crossing96/oncoscreening huggingface dataset:
Immunohistochemical biomarker scoring in gastroesophageal cancers: Can computers help us?	The increasing complexity of cancer diagnostics and treatment selection has placed a growing burden on pathologists, particularly in the evaluation of immunohistochemical (IHC) biomarkers. In gastroesophageal cancers (GEC), both adenocarcinoma and squamous cell carcinoma subtypes, multiple prognostic and predictive biomarkers must be assessed to guide therapy. These evaluations require meticulous scoring, are time-consuming, and suffer from inter- and intra-observer variability. Given the worldwide shortage of pathologists, artificial intelligence (AI)-based tools have emerged as a potential solution to enhance efficiency and accuracy in biomarker scoring. This review aims to answer the question captured in its title: can AI help us in IHC biomarker scoring in GEC, and if so, how? A search of PubMed and Google Scholar was conducted to identify relevant studies. The analysis reveals that AI has demonstrated promise in improving reproducibility and reducing pathologist workload for biomarkers such as PD-L1 and HER2, although its applications in GEC remain limited compared to other cancer types. In parallel, predictive computational approaches are emerging that could revolutionize biomarker scoring altogether. By alleviating the burdens of complex scoring systems and costly additional assays, AI could have the potential to significantly enhance pathology practice in GEC biomarker evaluation.	esophagus
Specialist palliative care is associated with reduced healthcare utilization in patients with advanced esophageal and gastric cancer: a nationwide register-based study.	BACKGROUND AND PURPOSE: Esophageal and gastric cancer patients, with poor prognoses and complex symptom burdens, require comprehensive end-of-life care. This study evaluated the impact of specialist palliative care (SPC) on end-of-life healthcare utilization. MATERIAL AND METHODS: We retrospectively analyzed nationwide healthcare utilization data for all adults who died of esophageal or gastric cancer in Finland in 2019, using National Health and Social Care Registers. Patients were compared based on timing of first SPC contact: early (> 30 days before death) or no/late (≤ 30 days). RESULTS: The cohort included 732 patients (median age 72 years), with 233 (32%) having SPC contact, including 156 (21%) with early SPC. Most patients (79%) had late/no SPC. The median time for first SPC contact was 120 days before death for early SPC group, and 12 days for no/late group, p < 0.001. Early SPC group, compared to no/late SPC, had fewer emergency department contacts (44% vs. 60%, p < 0.001) and secondary care hospitalizations (32% vs. 61%, p < 0.001) in the last month. Early SPC increased access to hospital-at-home (56% vs. 6%, p < 0.001) and SPC wards (19% vs. 4%, p < 0.001). Patients with early SPC died more often in SPC wards (19% vs. 4%,p < 0.001). Overall, 122 (17%) received hospital-at-home care, and were more likely to die at home (19% vs. 11%,p = 0.011) or in SPC wards (15% vs. 5%, p < 0.001). CONCLUSIONS: Few patients with advanced esophageal or gastric cancer receive SPC. Early SPC was associated with reduced healthcare utilization and improved access to SPC services, highlighting the importance of timely SPC initiation.	esophagus
Pretreatment CALLY index as promising novel biomarker in the prediction of surgical and oncological outcomes in esophageal cancer: a multi-center retrospective cohort study.	BACKGROUND: Esophageal cancer (EC) is a global health challenge with high mortality rates. The traditional TNM staging system is limited in its ability to provide accurate prognostic predictions. This study aimed to investigate the utility of the C-reactive protein-albumin-lymphocyte (CALLY) index in the evaluation of mid- to long-term outcomes in patients undergoing esophagectomy. METHODS: We conducted a multi-center retrospective cohort study of 657 EC patients admitted between 2010 to 2024, with 553 patients from Shanghai General Hospital (training cohort) and 104 from Shanghai Sixth People's Hospital (validation cohort). Associations between the CALLY and overall survival (OS)/disease-free survival (DFS) were evaluated using multivariable-adjusted Cox regression analyses. RESULTS: Patients with CALLY index > 2.55 were associated with significantly improved OS (adjusted hazard ratio [HR]: 0.55, 95% confidence interval [CI]: 0.43-0.71) and DFS (HR: 0.51, 0.40-0.65), independent of clinical risk factors. Incorporating CALLY index into clinical prediction models significantly enhanced discriminative ability (area under the receiver operating characteristic curve [AUROC] of OS: 0.719-0.752; AUROC of DFS: 0.745-0.788, P < 0.01). In the validation cohort, the same associations were also observed (HR of OS: 0.57, 95% CI: 0.42-0.78; HR of DFS: 0.53, 95% CI: 0.40-0.71). In both cohorts, CALLY index > 2.55 were associated with significantly reduced risk of recurrence. CONCLUSIONS: The CALLY index emerges as a cost-effective prognostic tool integrating inflammation-nutrition-immunity parameters. Its preoperative integration with tumor, node, and metastasis staging and other well-known risk factors might optimize risk stratification and guide personalized therapeutic strategies for EC patients undergoing esophagectomy.	esophagus
Survival Comparison Between Open and Thoracoscopic Esophagectomy for Esophageal Squamous Cell Carcinoma Stratified by Pathological Tumor-Node-Metastasis Stage: An Overlap Weighting Analysis.	BACKGROUND: The survival differences between open esophagectomy (OE) and thoracoscopic esophagectomy (TE) for patients with esophageal squamous cell carcinoma (ESCC) across different pathological tumor-node-metastasis stage (pStage) remain controversial. Therefore, this study aims to compare long-term survival between OE and TE in patients with ESCC across different pStage groups using overlap weighting. PATIENTS AND METHODS: This ambispective cohort study analyzed patients with ESCC who underwent OE or TE between January 2015 and December 2016 at a tertiary hospital in Henan Province. The primary endpoints were 5-year overall survival (OS), while disease-free survival (DFS) was a secondary endpoint. Operation safety was also assessed. Cox regression was used after overlap weighting, with sensitivity analysis by propensity score matching. RESULTS: The study cohort included 1715 eligible patients. Median survival was 66.07 months for pStage 0/I/II and 38.47 months for pStage III/IV. Overlap-weighted Cox regression showed significant survival benefits of TE. In the pStage 0/I/II group, the hazard ration (HR) for OS was 0.43 (95% confidence intervals, CI: 0.33-0.57) and for DFS was 0.44 (95% CI: 0.33-0.58). In the pStage III/IV group, the HR for OS was 0.70 (95% CI: 0.57-0.87) and for DFS was 0.73 (95% CI: 0.58-0.90). TE reduced blood loss, increased lymph node dissection, and lowered anastomotic leaks, though it required longer operative time and higher costs (P < 0.05). CONCLUSIONS: TE improved OS and DFS and operation safety compared with OE in patients with early and advanced-stage ESCC after adjusting for confounding factors.	esophagus
Inhibition of Phosphoglycerate Kinase 1 Enhances Radiosensitivity of Esophageal Squamous Cell Carcinoma to X-rays and Carbon Ion Irradiation.	BACKGROUND: Radiotherapy is crucial for managing esophageal squamous cell carcinoma (ESCC). This research explored the potential and mechanism of enhancing ESCC radiosensitivity through targeting phosphoglycerate kinase 1 (PGK1). METHODS: After ESCC cells were exposed to X-rays and C-ions, hub genes were identified through proteomic analysis and bioinformatics. To elucidate PGK1's function, small interfering RNAs and plasmids were used to silence and overexpress PGK1 in two human ESCC cell lines. Plate colony formation, cell counting kit 8, and 5-ethynyl-2'-deoxyuridine assays were conducted to detect cell proliferation after irradiation with different linear energy transfer rays (X-rays and carbon ions). Flow cytometry was used to assess radiation-induced perturbations in the cell cycle, apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential. Western blotting was performed to detect the protein expressions of protein kinase B (Akt), phosphorylated protein Kinase B (pAkt), mammalian target of rapamycin (mTOR), and phosphorylated mammalian target of rapamycin (pmTOR). RESULTS: Proteomics and bioinformatics analyses revealed that PGK1 plays a key role in modulating ESCC radiosensitivity. Knockdown of PGK1 resulted in the suppression of cancer cell proliferation and viability, promoted apoptotic processes, and demonstrated a synergistic anti-tumor effect in conjunction with radiation. Conversely, overexpression of PGK1 promoted cancer cell growth and increased radiation resistance. This may be attributed to the accumulation of ROS and the inhibition of Akt/mTOR pathway following PGK1 inhibition. CONCLUSION: Targeting PGK1 may be an effective strategy to increase ESCC radiation sensitivity, offering a promising strategy for improving treatment outcomes.	esophagus
USP49 undergoes liquid-liquid phase separation and stabilizes RPA70 to induce radioresistance through homologous recombination repair in esophageal squamous cell carcinoma.	Radiotherapy is crucial in the comprehensive management of esophageal squamous cell carcinoma (ESCC). Nevertheless, its efficacy is compromised by the emergence of radioresistance, leading to poor prognoses. Accumulating research has underscored the critical role of deubiquitinases (DUBs) in modulating radiosensitivity. This study aimed to identify potential DUBs that mediate radioresistance in ESCC and to elucidate the underlying regulatory mechanisms. Our research has identified deubiquitinase USP49 as a critical regulator of radiosensitivity in ESCC both in vivo and in vitro. Elevated USP49 expression was related to a poorer prognosis in ESCC patients receiving chemoradiotherapy. Mechanistically, the ataxia telangiectasia mutated (ATM) promotes liquid-liquid phase separation (LLPS) of USP49 and its recruitment at DNA double-strand breaks (DSBs) upon ionizing radiation (IR) exposure. USP49 deubiquitinates and recruits RPA70 to DSBs along with Rad51, thereby promoting homologous recombination (HR) repair. Moreover, p53 further augments the transcription of USP49 upon IR exposure. Our findings clarify a previously unrecognized mechanism by which USP49 modulates HR and radioresistance, proposing that targeting USP49 could potentially enhance radiosensitivity and improve prognosis of ESCC patients.	esophagus
Targeting CDH11 with celecoxib and derivatives to suppress esophageal squamous cell carcinoma proliferation and invasion.	BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with limited therapeutic options. Cadherin-11 (CDH11) has been implicated in tumor progression, but its role in ESCC remains unclear. METHODS: CDH11 expression was analyzed in ESCC tissues and cell lines. Functional assays (proliferation, migration, invasion) and xenograft models were employed to assess CDH11's role. Celecoxib and its derivative 2,5-dimethyl celecoxib (DMC) were evaluated as CDH11-targeted inhibitors. RESULTS: CDH11 was overexpressed in ESCC tissues and correlated with lymph node metastasis and poor prognosis. Knockdown of CDH11 suppressed ESCC proliferation and invasion (P < 0.05), while overexpression exacerbated these phenotypes. Celecoxib and DMC directly bound CDH11 and inhibited ESCC growth in vitro and in vivo (IC(50): 21.61-43.34 μM). Mechanistically, CDH11 knockdown attenuated JAK-STAT3 and AKT signaling. CONCLUSION: CDH11 is a novel therapeutic target in ESCC, and its inhibition by celecoxib/DMC offers a promising strategy for ESCC treatment.	esophagus
Trends in incidence and mortality of early-onset gastrointestinal cancers: a comprehensive study.	BACKGROUND: Early-Onset Gastrointestinal Cancers concerns tumors in people under 50. Accumulating evidence suggests a significant increase in the burden of colorectal cancer in young adults. We investigated the global burden and spatiotemporal trends of the 6 major gastrointestinal (GI) cancers, including colon and rectum cancer (CRC), esophageal cancer (EC), gallbladder and biliary tract cancer (GBTC), liver cancer (LC), pancreatic cancer (PC), and stomach cancer (SC). in young adults, based on cancer-specific incidence and mortality. METHODS: All data for 6 early-onset (EO) GI cancers were obtained from the Global Burden of Disease study. Age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and corresponding estimated annual percentage change (EAPC) were calculated to assess temporal trends from 1990 to 2019. RESULTS: The global number of cases and deaths from all EO-GI cancers has risen since 1990, reaching 539,750 and 309,200, respectively in 2019. ASIR and ASDR decreased for most EO-GI cancers (total, esophageal, gallbladder and biliary tract (GBTC), liver, and stomach cancers), while EO-pancreatic cancer showed an upward trend. EO colorectal cancer had increased incidence and stable mortality. However, these trends varied by sex, age, region, and economic status. Men had a higher burden of EO GI cancers (except GBTC), and older populations were more affected. Asia, particularly East Asia, had a significant burden, while the Americas showed the largest increase. Areas with Middle and High-middle sociodemographic indices had a relatively high burden of EO-GI cancers. CONCLUSIONS: The absolute burden of EO-GI cancers is rising worldwide, but the standardized burden has decreased, This indicates that we have made considerable progress in treatment and early detection.	esophagus
Ponicidin triggered ferroptosis in esophageal squamous cell carcinoma by suppressing the SLC7A11/Glutathione/GPX4 signalling axis.	BACKGROUND: Ponicidin, a diterpenoid derived from Rabdosia rubescens, exhibits potent antitumor activity. However, its mechanisms against esophageal squamous cell carcinoma (ESCC) remain obscure. This study aims to explore the effects of ponicidin against ESCC and reveal its molecular mechanisms. METHODS: The anti-ESCC effects of ponicidin were evaluated using CCK-8 assay, colony formation and transwell invasion assays. Cell cycle progression and mitochondrial membrane potential were analyzed using flow cytometry. Proteomics was applied to explore ponicidin's mechanisms. Ferroptosis induction was evaluated by quantifying reactive oxygen species, Fe(2+), malondialdehyde, glutathione, and lipid peroxidation levels. Docking and molecular dynamics simulations were conducted to identify the targets. siRNA was employed to validate target. The efficacy of ponicidin on tumorigenicity was explored in tumor xenograft mouse models, and its biosafety was evaluated via hemolysis assays, plasma ALT, AST, BUN, and CRE levels, as well as histopathological examinations. Western blot was used to analyze protein expression levels. RESULTS: Ponicidin inhibited ESCC cell proliferation, arrested cells in the G(2)/M phase, reduced mitochondrial membrane potential, and suppressed tumor growth without evident toxicity. Proteomics identified that ponicidin-induced ferroptosis is the predominant mechanism against ESCC. Ponicidin increased reactive oxygen species, malondialdehyde, Fe(2+), lipid peroxidation and glutathione depletion. Ferrostatin-1 pretreatment reduced lipid peroxidation, rescued PON induced inhibition of cell viability, and reversed the decreased expression of SLC7A11, GPX4 and GSR. Molecular docking revealed strong binding affinity of PON to GPX4 (-7.31±0.55 kcal/mol) and SLC7A11 (-8.19±0.37 kcal/mol). Molecular dynamics simulations confirmed stabilized complexes with total interaction energies of -23.43 ± 2.13 kcal/mol (GPX4-PON) and -31.42 ± 0.84 kcal/mol (SLC7A11-PON). siRNA-mediated knockdown of GPX4 and SLC7A11 reduced ESCC sensitivity to ponicidin-induced ferroptosis. CONCLUSION: This study provides the first evidence that ponicidin triggers ferroptosis in ESCC cells via suppression of the SLC7A11/glutathione/GPX4 signalling axis, offering actionable targets for ferroptosis-enhancing combination therapies.	esophagus
Trastuzumab Deruxtecan or Ramucirumab plus Paclitaxel in Gastric Cancer.	BACKGROUND: On the basis of phase 2 studies, trastuzumab deruxtecan was approved for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric cancer or gastroesophageal junction adenocarcinoma who had previously received trastuzumab-based therapy. Ramucirumab plus paclitaxel is also a standard second-line treatment option regardless of HER2 status. METHODS: We conducted an international, randomized, phase 3 trial comparing second-line trastuzumab deruxtecan at a dose of 6.4 mg per kilogram of body weight with ramucirumab plus paclitaxel in patients with HER2-positive metastatic gastric cancer or gastroesophageal junction adenocarcinoma confirmed on tumor biopsy conducted after the patient had progression while receiving trastuzumab-based therapy. The primary end point was overall survival. Secondary end points included progression-free survival, confirmed objective response (complete or partial response lasting ≥4 weeks), disease control, duration of response, and safety. RESULTS: Among 494 patients who had undergone randomization, overall survival was significantly longer with trastuzumab deruxtecan than with ramucirumab plus paclitaxel (median, 14.7 vs. 11.4 months; hazard ratio for death, 0.70; 95% confidence interval, 0.55 to 0.90; P = 0.004). Significant results were also seen with regard to progression-free survival (hazard ratio for disease progression or death, 0.74; 95% CI, 0.59 to 0.92) and confirmed objective response (in 44.3% of the patients in the trastuzumab deruxtecan group vs. 29.1% of those in the ramucirumab-paclitaxel group). The incidence of drug-related adverse events of any grade was 93.0% with trastuzumab deruxtecan and 91.4% with ramucirumab plus paclitaxel; the incidence of drug-related adverse events of grade 3 or higher was 50.0% and 54.1%, respectively. Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 13.9% of the patients who received trastuzumab deruxtecan (grade 1 or 2 in 33 patients and grade 3 in 1) and in 1.3% of those who received ramucirumab plus paclitaxel (grade 3 in 2 patients and grade 5 in 1). CONCLUSIONS: Trastuzumab deruxtecan led to significantly longer overall survival than ramucirumab plus paclitaxel among patients with HER2-positive metastatic gastric cancer or gastroesophageal junction adenocarcinoma. Adverse events were common in both groups. Events of interstitial lung disease or pneumonitis with trastuzumab deruxtecan, a known risk, were mainly low-grade. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Gastric04 ClinicalTrials.gov number, NCT04704934.).	esophagus
Clinical outcomes of pembrolizumab plus chemotherapy for postoperative recurrent esophageal squamous cell carcinoma.	BACKGROUND: Immunotherapy combined with chemotherapy has been the first-line treatment for metastatic or unresectable locally advanced esophageal cancer. However, postoperative recurrences have not been sufficiently investigated. We investigated the clinical outcomes of pembrolizumab plus cisplatin plus 5-fluorouracil (CF) therapy for postoperative recurrent esophageal squamous cell carcinoma. METHODS: We retrospectively analyzed 100 consecutive patients with postoperative recurrence and compared their treatment response and survival outcomes in response to pembrolizumab plus CF therapy and conventional CF therapy. RESULTS: Pembrolizumab plus CF therapy had higher response and objective response rates (41% vs. 27%, 77% vs. 57%, respectively) and prolonged progression-free survival (median 6.5 vs. 4.9 months, P = 0.011) and overall survival (not reached [NR] vs. 14.0 months, P = 0.087) compared to CF therapy. Early tumor shrinkage (ETS) ≧20% had a longer duration of response with pembrolizumab plus CF therapy compared with conventional CF therapy (NR vs. 10.2 months, P = 0.007). Conversely, the additional benefit of pembrolizumab in CF therapy was limited when ETS was <20% (4.0 vs. 3.4 months, P = 0.814). CF therapy was associated with worse survival outcomes for recurrences within 6 months post-surgery compared to those after 6 months. Pembrolizumab plus CF therapy provided comparable survival outcomes regardless of the timing of recurrence; however, it was less effective in combined positive score < 10 within the first 6 months. CONCLUSION: First-line pembrolizumab plus chemotherapy for postoperative recurrent esophageal cancer improved clinical outcomes compared to conventional CF therapy and can be expected to be one of the treatment options even in early postoperative recurrence.	esophagus
CircSLC22A3 inhibits the invasion and metastasis of ESCC via the miR-19b-3p/TRAK2 axis and by reducing the stability of m(6)A-modified ACSBG1 mRNA.	BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a major contributor to cancer-related deaths, driven by its invasive and metastatic nature. Circular RNAs (circRNAs) are increasingly recognized as regulators of cancer progression, primarily through miRNA sponging and interactions with RNA-binding proteins. Their dysregulation has been linked to the development of in various cancers. The present study aimed to investigate the potential involvement of circSLC22A3 in the pathogenesis of ESCC. METHODS: CircSLC22A3 expression in ESCC tissues and cells was analyzed using transcriptome sequencing and RT-qPCR. Its circular structure was validated through Sanger sequencing, agarose gel electrophoresis, RNase R digestion, and random priming assays. Subcellular localization was determined by nucleoplasmic separation and fluorescence in situ hybridization (FISH). Clinical correlations were assessed via tissue microarrays. Functional roles of circSLC22A3 in ESCC progression were investigated through in vitro and in vivo assays. Downstream miR-19b-3p and target gene TRAK2 were screened by bioinformatics analysis and RT-qPCR, with binding confirmed via luciferase reporter assays. RNA pulldown combined with RNA immunoprecipitation (RIP) identified IGF2BP1 as a circSLC22A3-interacting protein. RNA-seq and RT-qPCR revealed ACSBG1 as a key downstream effector. IGF2BP1-mediated m(6)A modification of ACSBG1 was mapped by MeRIP-seq and RIP, with mRNA stability assessed via Actinomycin D assay. ACSBG1 expression and biological function in ESCC were confirmed by immunohistochemistry, RT-qPCR, and functional assays. RESULTS: Significant downregulation of circSLC22A3 was observed in both ESCC tissues and cell lines. Overexpression of circSLC22A3 significantly reduced ESCC cells' migration and invasion capabilities. Mechanistic investigation revealed that circSLC22A3 played a pivotal role in the invasion and metastasis of esophageal cancer through distinct pathways. On one hand, circSLC22A3 functioned as a miR-19b-3p sponge to augment trafficking kinesin protein 2 (TRAK2) expression, while, on the other hand, circSLC22A3 formed a protein-RNA complex with IGF2BP1, resulting in the degradation of acyl-CoA synthetase bubblegum family member 1 (ACSBG1) mRNA through the recognition of m(6)A modification, thereby suppressing invasion and metastasis of ESCC. CONCLUSIONS: The present study identified circSLC22A3 as a new tumor suppressor that inhibited ESCC progression through both the circSLC22A3/ miR-19b-3p/ TRAK2 and circSLC22A3/ IGF2BP1/ ACSBG1 axes.	esophagus