crossing96/oncoscreening huggingface dataset:
FLOT-regimen Chemotherapy and Transthoracic en bloc Resection for Esophageal and Junctional Adenocarcinoma.	BACKGROUND AND AIMS: The FLOT4-AIO trial established the FLOT regimen as a compelling option for gastric, junctional and esophageal adenocarcinoma. Data on FLOT with en-bloc transthoracic esophagectomy (TTE) are limited. This study explored operative complications, tolerance, toxicity, physiological impact, and oncologic outcomes. STUDY DESIGN: An observational cohort study on consecutive patients at 3 tertiary centers undergoing FLOT and TTE. Toxicity, operative complications (per ECCG definitions), tumor regression grade (TRG), recurrences and survival were documented, as well as pre and post FLOT assessment of sarcopenia and pulmonary physiology. RESULTS: 175 patients (cT2-4a, Nany) commenced treatment, 84% male, median age 65, 94% cT3/T4a, 73% cN+. 89% completed 4 preoperative cycles, and 35% all cycles. Grade 3/4 toxicities included neutropenia (12%), diarrhoea (13%), and infection (15%). Sarcopenia increased from 18% to 37% (P = 0.020), and diffusion capacity (DLCO) decreased by 8% (-34% + 25%; P < 0.010). On pathology, ypT3/4 was 59%, and ypN+54%, with 10% TRG 1, 14% TRG 2, and 76% TRG3-5, and R0 95%. 161 underwent TTE, with an in-hospital mortality of 0.6%, 24%-pneumonia, 11%-anastomotic leak, and Clavien Dindo ≥III in 27%. At a median follow up of 12 months (1-85), 33 relapsed, 8 (5%) locally, and 3yr survival was 60%. CONCLUSION: FLOT and en bloc TTE was safe, with no discernible impact on operative complications, with 24% having a major pathologic response. Caveats include a limited pathologic response in the majority, and negative impact on muscle mass and lung physiology, and low use of adjuvant cycles. These data may provide a real-world benchmark for this complex care pathway.	esophagus
Clinical Significance of Fusobacterium nucleatum Infection and Regulatory T Cell Enrichment in Esophageal Squamous Cell Carcinoma.	A variety of pathogenic microorganisms promote tumor occurrence and development through long-term colonization in the body. Fusobacterium nucleatum (F. nucleatum) is abundant in precancerous esophageal lesions and is closely related to the malignant progression of esophageal squamous cell carcinoma (ESCC). The invasion of exogenous microorganisms can reshape the immune microenvironment, make the immune system incapacitated, and assist tumor cells in immune escape. A variety of pathogenic microorganisms induce the recruitment of regulatory T cell (Tregs) to allow tumor cells to escape immune surveillance and provide favorable conditions for their own long-term colonization. Tregs are one of the major obstacles to tumor immunotherapy and have a significant positive correlation with the occurrence and development of many kinds of tumors. Because F. nucleatum can instantly enter cells and colonize for a long time, we speculated that F. nucleatum infection could facilitate the immune escape of tumor cells through enrichment of Tregs and promote the malignant progression of ESCC. In this study, we found a significant concordance between F. nucleatum infection and Tregs infiltration. Therefore, we propose the view that chronic infection of F. nucleatum may provide favorable conditions for long-term colonization of itself by recruiting Tregs and suppressing the immune response. At the same time, the massive enrichment of Treg may also weaken the immune response and assist in the long-term colonization of F. nucleatum. We analyzed the correlation between F. nucleatum infection with the clinicopathological characteristics and survival prognosis of the patients. F. nucleatum infection was found to be closely related to sex, smoking, drinking, degree of differentiation, depth of invasion, lymph node metastasis, and clinical stage. The degree of differentiation, depth of infiltration, lymph node metastasis, clinical stage, and F. nucleatum infection are independent risk factors affecting ESCC prognosis. Additionally, the survival rate and median survival time were significantly shortened in the F. nucleatum infection positive group. Therefore, we propose that long-term smoking and alcohol consumption cause poor oral and esophageal environments, thereby significantly increasing the risk of F. nucleatum infection. In turn, F. nucleatum infection and colonization may weaken the antitumor immune response through Treg enrichment and further assist in self-colonization, promoting the malignant progression of ESCC.	esophagus
Infection with Human Papillomavirus 18 Promotes Alkylating Agent-Induced Malignant Transformation in a Human Esophageal Cell Line.	The relationship between human papillomavirus (HPV) and esophageal cancer (EC) has been controversial, which may be caused by the difference in geographic regions of sample origin. Thus, we conducted a case-control study to find that HPV increased the risk of esophageal cancer, and the HPV18 detection rate is the highest (24.2%) among patients with EC, suggesting that HPV18 could be the most risk subtype of HPV infected. We then identified high-risk HPV18 and N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) to establish a model on the viral etiology cooperating with environmental carcinogens. Het-1A cells containing HPV18 were continuously exposed to MNNG or not; then the morphological phenotype and function assays were performed in 25th passage cells. MNNG promoted the proliferation and invasion abilities and inhibited apoptosis both in Het-1A-HPV18 and control group. However, the Het-1A-HPV18 had a stronger change in phenotypic features and formed more transformed foci in soft agar. Further, Western blot found p53 and p21 were down-regulated, and expression of c-Myc, MMP-2, and MMP-9 and Bcl-2/Bax ratio were up-regulated. Our results revealed that MNNG was easier to induce malignant transformation of Het-1A cells transfected with HPV18. It is good evidence for the close relationship between HPV and the etiology of EC, providing foundation for further study in molecular mechanism and specific intervention targets.	esophagus
Oncogenic enhancers drive esophageal squamous cell carcinogenesis and metastasis.	The role of cis-elements and their aberrations remains unclear in esophageal squamous cell carcinoma (ESCC, further abbreviated EC). Here we survey 28 H3K27ac-marked active enhancer profiles and 50 transcriptomes in primary EC, metastatic lymph node cancer (LNC), and adjacent normal (Nor) esophageal tissues. Thousands of gained or lost enhancers and hundreds of altered putative super-enhancers are identified in EC and LNC samples respectively relative to Nor, with a large number of common gained or lost enhancers. Moreover, these differential enhancers contribute to the transcriptomic aberrations in ECs and LNCs. We also reveal putative driver onco-transcription factors, depletion of which diminishes cell proliferation and migration. The administration of chemical inhibitors to suppress the predicted targets of gained super-enhances reveals HSP90AA1 and PDE4B as potential therapeutic targets for ESCC. Thus, our epigenomic profiling reveals a compendium of reprogrammed cis-regulatory elements during ESCC carcinogenesis and metastasis for uncovering promising targets for cancer treatment.	esophagus
[LncRNA ASB16-AS1 regulates the proliferation, migration and invasion of esophageal cancer cells by targeting miR-1258].	Objective: To investigate the effects of long-chain non-coding RNA ASB16 antisense RNA1 (ASB16-AS1) on the proliferation, migration and invasion of esophageal cancer cells by targeting microRNA (miR )-1258. Methods: Forty pairs of esophageal cancer tissues and matched adjacent tissues (distance of tumor margin>3 cm) resected in Xinxiang Central Hospital from May 2016 to July 2017 were collected. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expressions of ASB16-AS1 and miR-1258 in esophageal cancer tissues and adjacent tissues. The small interfering RNA negative control (si-NC), ASB16-AS1 small interfering RNA (si-ASB16-AS1), miR-negative control mimics (miR-NC), miR-1258 mimics (miR-1258), si-ASB16-AS1 and anti-miR-NC, si-ASB16-AS1 and anti-miR-1258, si-ASB16-AS1 and anti-miR-1258 were transfected into Eca109 cells, respectively. Methyl thiazolyl tetrazolium (MTT) was utilized to detect the cell viability. Transwell assays were applied to detect cell migration and invasion. Double luciferase reporting experiment and qRT-PCR were used to confirm the relationship between ASB16-AS1 and miR-1258. Results: The expression levels of ASB16-AS1 and miR-1258 in esophageal cancer tissues were 2.95±0.27 and 0.62±0.06, respectively. Compared with 1.00±0.06 and 1.00±0.07 in adjacent tissues, the difference was statistically significant (P<0.05). The cell viability of the si-NC group at 48 h and 72 h were 0.81±0.07 and 1.15±0.11, while those of si-ASB16-AS1 group were 0.46±0.04 and 0.62±0.06 (P<0.05). The numbers of cell migration and invasion in the si-NC group were 86.32±8.24 and 71.29±7.15, respectively, while those of si-ASB16-AS1 group were 43.22±4.31 and 32.36±3.58, respectively, the differences were statistically significant (P<0.05). The cell viability of the miR-NC group at 48 h and 72 h were 0.84±0.08, 1.18±0.12, while those of miR-1258 group were 0.55±0.05, 0.71±0.07 (P<0.05). The migration and invasion numbers of the miR-NC group were (83.15±8.31) and (75.33±7.51), while those of miR-1258 group were (49.58±4.23) and (38.42±3.84), respectively, the differences were statistically significant (P<0.05). The cell viability of the si-ASB16-AS1+ anti-miR-NC group at 48 h and 72 h were 0.45±0.04, 0.61±0.06, while those of si-ASB16-AS1+ anti-miR-1258 group were 0.72±0.07, 0.98±0.08; The migration and invasion numbers of cells in the si-ASB16-AS1+ anti-miR-NC group were 44.36±4.41 and 31.69±3.85, respectively, while those of si-ASB16-AS1+ anti-miR-1258 group were 72.65±7.27 and 61.22±6.14, respectively, and the differences were statistically significant (P<0.05). ASB16-AS1 targeted negative regulation of miR-1258 expression. Conclusions: ASB16-AS1 upregulates in esophageal cancer. ASB16-AS1 promotes the proliferation, migration and invasion of esophageal cancer cells by targeting miR-1258.	esophagus
Assessment of a diaphragm override strategy for robustly optimized proton therapy planning for esophageal cancer patients.	PURPOSE: To ensure target coverage in the treatment of esophageal cancer, a density override to the region of diaphragm motion can be applied in the optimization process. Here, we evaluate the benefit of this approach during robust optimization for intensity modulated proton therapy (IMPT) planning. MATERIALS AND METHODS: For 10 esophageal cancer patients, two robustly optimized IMPT plans were created either using (WDO) or not using (NDO) a diaphragm density override of 1.05 g/cm(3) during plan optimization. The override was applied to the excursion of the diaphragm between exhale and inhale. Initial robustness evaluation was performed for plan acceptance (setup errors of 8 mm, range errors of ±3%), and subsequently, on all weekly repeated 4DCTs (setup errors of 2 mm, range errors of ±3%). Target coverage and hotspots were analyzed on the resulting voxel-wise minimum (Vw(min) ) and voxel-wise maximum (Vw(max) ) dose distributions. RESULTS: The nominal dose distributions were similar for both WDO and NDO plans. However, visual inspection of the Vw(max) of the WDO plans showed hotspots behind the right diaphragm override region. For one patient, target coverage and hotspots improved by applying the diaphragm override. We found no differences in target coverage in the weekly evaluations between the two approaches. CONCLUSION: The diaphragm override approach did not result in a clinical benefit in terms of planning and interfractional robustness. Therefore, we do not see added value in employing this approach as a default option during robust optimization for IMPT planning in esophageal cancer.	esophagus
Clinical utility and applicability of circulating tumor DNA testing in esophageal cancer: a systematic review and meta-analysis.	Esophageal cancer is an aggressive malignancy with a relatively poor prognosis even after multimodality therapy. Currently, patients undergo a series of investigations that can be invasive and costly or pose secondary risks to their health. In other malignancies, liquid biopsies of circulating tumor DNA (ctDNA) are used in clinical practice for diagnostic and surveillance purposes. This systematic review summarizes the latest evidence for the clinical applicability of ctDNA technology in esophageal cancer. A systematic review of the literature was performed using MEDLINE, EMBASE, the Cochrane Review and Scopus databases. Articles were evaluated for the use of ctDNA for diagnosis and monitoring of patients with esophageal cancer. Quality assessment of studies was performed using the QUADAS-2 tool. A meta-analysis was performed to assess the diagnostic accuracy of sequencing methodologies. We included 15 studies that described the use of ctDNA technology in the qualitative synthesis and eight studies involving 414 patients in the quantitative analysis. Of these, four studies assessed its utility in cancer diagnosis, while four studies evaluated its use for prognosis and monitoring. The pooled sensitivity and specificity for diagnostic studies were 71.0% (55.7-82.6%) and 98.6% (33.9-99.9%), while the pooled sensitivity and specificity for surveillance purposes were 48.9% (29.4-68.8%) and 95.5% (90.6-97.9%). ctDNA technology is an acceptable method for diagnosis and monitoring with a moderate sensitivity and high specificity that is enhanced in combination with current imaging methods. Further work should demonstrate the practical integration of ctDNA in the diagnostic and surveillance clinical pathway.	esophagus
Identification of NOTCH4 mutation as a response biomarker for immune checkpoint inhibitor therapy.	BACKGROUND: Immune checkpoint inhibitor (ICI) therapy elicits durable antitumor responses in patients with many types of cancer. Genomic mutations may be used to predict the clinical benefits of ICI therapy. NOTCH homolog-4 (NOTCH4) is frequently mutated in several cancer types, but its role in immunotherapy is still unclear. Our study is the first to study the association between NOTCH4 mutation and the response to ICI therapy. METHODS: We tested the predictive value of NOTCH4 mutation in the discovery cohort, which included non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, esophagogastric cancer, and bladder cancer patients, and validated it in the validation cohort, which included non-small cell lung cancer, melanoma, renal cell carcinoma, colorectal cancer, esophagogastric cancer, glioma, bladder cancer, head and neck cancer, cancer of unknown primary, and breast cancer patients. Then, the relationships between NOTCH4 mutation and intrinsic and extrinsic immune response mechanisms were studied with multiomics data. RESULTS: We collected an ICI-treated cohort (n = 662) and found that patients with NOTCH4 mutation had better clinical benefits in terms of objective response rate (ORR: 42.9% vs 25.9%, P = 0.007), durable clinical benefit (DCB: 54.0% vs 38.1%, P = 0.021), progression-free survival (PFS, hazard ratio [HR] = 0.558, P < 0.001), and overall survival (OS, HR = 0.568, P = 0.006). In addition, we validated the prognostic value of NOTCH4 mutation in an independent ICI-treated cohort (n = 1423). Based on multiomics data, we found that NOTCH4 mutation is significantly associated with enhanced immunogenicity, including a high tumor mutational burden, the expression of costimulatory molecules, and activation of the antigen-processing machinery, and NOTCH4 mutation positively correlates activated antitumor immunity, including infiltration of diverse immune cells and various immune marker sets. CONCLUSIONS: Our findings indicated that NOTCH4 mutation serves as a novel biomarker correlated with a better response to ICI therapy.	esophagus
Simple Cancer Stem Cell Markers Predict Neoadjuvant Chemotherapy Resistance of Esophageal Squamous Cell Carcinoma.	BACKGROUND/AIM: Cancer stem cells (CSCs) contribute to resistance against neoadjuvant chemotherapy (NAC) in esophageal squamous cell carcinoma (ESCC). We conducted a retrospective observational study for the relationship between the expression levels of CSC markers in biopsy specimens prior to 5-fluorouracil plus cisplatin (FP)-NAC and the pathological responses. PATIENTS AND METHODS: We included 171 patients with ESCC who underwent the FP-NAC followed by radical resection. Biopsy specimens prior to the FP-NAC were obtained and immunochemically stained for CD44, CD133, and CD24. RESULTS: The biopsy specimens of the non-responders had the CD44(high)/CD24(low) expression at high levels, which was found as an independent predictor of not only FP-NAC resistance but also poor overall survival by multivariate analyses. CONCLUSION: CD44(high)/CD24(low) expression in the biopsy specimens prior to FP-NAC may be a predictor of FP-NAC resistance and poor prognosis of ESCC patients.	esophagus
Combining Preoperative Immunoinflammatory Scores and (18)F-Fluorodeoxyglucose Positron-emission Tomography Predicts Beneficiaries of Salvage Esophagectomy.	BACKGROUND: This study evaluated the prognostic value of preoperative immunoinflammatory scores and (18)F-fluorodeoxyglucose positron-emission tomography (FDG-PET) for patients undergoing salvage esophagectomy to identify suitable candidates for surgery. PATIENTS AND METHODS: Twenty-five patients undergoing salvage esophagectomy were included. The prognostic value of the preoperative C-reactive protein-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and maximum standardized FDG uptake value (SUVmax) were investigated. RESULTS: Multivariate analysis demonstrated high CAR to be an independent prognostic factor for overall survival (p=0.013). CAR had no association with clinicopathological variables, whereas the SUVmax was significantly positively associated with tumor aggressiveness. Multivariate analysis using residual tumor and the combination of CAR and SUVmax revealed both residual tumor (p=0.009) and high CAR/high SUVmax (p=0.016) to be independent prognostic factors for overall survival. CONCLUSION: Preoperative evaluation of CAR as an immunoinflammatory indicator and SUVmax as a marker of tumor aggressiveness will be useful to identify suitable candidates for this high-risk surgery.	esophagus
OSK-0028 in Patients With Esophageal Cancer Undergoing Esophagectomy: A Double-blind, Randomised Controlled Trial.	BACKGROUND/AIM: An excessive postoperative inflammatory response is correlated with the development of pneumonia and an unfavourable prognosis in patients undergoing esophagectomy for esophageal cancer. We assessed the influence of OSK-0028, a synthetic human ghrelin on inflammatory response and energy metabolism, on the postoperative course of patients following radical esophagectomy. PATIENTS AND METHODS: Esophageal cancer patients were randomly assigned to low-dose (LD; 0.25 μg/kg/h) or high-dose (HD; 0.5 μg/kg/h) intravenous OSK-0028 or placebo for 7 days after esophagectomy. The primary endpoint was serum interleukin-6 level on postoperative day (POD) 3. RESULTS: A total of 75 patients were enrolled (23 LD, 26 HD, 26 placebo). The median interleukin-6 levels on POD 3 were 40.95, 35.85, and 64.50 pg/ml in the placebo, LD, and HD groups, respectively, with no significant differences (p=0.78). Postoperative complications did not differ between groups. Bodyweight loss was significantly lower in patients receiving OSK-0028 than in those receiving placebo (-0.17% vs. 1.78%, p=0.043). CONCLUSION: Although OSK-0028 did not attenuate inflammatory response after esophagectomy, it prevented postoperative bodyweight loss.	esophagus
Tissue distribution of γδ T cell subsets in oesophageal adenocarcinoma.	The global obesity epidemic is contributing to increased prevalence of diseases fuelled by chronic inflammation, including cancer. Oesophageal adenocarcinoma (OAC) is an obesity-associated malignancy with increasing prevalence, dismal prognosis, and severely dysregulated immune processes. We previously reported that αβ T cells migrate to omentum and liver in OAC and contribute to inflammation in these tissues. Here, we assessed the tissue distribution and phenotype of gamma/delta (γδ) T cells in the blood, omentum, liver and tumour of OAC patients. Our data show that the Vδ1 and Vδ3 subsets of γδ T cells are most prevalent in omentum and liver of OAC patients. Furthermore, γδ T cells are predominantly pro-inflammatory in these tissues, and co-express IFN-γ and IL-17. Moreover, γδ T cells exhibit cytotoxic capabilities in OAC omentum and liver. This study provides the first indication that γδ T cells contribute to obesity-associated inflammation in OAC and might be exploited therapeutically.	esophagus
Prognostic value of platelet-related measures for overall survival in esophageal squamous cell carcinoma: A systematic review and meta-analysis.	Platelet-related measures are considered important in predicting long-term outcomes in patients with esophageal squamous cell carcinoma (ESCC). We performed a systematic electronic research of studies evaluating the prognostic value of platelet-related measures in ESCC in Google Scholar, PubMed, Cochrane Library, and Embase. Then, to synthesize publications exploring the association between platelet-related measures and survival outcomes in ESCC, a meta-analysis was conducted using hazard ratio and 95 % confidence interval. In total, 14 retrospective articles were included in this study. Among them, 4 and 10 have evaluated the clinical impact of platelet count and platelet-to-lymphocyte ratio (PLR), respectively. Further, three studies reported about platelet distribution width (PDW) and mean platelet volume (MPV). Based on the synthesized results, high PLR was significantly associated with poor overall survival (OS). However, platelet count, PDW, and MPV were non-independent prognostic factors for OS. The Begg's funnel plots for PLR, PDW, and MPV indicated low publication bias.	esophagus
Interplay and cooperation between SREBF1 and master transcription factors regulate lipid metabolism and tumor-promoting pathways in squamous cancer.	Squamous cell carcinomas (SCCs) comprise one of the most common histologic types of human cancer. Transcriptional dysregulation of SCC cells is orchestrated by tumor protein p63 (TP63), a master transcription factor (TF) and a well-researched SCC-specific oncogene. In the present study, both Gene Set Enrichment Analysis (GSEA) of SCC patient samples and in vitro loss-of-function assays establish fatty-acid metabolism as a key pathway downstream of TP63. Further studies identify sterol regulatory element binding transcription factor 1 (SREBF1) as a central mediator linking TP63 with fatty-acid metabolism, which regulates the biosynthesis of fatty-acids, sphingolipids (SL), and glycerophospholipids (GPL), as revealed by liquid chromatography tandem mass spectrometry (LC-MS/MS)-based lipidomics. Moreover, a feedback co-regulatory loop consisting of SREBF1/TP63/Kruppel like factor 5 (KLF5) is identified, which promotes overexpression of all three TFs in SCCs. Downstream of SREBF1, a non-canonical, SCC-specific function is elucidated: SREBF1 cooperates with TP63/KLF5 to regulate hundreds of cis-regulatory elements across the SCC epigenome, which converge on activating cancer-promoting pathways. Indeed, SREBF1 is essential for SCC viability and migration, and its overexpression is associated with poor survival in SCC patients. Taken together, these data shed light on mechanisms of transcriptional dysregulation in cancer, identify specific epigenetic regulators of lipid metabolism, and uncover SREBF1 as a potential therapeutic target and prognostic marker in SCC.	esophagus