group, these two groups had a similar survival time (p > 0.05). The FP regimen corresponded to a higher incidence of thrombocytopenia, while the TP regimen was associated with an increased incidence of febrile leukopenia (p < 0.05). Therefore, TP regimens could generate both superior clinical response and survival benefits when compared with FP regimens in EC patients undergoing definitive chemoradiotherapy.	esophagus