crossing96/oncoscreening huggingface dataset:
The carcinogenesis of esophageal squamous cell cancer is positively regulated by USP13 through WISP1 deubiquitination.	The objective was to determine whether USP13 stabilizes WISP1 protein and contributes to tumorigenicity and metastasis in ESCC through the Wnt/CTNNB1 signaling pathway. ESCC cell lines (KYSE150 and TE10) were treated with the proteasome inhibitor MG-132, followed by siRNA screening of deubiquitinases (DUBs) to identify regulators of WISP1. Mass spectrometry, immunoprecipitation, and in vitro functional assays were conducted to explore the interaction between USP13 and WISP1 and to assess the effects of USP13 downregulation on cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and apoptosis. Additionally, in vivo experiments using mouse models were performed to evaluate the impact of USP13 knockdown on tumor growth and metastasis. USP13 was identified as a key regulator of WISP1, stabilizing its protein levels through deubiquitination. Downregulation of USP13 resulted in reduced WISP1 protein stability, decreased cell proliferation, migration, and EMT, and increased apoptosis in vitro. In vivo, USP13 knockdown significantly inhibited tumor growth and lung metastasis. WISP1 overexpression in USP13-knockdown cells partially rescued these phenotypes, confirming the functional role of the USP13/WISP1 axis. Furthermore, knockdown of USP13 or WISP1 impaired the activation of the Wnt/CTNNB1 signaling pathway and reduced immune checkpoint marker expression, indicating a mechanism by which USP13 promotes immune evasion in ESCC. USP13 stabilizes WISP1 through deubiquitination, enhancing ESCC progression by activating the Wnt/CTNNB1 pathway and promoting immune evasion, making USP13 a potential therapeutic target in ESCC.	esophagus
Prognostic role of lymph node regression in patients with esophageal cancer undergoing neoadjuvant therapy.	PURPOSE: To clarify the prognostic value of lymph node regression (LNR) status including the lymph node regression grade (LNRG) and N downstaging in patients with esophageal cancer receiving neoadjuvant therapy based on available evidence. METHODS: Several databases were searched up to 25 March 2024. The main outcomes included overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were combined. Subgroup analyses based on the neoadjuvant therapy and pathological type were also conducted. RESULTS: In total, 14 retrospective studies with 3,212 participants were included. Nine and five studies explored the relationship between LNRG and N downstaging and survival, respectively. Pooled results indicated that complete LNR predicted significantly improved OS (HR = 0.47, 95% CI: 0.41-0.55, P < 0.001) and DFS (HR = 0.42, 95% CI: 0.32-0.55, P < 0.001) and subgroup analysis based on neoadjuvant therapy and pathological type manifested similar results. Besides, N downstaging was also significantly related to improved OS (HR = 0.40, 95% CI: 0.21-0.77, P = 0.006) and CSS (HR = 0.27, 95% CI: 0.12-0.60, P < 0.001). CONCLUSION: LNR could serve as a novel and reliable prognostic factor in patients with esophageal cancer receiving neoadjuvant therapy and complete LNR and N downstaging predict better survival.	esophagus
S-1-based concurrent chemoradiotherapy plus nimotuzumab in patients with locally advanced esophageal squamous cell carcinoma who failed neoadjuvant therapy: a real-world prospective study.	PURPOSE: This prospective study in a real-world setting investigated the feasibility and safety of S-1 plus nimotuzumab (S-1-Nimo) based concurrent chemoradiotherapy (CCRT) in locally advanced esophageal squamous cell carcinoma (LA-ESCC) patients who failed to neoadjuvant chemotherapy or chemoimmunotherapy. METHODS: LA-ESCC patients who failed to converse to resectable disease after neoadjuvant chemotherapy or chemoimmunotherapy were enrolled to receive the 4-week S-1-Nimo regimen of radiotherapy (40 Gy in 20 fractions, 5 days per week), S-1 chemotherapy, and nimotuzumab. Then, after surgical assessments, patients evaluated as resectable disease received surgery; patients with unresectable disease continued to receive definitive radiotherapy (50-60 Gy in 25-30 fractions, 5 days per week) concurrently with S-1-Nimo. The primary endpoint was event-free survival (EFS). RESULTS: Sixty-four patients were enrolled and evaluated. The median follow-up time was 23.2 months. Median EFS was 9.6 (95% confidence interval [CI], 7.1-14.0) months, with an estimated 2-year EFS rate of 24.2%. The median overall survival (OS) and the estimated OS rate at 2 years were 13.4 (95% CI, 10.3-17.5) months and 31.2%, respectively. Twelve underwent surgery, with a surgical conversion rate of 18.8% and an R0 resection rate of 100.0%. Subgroup analysis identified the significantly prolonged EFS and OS in patients who experienced radical surgery (median EFS, not reached vs. 8.7 months; p = .0117. median OS, 24.9 vs. 10.6 months; p = .0205) as compared to those treated with CCRT. Of 64 patients, grade 3 adverse events mainly included radiation esophagitis (4.7%), anemia (1.6%), and thrombocytopenia (1.6%). CONCLUSION: The study demonstrated the reasonable efficacy and promising safety of the S-1-Nimo-based CCRT in LA-ESCC patients with failure to neoadjuvant chemotherapy or chemoimmunotherapy.	esophagus
[Recurrent Esophageal Cancer Showing Good Response to Nivolumab in a Super-Elderly Patient-A Case Report].	A 91-year-old man with thoracic esophageal cancer(pT3N1M0, pStage Ⅲ)and gastric cancer(pT1b2N0M0, pStage ⅠA)underwent esophagectomy. Three years and 4 months postoperatively, chest computed tomography revealed a mass shadow near the aortic arch. Upper gastrointestinal endoscopy revealed a submucosal tumor-like lesion on the left wall of the gastric tube, which was identified as recurrent esophageal cancer. The patient and his family strongly requested nivolumab administration and initiated treatment. The tumor shrank remarkably after 6 months of nivolumab therapy. Although an immune-related adverse event(irAE)was observed, no other adverse events occurred. After 1 year of administration, the tumor did not increase, and remained under control. We suggest that nivolumab therapy is an effective regimen for older patients with recurrent or inoperable esophageal cancer that is difficult to treat with conventional anticancer drugs, provided that strong irAEs do not occur.	esophagus
[Feasibility of FP Therapy in Outpatient Setting for Inoperable Recurrent Esophageal Cancer].	With the emergence of immune checkpoint inhibitors(ICIs)in recent years, the treatment outcomes for unresectable recurrent esophageal cancer have improved markedly. In 5-FU+cisplatin(FP)first-line therapy, 5-FU administration takes 5 days and generally requires hospitalization. However, frequent hospitalization for treatment is a crucial issue that must be resolved in terms of time investment and optimal use of hospital resources. Here, we evaluated the safety and potential adverse effects of the administration of FP therapy in an outpatient setting. After central venous ports were placed in 5 patients, cisplatin was administered using a short hydration method and 5-FU was infused for 120 hours using an infusion pump. No crucial adverse events or major pump-related problems occurred, suggesting the feasibility of this treatment in an outpatient setting. However, the duration of 5-FU administration via the pump varied more than the expected deviation (10%, 12 hours), indicating that the issues require further consideration.	esophagus
Achievements of perioperative assist team medical care in esophageal cancer surgery, Tokushima University Hospital.	BACKGROUND: Radical esophagectomy is highly invasive and associated with many postoperative complications. A decline in postoperative QOL is a serious issue for patients, and comprehensive perioperative management through multidisciplinary cooperation is necessary. Our institution has established a perioperative assist team (OPERA) to address this need since 2017. METHODS: This study included 109 patients with esophageal cancer who underwent neoadjuvant chemotherapy and esophagectomy from 2009 to 2018. O group, means OPERA intervention group, included 57 patients, and N group, means Non-OPERA intervention group, included 52 patients. The effects of the OPERA intervention on reducing chemotherapy-related adverse events and improving postoperative outcomes were retrospectively investigated. RESULTS: The OPERA intervention significantly reduced the incidence of chemotherapy-related adverse events (P=0.002). In particular, anorexia and diarrhea, febrile neutropenia were significantly reduced (P<0.001, P=0.002, P=0.025, respectively). Postoperatively, the start date of walking was significantly earlier (P<0.001), the incidence of pneumonia was lower (P=0.022). At the time of postoperative discharge, N group was significantly greater weight loss compared to O group (P=0.002). The 5-year survival rate was longer in O group (P=0.003). CONCLUSION: The OPERA intervention reduced the incidence of chemotherapy-related adverse events and postoperative complications and helped improved prognosis. J. Med. Invest. 71 : 279-285, August, 2024.	esophagus
Dysregulated inclusion of BOLA3 exon 3 promoted by HNRNPC accelerates the progression of esophageal squamous cell carcinoma.	Dysregulated RNA splicing events produce transcripts that facilitate esophageal squamous cell carcinoma (ESCC) progression, but how this splicing process is abnormally regulated remains elusive. Here, we unveiled a novel alternative splicing axis of BOLA3 transcripts and its regulator HNRNPC in ESCC. The long-form BOLA3 (BOLA3-L) containing exon 3 exhibited high expression levels in ESCC and was associated with poor prognosis. Functional assays demonstrated the protumorigenic function of BOLA3-L in ESCC cells. Additionally, HNRNPC bound to BOLA3 mRNA and promoted BOLA3 exon 3 inclusion forming BOLA3-L. High HNRNPC expression was positively correlated with the presence of BOLA3-L and associated with an unfavorable prognosis. HNRNPC knockdown effectively suppressed the malignant biological behavior of ESCC cells, which were significantly rescued by BOLA3-L overexpression. Moreover, BOLA3-L played a significant role in mitochondrial structural and functional stability. E2F7 acted as a key transcription factor that promoted the upregulation of HNRNPC and inclusion of BOLA3 exon 3. Our findings provided novel insights into how alternative splicing contributes to ESCC progression.	esophagus
Report from the 25th Annual Western Canadian Gastrointestinal Cancer Consensus Conference on Gastric and Gastroesophageal Cancers, Winnipeg, Manitoba, 26-27 October 2023.	The 25th Annual Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held in Winnipeg, Manitoba, on 26-27 October 2023. The WCGCCC is an interactive multidisciplinary conference that was attended by healthcare professionals from across Western Canada (British Columbia, Alberta, and Manitoba) who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; oncology nurses; pharmacists; and a family physician in oncology (FPO) participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of gastroesophageal cancers.	esophagus
AREG Upregulation in Cancer Cells via Direct Interaction with Cancer-Associated Fibroblasts Promotes Esophageal Squamous Cell Carcinoma Progression Through EGFR-Erk/p38 MAPK Signaling.	Cancer-associated fibroblasts (CAFs) are a key component of the tumor microenvironment and significantly contribute to the progression of various cancers, including esophageal squamous cell carcinoma (ESCC). Our previous study established a direct co-culture system of human bone marrow-derived mesenchymal stem cells (progenitors of CAFs) and ESCC cell lines, which facilitates the generation of CAF-like cells and enhances malignancy in ESCC cells. In this study, we further elucidated the mechanism by which CAFs promote ESCC progression using cDNA microarray analysis of monocultured ESCC cells and those co-cultured with CAFs. We observed an increase in the expression and secretion of amphiregulin (AREG) and the expression and phosphorylation of its receptor EGFR in co-cultured ESCC cells. Moreover, AREG treatment of ESCC cells enhanced their survival and migration via the EGFR-Erk/p38 MAPK signaling pathway. Immunohistochemical analysis of human ESCC tissues showed a positive correlation between the intensity of AREG expression at the tumor-invasive front and the expression level of the CAF marker FAP. Bioinformatics analysis confirmed significant upregulation of AREG in ESCC compared with normal tissues. These findings suggest that AREG plays a crucial role in CAF-mediated ESCC progression and could be a novel therapeutic target for ESCC.	esophagus
HLX07 alone or combined with serplulimab, cisplatin and 5-fluorouracil for advanced esophageal squamous cell carcinoma: A phase 2 study.	BACKGROUND: The combination of anti-PD-1 antibody serplulimab and chemotherapy is considered standard first-line therapy for advanced esophageal squamous cell carcinoma (ESCC), but few later-line treatments are available. Here we evaluated the therapeutic efficacy of the recombinant, humanized anti-EGFR antibody HLX07 when used alone or together with serplulimab and chemotherapy against advanced ESCC. METHODS: This open-label, non-randomized, two-cohort, phase 2 trial involved patients 18-75 years old with histologically or cytologically confirmed locally advanced, unresectable, or metastatic ESCC, and an Eastern Cooperative Oncology Group performance status of 0-1. Patients who had failed first-line immuno-chemotherapy or at least two lines of other systemic therapy received HLX07 monotherapy intravenously at a dose of 1,000 mg once every 2 weeks (Q2W). Patients with no prior systemic therapy received HLX07 (1,000 mg, day 1) and serplulimab (200 mg, day 1) intravenously Q2W for up to 2 years, concurrently with cisplatin (50 mg/m(2), day 1) for up to 8 cycles and 5-fluorouracil (1,200 mg/m(2), days 1-2) for up to 12 cycles intravenously Q2W. The primary endpoints were progression-free survival (PFS) and objective response rate (ORR). RESULTS: Overall, 50 patients were enrolled. In the HLX07 monotherapy group, ORR was 15.0% (3/20), and the median PFS was 1.5 months (95% confidence interval [CI], 1.3 to 3.7). The median duration of response was not reached, and the rate of patients showing an objective response lasting at least 6 months was 66.7% (95% CI, 5.4 to 94.5). Two (10.0%, 2/20) patients experienced grade 3-4 treatment-related adverse events (TRAEs), including hypomagnesemia, hypocalcemia, and fatigue. No patient experienced grade 5 TRAEs. In the HLX07 combination group, the ORR was 60.0% (18/30), and the median PFS was 7.8 months (95% CI, 3.3 to 9.1). Fourteen (46.7%, 14/30) patients experienced grade 3-4 TRAEs, and one (3.3%, 1/30) patient died due to serplulimab-related pneumonitis. CONCLUSIONS: HLX07 monotherapy and its combination with serplulimab and chemotherapy showed manageable toxicity and promising antitumor activity in patients with recurrent or metastatic ESCC. Randomized controlled trials are warranted to further establish the safety and efficacy of HLX07 against ESCC. TRIAL REGISTRATION: This trial was registered at Clinicaltrials.gov (NCT05221658).	esophagus
Establishment and validation of the prognostic risk model based on the anoikis-related genes in esophageal squamous cell carcinoma.	BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a malignant condition in humans. Anoikis-related genes (ARGs) are crucial to cancer progression. Therefore, more studies on the relationship between ARGs and ESCC are warranted. METHODS: The study acquired ESCC-related transcriptome data from TCGA. Differentially expressed ARGs (DE-ARGs) were obtained by differential analysis and candidates were filtered out by survival analysis. Prognostic genes were determined by Cox and LASSO regression. A risk model was constructed based on prognostic gene expressions. An immune infiltration study was done to explain how these genes contribute to ESCC development. The IC50 test was adopted to assess the clinical response of chemotherapy drugs. Single cell analysis was performed on the GSE145370 dataset. Moreover, the prognostic gene expressions were detected by qRT-PCR. RESULTS: 53 DE-ARGs were screened and four candidate genes including PBK, LAMC2, TNFSF10 and KL were obtained. Cox and LASSO regression identified the two prognostic genes, TNFSF10 and PBK. Immuno-infiltration analysis revealed positive associations of PBK with Macrophages M0 cells, and TNFSF10 with Macrophages M1 cells. The IC50 values of predicted drugs, in the case of Tozasertib 1096 and WIKI4 1940, were significantly variant between risk groups. Single cell analysis revealed that TNFSF10 and PBK levels were higher in epithelial cells than in other cells. The prognostic genes expression results by qRT-PCR were compatible with the dataset analysis. CONCLUSION: The study established an ARG prognosis model of ESCC. It provided a reference for the research of ARGs in ESCC.	esophagus
Evaluation of the robustness of randomized controlled trials for the treatment modalities of esophageal cancer using the fragility index - a systematic review.	BACKGROUND: Esophageal cancer remains a significant global health challenge. Several treatment modalities were explored in randomized controlled trials (RCTs) in recent decades. This study evaluates the robustness of RCTs focusing on esophageal cancer treatment using the fragility index (FI) and reverse fragility index (RFI). METHODS: A systematic review of RCTs studying different treatment modalities for esophageal cancer from 2000 to 2023 was conducted. The FI and RFI were utilized to gauge the robustness of statistically significant and non-significant outcomes, respectively. The FI represents the minimal number of patient outcomes that would need to alter to overturn a trial's statistical significance, while RFI indicates the minimal changes required to achieve significance in non-significant results. RESULTS: Out of 4028 studies retrieved, 21 RCTs were included for final analysis. The studies spanned 2001 to 2023 with a mean followup of 66 months (range, 29-108 months) and median number of patients of 194 (range, 45-802). The most common treatment modalities examined in these studies were neoadjuvant chemoradiotherapy (n = 7, 33.3%), neoadjuvant chemotherapy (n = 4, 19.0%), and neoadjuvant immunotherapy (n = 2, 9.5%). Only 5 studies (23.8%) had a statistically significant primary outcome result with a median FI of 6 (IQR, 2.5-8.5). Non-significant primary outcomes were seen in 16 studies (76.2%) with a median RFI of 4 (IQR 1-11) and lost to followup of 0 (IQR 0-4). In the study with the highest FI (10), the FI was lower than the number of patients lost to followup (13). CONCLUSION: Our findings demonstrate that most RCTs on esophageal cancer treatments did not report significant primary outcomes. The few studies that reported significant results had a low fragility index, suggesting a vulnerability in their findings.	esophagus
Evolving Treatment Landscape for Advanced Esophageal and Gastroesophageal Junction Adenocarcinoma.	PURPOSE OF REVIEW: This review highlights advances and recent changes in the treatment paradigm for advanced esophageal adenocarcinoma (EAC) and gastroesophageal junction adenocarcinoma (GEJAC). RECENT FINDINGS: Chemotherapy remains the backbone of treatment for advanced EAC/GEJAC. New targets/agents include immunotherapy, HER-2, claudin18.2, and FGFR2b, with various mechanisms (CAR-T, bispecific mAB, ADCs) altering the treatment landscape against these targets. The approaches to these targets may act together, in sequence, and even synergistically to improve outcomes. Herein, we review the state of the field, including highlighting ongoing clinical trials and additional emerging agents and approaches.	esophagus
FOXP3+/CD8+ ratio associated with aggressive behavior in RUNX3-methylated diffuse esophagogastric junction tumor.	The tumor immune microenvironment is increasingly becoming a key consideration in developing treatment regimens for aggressive cancers, with evidence that regulatory T cells (Tregs) attenuate the antitumor response by interrupting cytotoxic T cells (CD8+). Here, we hypothesized the prognostic relevance of the proportions of Tregs (marked by forkhead box protein 3 [FOXP3]) and CD8+ cells in diffuse, non-Epstein-Barr virus (EBV)/non-microsatellite instability (MSI)-high gastroesophageal adenocarcinomas (GEAs), which are clinically characterized as more aggressive, immunologically inactive tumors as compared with their intestinal counterparts. Cell-count ratios of FOXP3+/CD8+ expression were calculated at the intratumoral region and invasive margin discretely on digital images from 303 chemo-naive non-EBV/non-MSI-high esophagogastric junction (EGJ) adenocarcinomas. A significant modifying prognostic effect of tumor histology was observed between 5-year EGJ cancer-specific survival and the FOXP3+/CD8+ ratio at the invasive margin in pStage I-III tumors (p for interaction = 0.022; hazard ratio [HR] = 8.47 and 95% confidence interval [CI], 2.04-35.19 for high ratio [vs. low] for diffuse; HR = 1.57 and 95% CI, 0.88-2.83 for high ratio [vs. low] for intestinal). A high FOXP3+/CD8+ ratio at the invasive margin was associated with RUNX3 methylation (p = 0.035) and poor prognosis in RUNX3-methylated diffuse histological subtype (5-year EGJ cancer-specific survival, 52.3% for high and 100% for low, p = 0.015). Multiomics data from The Cancer Genome Atlas linked CCL28 with RUNX3-suppressed diffuse histological subtypes of non-EBV/non-MSI-high GEA. Our data suggest that a high FOXP3+/CD8+ ratio at the invasive margin might indicate tumor immune escape via CCL28, particularly in the RUNX3-methylated diffuse histological subtype.	esophagus
Survival comparison between open and thoracoscopic esophagectomy for node-negative esophageal squamous cell cancer: an ambispective cohort study.	BACKGROUND: It is controversial whether there is a survival difference between open esophagectomy (OE) and thoracoscopic esophagectomy (TE) for esophageal cancer (EC). Therefore, this study aimed to compare the differences in survival and safety between two surgical approaches in patients with node-negative esophageal squamous cell carcinoma (ESCC). METHODS: This ambispective cohort study included 1104 patients with node-negative ESCC who received OE or TE treatment at a Grate-A tertiary hospital in Henan Province between January 2015 and December 2016. The primary endpoint was 5-year overall survival (OS) and disease-free survival (DFS), and the secondary endpoint was surgical safety. Multivariable Cox regression analysis was used to analyze the effect of surgical approaches on OS and DFS, and propensity score matching (PSM) was performed to match confounding factors between two groups. RESULTS: Patients were followed up ranged from 1.03 to 91.60 months, with a median follow-up time of 67.37 months. Kaplan-Meier survival analysis showed statistically significant differences between OE and TE in OS (70.05% vs 83.73%, P < 0.001) and DFS (67.15% vs 77.76%, P < 0.001). Furthermore, multivariate Cox regression analysis also demonstrated significant differences in long-term survival between the two groups (OS, HR (95% CI): 0.54 (0.41, 0.70); DFS, HR (95% CI): 0.68 (0.54, 0.86)). TE was associated with a reduction in intraoperative bleeding (median: 100 ml vs. 200 ml, P < 0.001), and an increase in the number of lymph nodes dissection (median: 23 vs. 28, P < 0.001). Similar results were found after PSM. CONCLUSION: In a selected cohort of patients with node-negative ESCC, TE surgical treatment was safer and had better long-term survival outcomes compared to OE. This provided corresponding clinical guidance to enhance survival benefits for patients. In the future, we hope to further explore the reasons for TE achieving higher survival rates.	esophagus