crossing96/oncoscreening huggingface dataset:
The Role of Mitochondrial DNA in Modulating Chemoresistance in Esophageal Cancer: Mechanistic Insights and Therapeutic Potential.	Chemotherapy remains a cornerstone in the treatment of esophageal cancer (EC), yet chemoresistance remains a critical challenge, leading to poor outcomes and limited therapeutic success. Mitochondrial DNA (mtDNA) has emerged as a pivotal player in mediating these responses, influencing cellular metabolism, oxidative stress regulation, and apoptotic pathways. This review provides a comprehensive overview of the mechanisms by which mtDNA alterations, including mutations and copy number variations, drive chemoresistance in EC. Specific focus is given to the role of mtDNA in metabolic reprogramming, including its contribution to the Warburg effect and lipid metabolism, as well as its impact on epithelial-mesenchymal transition (EMT) and mitochondrial bioenergetics. Recent advances in targeting mitochondrial pathways through novel therapeutic agents, such as metformin and mitoquinone, and innovative approaches like CRISPR/Cas9 gene editing, are also discussed. These interventions highlight the potential for overcoming chemoresistance and improving patient outcomes. By integrating mitochondrial diagnostics with personalized treatment strategies, we propose a roadmap for future research that bridges basic mitochondrial biology with translational applications in oncology. The insights offered in this review emphasize the critical need for continued exploration of mtDNA-targeted therapies to address the unmet needs in EC management and other diseases associated with mitochondria.	esophagus
Radical surgery versus definitive radiotherapy in treatment of locoregional upper esophageal squamous cell carcinoma.	BACKGROUNDS: Current consensus guidelines lack robust evidence to advocate the optimal treatment approach for locoregional upper esophageal squamous cell carcinoma (L-UESCC). The purpose of this study was to conduct an in-depth investigation of the treatment patterns, outcomes, and prognostic factors among patients with L-UESCC. METHODS: Consecutive patients diagnosed with L-UESCC who underwent curative-intent treatment at two cancer centers from January 2013 to December 2018 were enrolled in this study. To compare overall survival (OS) and conduct prognostic analysis, we employed the Kaplan-Meier method, Cox regression models, and propensity score matching (PSM). RESULTS: In the entire cohort, 247 patients (64.2%) received definitive radiotherapy, whereas 138 patients (35.8%) underwent radical surgery. Multivariable Cox analysis revealed that T stage, N stage, and tumor length were independent predictors of OS. The Kaplan-Meier analysis demonstrated comparable median OS between the surgical and radiotherapy groups both before and after PSM adjustment. Before PSM, the median OS was 27.0 months in the surgical group and 29.0 months in the radiotherapy group (P = 0.48); after PSM, it was 23.0 and 30.0 months respectively (P = 0.38). Notably, the combination of chemotherapy with radiotherapy was associated with a significant survival benefit over radiotherapy monotherapy (median OS 36.0 versus 20.0 months, P = 0.005). In chemotherapy-naïve subgroups, surgery conferred a significant survival advantage over radiotherapy (P = 0.016), particularly in stage I-II (P = 0.003), but not in stage III (P = 0.54). CONCLUSIONS: In patients with L-UESCC, surgical resection and definitive radiotherapy yielded similar OS results. Formulating personalized treatment strategies requires a multidisciplinary approach integrating systemic and local therapies.	esophagus
Innovative staining for endoscopic screening of early esophageal cancer and precancerous lesions: a preclinical study.	"BACKGROUND: Lugol's iodine staining (LIS) solution is used to assist in esophageal chromoendoscopy. Mucosal irritation often results in uncomfortable symptoms and the risk of allergy. In the present study, we developed an extremely low-irritation, easy-to-use mucosal staining solution using polyvinyl pyrrolidone-iodine (PVP-I). This study aimed to evaluate its mucosal staining capacity and biocompatibility. METHODS: The mucosal staining capacity was evaluated using postoperative esophageal endoscopic submucosal dissection (ESD) specimens. After elution with vitamin C solution, the specimens were sprayed with LIS as a self-control. The effects on the ""lesion area"" outlined between the innovative staining and LIS were examined by the intraclass correlation coefficient (ICC) and rank-sum test. To evaluate the biocompatibility, esophageal perfusion was performed with the mice, and the esophagus and stomach were anatomized at different time points for pathological analysis. RESULTS: A total of 53 esophageal ESD specimens were stained at the endoscopy center of West China Hospital. Compared with the same concentration of LIS, the PVP-I solutions showed similar staining effects in terms of the lesion area outlined [ICC = 0.998 (> 0.75), P = 0.733 (> 0.05)]. In live mouse experiments with esophageal perfusion, PVP-I was safer and less irritable to the esophageal gastric mucosa than LIS was, with a lower mucosal damage index (UI) and fewer inflammatory cells in pathological analysis at various time points. CONCLUSIONS: The innovative PVP-I staining demonstrated effectiveness, safety, and feasibility as a mucosal staining solution for screening esophageal lesions. Further clinical studies will be carried out in the future."	esophagus
Nal-IRI/LV5-FU versus paclitaxel as second-line therapy in patients with metastatic esophageal squamous cell carcinoma (PRODIGE 62-FFCD 1701-OESIRI).	BACKGROUND: Metastatic esophageal squamous cell carcinoma (mESCC) patients with disease progression after platinum-based first-line chemotherapy (CT) +/- immune checkpoint inhibitors (ICI) may benefit from second-line CT, mostly based on paclitaxel and irinotecan, but no randomized trial has compared these regimens. PATIENTS AND METHODS: PRODIGE 62-OESIRI is a multicenter, open-label, randomized phase II trial evaluating the efficacy and safety of nanoliposomal irinotecan (Nal-IRI) plus 5FU versus paclitaxel as second-line CT in mESCC. The primary endpoint was to achieve overall survival (OS) of 60 % at 9 months. RESULTS: Between March 2019 and July 2023, 106 pts were randomized. Median age was 65.6 years, 83.0 % men and 29.2 %/58.5 %/12.3 % of ECOG PS 0/1/2, respectively. As prior treatment, 48.6 % had chemoradiation, 41.9 % CT alone and 9.5 % CT plus ICI. OS at 9 months was 34.0 % [90 %CI: 22.9-46.5] and 39.2 % [90 %CI: 27.7-51.7] in the 5FU Nal-IRI and paclitaxel arms, respectively. The primary endpoint was not met. Median progression-free survival was 2.4 [95 %CI: 2.1-3.6] and 2.1 [95 %CI: 1.9-3.3] months, and median OS 7.1 [95 %CI: 5.2-8.3] and 6.6 [95 %CI: 4.8-10.3] months, respectively. Overall, 51.0 % and 38.5 % of patients experienced at least one grade 3-4 treatment-related adverse events (neuropathy: 2.0 vs. 7.7 %, diarrhea: 16.3 % vs. 0 % and vomiting: 10.2 vs. 0 %), in the 5FU Nal-IRI and paclitaxel arms, respectively. Treatment was discontinued for toxicity in 10.4 % versus 3.9 % in the 5FU Nal-IRI and paclitaxel arm, respectively. CONCLUSIONS: PRODIGE 62-OESIRI trial showed low efficacy of paclitaxel and 5FU Nal-IRI in the 2nd line treatment of mESCC, though paclitaxel provided a better safety profile. Trial registration NCT03719924.	esophagus
Chromatin Remodeler RSF1 as an Oncogenic Driver and Therapeutic Target in Esophageal Squamous Cell Carcinoma.	Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy, ranking eleventh in incidence and seventh in mortality globally. Remodeling and Spacing factor 1 (RSF1), a chromatin remodeling factor, is frequently overexpressed in various tumors and correlates with poor prognosis. This study, combining public database analysis and clinical sample validation, reveals significantly elevated RSF1 expression in ESCC tumor tissues, confirmed further in an ESCC orthotopic model. Functional assays show that RSF1 knockout (KO) significantly inhibits ESCC cell proliferation, migration, invasion, and in vivo tumor growth, while reintroducing RSF1 restores its oncogenic effects. Proteomic analysis highlights that RSF1 KO disrupts pathways associated with cell cycle control, apoptosis, and focal adhesion. Experimentally, RSF1 KO induces apoptosis and G2/M arrest, establishing its essential role in ESCC progression. Collectively, these findings establish RSF1 as an oncogenic driver and a promising therapeutic target in ESCC.	esophagus
Characterization of tertiary lymphoid structure identifies competitive binding of CD40 and STING with TRAF2 driving IRF4-mediated B cell activation in esophageal squamous cell carcinoma.	Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with a dismal prognosis. Hitherto, little has been known regarding the clinical implications of tertiary lymphoid structures (TLS) and its biological mechanisms of antitumor effect on treatment-naïve ESCC. We herein identified the presence of TLS as an independent factor for favorable survival. By characterizing the immune infiltration and genomic profiles based on transcriptomic datasets, we found TLS abundant in enriched B cells with IRF4 as a signature gene. Increased expression of IRF4 and its positive correlation with STING in activating tumor-infiltrating B cells were also investigated using a single-cell RNA sequencing dataset. CD40 as a co-regulator of IRF4 and TLS formation, in vitro experiments were conducted to further demonstrate the competitive binding relationships between CD40 and STING with TRAF2 in promoting IRF4 expression and B cell activation via the non-canonical NF-kB signaling pathway, in which CD40 reduced STING ubiquitination while promoting its phosphorylation. Our data provided deeper insights into the potential role of activated B cells and TLS in ESCC, with implications for the development of biomarkers and therapeutic targets.	esophagus
The immune signatures predict gastric/gastroesophageal junction cancer response to first-line anti-PD-1 blockade or chemotherapy.	BACKGROUND: Anti-programmed cell death-1 (PD-1) immunotherapy and platinum-based chemotherapy are key components of first-line treatment for advanced Gastric or Gastroesophageal Junction (G/GEJ) cancer. However, the role of immune cells infiltrating the tumor microenvironment (TME) in predicting both therapy responses is still unclear. METHODS: ORIENT-16 is a randomized, double-blind, placebo-controlled, phase 3 clinical trial, and enrolled 650 patients with unresectable locally advanced or metastatic G/GEJ cancer between January 3, 2019, and August 5, 2020. For patients enrolled from the First Affiliated Hospital of Zhejiang University School of Medicine, we analyzed progression-free survival(PFS) and overall survival (OS) based on PD-L1 expression and landmark analysis, and developed a multiplexed immunofluorescence (mIF) assay for CD4, CD8, PD-L1, CD68 and FoxP3 coupled with digital image analysis and machine learning to assess prognostic survival associations of immune cells. RESULTS: A total of 54 eligible patients were enrolled in this study, 35 received sintilimab plus platinum-based chemotherapy and 19 received placebo plus platinum-based chemotherapy. For patients with PD-L1 combined positive score (CPS) < 10, survival disparities between anti-PD-1 immunotherapy and chemotherapy emerged 300 days post-treatment. High PD-L1 expression correlated with longer survival in anti-PD-1 therapy but less benefit in platinum-based chemotherapy. The mIF analysis also demonstrated significantly higher stromal PD-L1 density in immunotherapy responders, but tended to be lower in chemotherapy responders. Besides, high tumor stromal CD8 expression could be used as a positive biomarker in anti-PD-1 immunotherapy, and high tumor stromal CD4 expression was found associated with worse prognosis in platinum-based chemotherapy. CONCLUSIONS: Increased PD-L1 expression was associated with an increased effect on anti-PD-1 immunotherapy and reduced benefit from chemotherapy. The signature of TME immune cells has the potential to predict the response of anti-PD-1 immunotherapy and chemotherapy in G/GEJ cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03745170.	esophagus
Increased reflux secondary bile acids are associated with changes to the microbiome and transcriptome in Barrett's esophagus.	Bile acids are a major component of gastro-esophageal refluxate, thought to contribute to the development of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). As the microbiome shifts with EAC progression and bile acids influence bacterial composition, we examined these connections in a multi-center, cross-sectional study. We analyzed biospecimens from patients undergoing endoscopy using LC-MS to quantify bile acids in gastric aspirates, 16S rRNA sequencing for tissue microbiome profiling, and RNA sequencing on BE or cardia tissue. Among 153 patients (52 controls, 101 BE: 50 no dysplasia, 10 indefinite, 17 low-grade dysplasia, 17 high-grade dysplasia, and 7 EAC), we observed increased Streptococcus in BE tissue; dysplasia and EAC were associated with more Lactobacillus and decreased Actinomyces and other genera. Refluxate bile acids were mainly conjugated, indicating minimal bacterial metabolism, while BE patients had elevated secondary bile acid levels. Streptococcus correlated with upregulation of IL6, FGF2, and HGF, and decreased Actinomyces showed the most associations with gene expression, including the oxidative phosphorylation pathway. We identified two distinct BE gene expression clusters independent of histology, bile acid, or microbiome composition. These findings suggest bile acids shape the BE microbiome and associate with gene expression changes potentially relevant to EAC development.	esophagus
Efficacy and safety of tislelizumab in patients with advanced esophageal squamous cell carcinoma: a systematic review and meta-analysis.	BACKGROUND: Tislelizumab, a PD-1-targeting monoclonal antibody, can potentially treat advanced esophageal squamous cell carcinoma (ESCC). Using pooled clinical data, this study evaluates Tislelizumab's efficacy and safety in advanced ESCC. METHODS: This review followed PRISMA guidelines, with a comprehensive search conducted across PubMed, ProQuest, EBSCOhost, and Google Scholar for clinical trials involving ESCC patients treated with Tislelizumab. Primary endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). We evaluated the study quality using the Cochrane Risk of Bias and ROBINS-I tools. Data extraction and pooling were performed using R for single-arm studies and RevMan 5.4 for RCTs. Outcomes were analyzed using pooled medians, hazard ratios for OS and PFS, and relative risks for ORR, DCR, and adverse events. RESULTS: Four studies with 1,202 patients met inclusion criteria. The risk of bias was low to moderate. Pooled data indicate a median OS of 8.6 months and PFS of 4.75 months in the Tislelizumab group, with an overall ORR of 0.40 (95% CI: 0.20-0.61) and DCR of 0.64 (95% CI: 0.36-0.88). Tislelizumab significantly improved OS (HR 0.68, 95% CI: 0.59-0.78, p < 0.0001), PFS (HR 0.71, 95% CI: 0.54-0.93, p = 0.01), ORR (RR 1.65, 95% CI: 1.22-2.24, p = 0.001), and DCR (RR 1.11, 95% CI: 1.04-1.18, p = 0.001) compared to standard chemotherapy. Pooled rates of grade 3 or more AEs and serious AEs were 0.56 (95% CI: 0.17-0.92) and 0.28 (95% CI: 0.10-0.50), respectively. There were no significant differences in grade 3 and serious AEs between Tislelizumab and standard chemotherapy. The most common AEs reported included hematologic toxicities, gastrointestinal issues, metabolic disturbances, and biochemical abnormalities. CONCLUSION: Tislelizumab improves survival and response in advanced ESCC patients, particularly when combined with chemotherapy, with an acceptable safety profile. These findings support its continued use in ESCC, though further investigation is warranted due to the limited number of studies. TRIAL REGISTRATION: CRD42024564367.	esophagus
Application of machine learning based on habitat imaging and vision transformer to predict treatment response of locally advanced esophageal squamous cell carcinoma following neoadjuvant chemoimmunotherapy: a multi-center study.	OBJECTIVE: Current medical examinations and biomarkers struggle to assess the efficacy of chemoimmunotherapy (nICT) for locally advanced esophageal squamous cell carcinoma (ESCC). This study aimed to develop a machine learning model integrating habitat imaging and deep learning (DL) to predict the treatment response of ESCC patients to nICT. METHODS: The study retrospectively collected 309 ESCC patients from 6 medical centers, divided into training and external validation cohorts. For habitat imaging analysis, intratumoral subregions were clustered using the K-means clustering method. DL features from intratumoral and peritumoral subregions were extracted by Vision Transformer (ViT) respectively and then subjected to feature selection. Subsequently, 11 machine learning models were constructed for predictive model. The model's performance was evaluated using the area under the curve (AUC), decision curve analysis (DCA), calibration curve, and accuracy. RESULTS: A total of 18 DL features were selected. The model of ExtraTrees, which was optimal, demonstrated superior performance with AUCs of 0.917 in training cohort and 0.831 in external validation cohort. Similarly, ExtraTrees showed good predictive capabilities in patients undergoing 2 cycles of nICT with AUC of 0.862 in validation cohort. This model also showed good calibration for prediction probability and satisfied clinical value on DCAs. Finally, the SHapley Additive exPlanations method elucidated the model's precise predictions. CONCLUSION: The ExtraTrees model leveraging habitat imaging and ViT offered a non-invasive and accurate method to predict pathological response to nICT, guiding personalized treatment strategies, and decreasing the risk of immune-related adverse effects.	esophagus
Neoadjuvant chemoradiation with camrelizumab and nimotuzumab for initially inoperable esophageal squamous cell carcinoma: A single-arm phase 2 trial.	BACKGROUND: Neoadjuvant regimen with a high surgical conversion rate was warranted for initially inoperable patients with locally advanced esophageal squamous cell carcinoma (LAESCC). To evaluate the efficacy and safety of neoadjuvant chemoradiotherapy combined with camrelizumab and nimotuzumab (NCRCN) followed by surgery in initially inoperable patients with LAESCC. METHODS: This cohort study was a prospective, one-arm, phase 2 study from December 2021 to December 2023. All patients were supposed to receive neoadjuvant chemoradiotherapy (41.4Gy/23 fractions plus weekly nab-paclitaxel (50 mg/m(2)) and carboplatin (AUC=2)), camrelizumab (200 mg every three weeks), and nimotuzumab (200 mg every three weeks). The primary endpoint was the 1-year progression-free survival (PFS) rate. RESULTS: Thirty-five patients were enrolled and underwent neoadjuvant therapy (27 men [77 %]; 8 women [23 %]; median [IQR] age, 67[61-73] years). The surgical conversion rate was 86 % (30/35) with R0 resection rate of 97 % (29/30). The pathological complete response (pCR) rate and major pathologic response (MPR) rate were 37 % (11/30), and 53 % (16/30). After a median observation time of 18.5 months, the total cohort of 1-year PFS and overall survival (OS) rates were 67 % and 80 %, respectively. Those main adverse events of more than grade 3 were lymphopenia (77 %, 27/35), radiation esophagitis (17 %, 6/35), abnormal liver function (11 %, 4/35), and neutropenia (9 %, 3/35). Patients with pCR after neoadjuvant therapy showed increased infiltration of CD8 +T cell and decreased FOXP3 +Treg cell density variation in the tumor microenvironment (P < 0.05). High variation of CD8 +T cell density in tumor was significantly associated with better PFS (HR, 7.69; P = 0.01). CONCLUSIONS: NCRCN regimen was a promising treatment strategy with a high surgical conversion rate in initially inoperable patients with LAESCC. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER: NCT05355168.	esophagus
Association of Oral Health and Periodontal Disease With Oesophageal Cancer: A Nationwide Population-Based Study.	AIM: Oral dysbiosis and periodontal inflammation might play a role in oesophageal carcinogenesis via the translocation of periodontal pathogens. We aimed to assess whether poor oral health is associated with oesophageal cancer. METHODS: We conducted a population-based case-control study using the Korean National Health Insurance Service database to evaluate poor oral health as the exposure and oesophageal cancer as the outcome. Two study designs were employed: (1) oral health analysis using screening data, and (2) periodontal disease analysis using claims data. Oesophageal cancer cases were matched to cancer-free controls at a 1:4 ratio using extensive propensity score matching. RESULTS: After matching, 4238 cases and 16,904 controls were included in the oral health analysis, and 18,905 cases and 75,604 controls were included in the claims-based analysis. In the multivariable analysis, missing teeth (adjusted OR [aOR], 1.16; 95% confidence interval [CI]: 1.08-1.25) and periodontal disease (aOR, 1.05; 95% CI: 1.01-1.09) were both significantly associated with increased odds of oesophageal cancer. Poor oral hygiene practices including infrequent brushing, irregular bedtime brushing, lack of interdental cleaning and dental visits also showed positive associations. Subgroup analyses showed consistent associations across obesity and smoking status, whereas the associations were less consistent in women, the elderly and non-drinkers. CONCLUSION: Poor oral health indicators including inadequate oral hygiene behaviours were associated with elevated odds of oesophageal cancer, suggesting the potential utility of oral health status in risk stratification.	esophagus
H-chain ferritin-based magnetic nanoparticles targeting CD71 for magnetic resonance imaging diagnosis of esophageal squamous cell carcinoma and its precancerous lesions.	Esophageal squamous cell carcinoma (ESCC) represents a globally prevalent malignancy characterized by a poor prognosis, largely due to the challenges that patients face in tolerating invasive diagnostic procedures. Therefore, it is imperative to explore strategies to enhance the early diagnostic rate for patients with ESCC. Based on the property of H-chain ferritin-based magnetic ferritin nanoparticles (M-HFn) as contrast agents that can target cluster of differentiation 71 (CD71), this study provides a comprehensive evaluation of the expression levels and diagnostic potential of CD71 to investigate the feasibility of utilizing M-HFn for non-invasive diagnosis. Following the synthesis and the characterization of M-HFn, an orthotopic mouse model is developed to simulate the progression of ESCC. Subsequently, magnetic resonance imaging (MRI) scans are conducted after administering M-HFn to the mice. The results indicate a progressive increase of CD71 expression in tissues, transitioning from normal epithelium to esophageal squamous precancerous lesions (ESPL) and ultimately to ESCC. M-HFn injected into the mice selectively target cells with heightened CD71 expression, resulting in accumulation at the lesion sites. Consistent with pathological diagnoses, MRI images demonstrate a reduction in signal intensity at the lesion site in T(2)-weighted sequences, thereby facilitating the visualization of ESCC and ESPL. CD71 demonstrates high accuracy and specificity as a diagnostic target, positioning M-HFn-mediated targeted diagnostic strategy as a promising approach for the early detection of ESCC, with the potential to significantly improve patient prognosis.	esophagus