crossing96/oncoscreening huggingface dataset:
Oridonin Induces Apoptosis in Esophageal Squamous Cell Carcinoma by Inhibiting Cytoskeletal Protein LASP1 and PDLIM1.	Esophageal squamous cell carcinoma is a severe malignancy for its high mortality and poor prognosis. Mainstay chemotherapies cause serious side effects for their ways of inducing cell death. Oridonin is the main bioactive constituent from natural plants that has anticancer ability and weak side effects. The proteomics method is efficient to understand the anticancer mechanism. However, proteins identified by proteomics aimed at understanding oridonin's anticancer mechanism is seldom overlapped by different groups. This study used proteomics based on two-dimensional electrophoresis sodium dodecyl sulfate-polyacrylamide gel electrophoresis (2-DE SDS-PAGE) integrated with mass spectrometry and Gene Set Enrichment Analysis (GSEA) to understand the anticancer mechanism of oridonin on esophageal squamous cell carcinoma (ESCC). The results showed that oridonin induced ESCC cell death via apoptosis by decreasing the protein expression of LASP1 and PDLIM1.	esophagus
DNA methylation biomarkers accurately detect esophageal cancer prior and post neoadjuvant chemoradiation.	BACKGROUND: Esophageal cancer (ECa) is associated with high mortality, mostly due to late diagnosis, precluding curativeintent surgery. Hence, neoadjuvant chemoradiation (ChRT) is recommended in most patients regardless of histological subtype. A proportion of these patients, however, achieve complete disease remission and might be spared of radical surgery. The lack of reliable, minimally invasive biomarkers able to detect post-ChRT disease persistence is, nonetheless, a major drawback. We have previously shown that miRNA promotor methylation enables accurate cancer detection in tissues and liquid biopsies but has been seldom explored in ECa patients. AIMS: Herein, we sought to unveil and validate novel candidate biomarkers able to detect ECa prior and post ChRT. MATERIALS AND METHODS: Promoter methylation of miR129-2, miR124-3 and ZNF569 was assessed, using quantitative methylation-specific PCR (qMSP), in tissue samples from normal esophagus, treatment-naïve and post-ChRT ECa, as well as in liquid biopsies from ECa patients. RESULTS: All genes disclosed significantly different promoter methylation levels between ECa and normal esophagus, accurately detecting post-ChRT disease, especially for adenocarcinoma. Remarkably, miR129-2(me) /ZNF569(me) methylation panel identified ECa in liquid samples with 53% sensitivity and 87% specificity. DISCUSSION: MiR129-2(me) , miR124-3(me) and ZNF569(me) accurately discriminate ECa, either pre- or post-ChRT, from normal tissue, enabling ECa detection. Furthermore, circulalting methylation-based biomarkers are promising minimally invasive tools to detect post-ChRT residual ECa. CONCLUSION: Overall, our results encourage the use of miRNA methylation biomarkers as accurate ECa detection tools as a novel approach for ChRT response monitoring.	esophagus
BACH1-induced ferroptosis drives lymphatic metastasis by repressing the biosynthesis of monounsaturated fatty acids.	Esophageal squamous cell carcinoma (ESCC) is one of the fatal malignancies worldwide. It has an increased propensity to metastasize via lymphogenous routes in an early stage. The prognosis of patients with lymph node metastases (LNM) is often worse than that of patients without metastases. Although several factors have been found to influence metastasis, the mechanisms of preference for specific metastatic routes remain poorly understood. Herein, we provide evidence that the intrinsic hypersensitivity of tumor cells to ferroptosis may proactively drive lymphatic metastasis. Serum autoantibodies associated with LNM of early ESCC were screened using a whole-proteome protein array containing 19 394 human recombinant proteins, and an anti-BACH1 autoantibody was first identified. Pan-cancer analysis of ferroptosis-related genes with preferential lymphatic metastasis and preferential hematogenous metastasis based on The Cancer Genome Atlas data was performed. Only BACH1 showed significant overexpression in tumors with preferential lymphatic metastasis, whereas it was downregulated in most tumors with preferential nonlymphatic metastasis. In addition, it was found that the serum levels of autoantibodies against BACH1 were elevated in early-stage patients with LNM. Interestingly, BACH1 overexpression and ferroptosis induction promoted LNM but inhibited hematogenous metastasis in mouse models. Transcriptomic and lipidomic analyses found that BACH1 repressed SCD1-mediated biosynthesis of monounsaturated fatty acids, especially oleic acid (OA). OA significantly attenuated the ferroptotic phenotypes and reversed the metastatic properties of BACH1-overexpressing cells. OA addition significantly rescued the ferroptotic phenotypes and reversed the metastatic properties of BACH1-overexpressing cells. Importantly, the concentration gradient of OA between primary lesions and the lymph resulted in the chemoattraction of tumor cells to promote invasion, thus facilitating lymphatic metastasis. BACH1-induced ferroptosis drives lymphatic metastasis via the BACH1-SCD1-OA axis. More importantly, this study confirms that ferroptosis is a double-edged sword in tumorigenesis and tumor progression. The clinical application of ferroptosis-associated agents requires a great caution.	esophagus
Trifluridine/Tipiracil in the Real-World Management of Metastatic Gastric and Gastroesophageal Junction Cancers in Canada.	BACKGROUND: Gastric cancer mortality remains among the highest of all cancers. Trifluridine/tipiracil (FTD/TPI) represents Canada's first standard-of-care, third-line, systemic therapy for metastatic gastric/gastroesophageal cancer. We characterized real-world treatment patterns in patients enrolled to receive FTD/TPI through Taiho Pharma Canada's Patient Support Program. METHODS: Demographic and clinical information were collected from November 2019 to November 2021 for adult patients with refractory metastatic gastric/gastroesophageal cancer throughout Canada. We examined all variables using descriptive statistics and performed survival and association analyses. RESULTS: 162 patients enrolled to receive FTD/TPI with a median age of 65 years, 12 of whom had HER2 positive disease. Among 123 patients who started FTD/TPI, median follow-up was 3.1 months and median progression-free survival (PFS) was 3.5 months (95% CI 3.2-4.0). Among 121 patients who discontinued FTD/TPI, median treatment duration was 2.39 cycles (IQR 1.14-3.86). A total of 52% discontinued treatment due to disease progression, and 27% had a dose reduction or delay. On multivariable logistic regression, prior FOLFIRI was a statistically significant predictor of treatment modification. CONCLUSIONS: Through the Patient Support Program, FTD/TPI is an actively utilized treatment option in heavily pretreated metastatic gastric/gastroesophageal cancer, despite its recent introduction. With longer-than-expected treatment duration and PFS, FTD/TPI likely addresses an important unmet need for effective and tolerable therapies in this setting.	esophagus
Identification of Differentially Expressed Genes Related to the Lipid Metabolism of Esophageal Squamous Cell Carcinoma by Integrated Bioinformatics Analysis.	Purpose: In recent years, lipid metabolism has been reprogrammed to meet the energy and substrate needs of tumorigenesis and development and is a potential new target for cancer treatment. However, the regulatory mechanism of lipid metabolism in esophageal squamous cell carcinoma is not well understood. Methods: We first downloaded the esophageal squamous cell carcinoma (ESCC) gene dataset in the GEO and TCGA databases and analyzed the central differentially expressed genes (DEGs) of ESCC through bioinformatics. Afterwards, the GSEA method was used to analyze the lipid metabolism-related pathway of the central gene in the pathological process of ESCC, and it was determined that the central gene OIP5 was significantly related to the fatty acid metabolism pathway. Our heatmap also revealed that the enrichment of the ACSL family in ESCC tissues was more pronounced than in normal tissues. We hypothesized that OIP5 can regulate the fatty acid metabolism process in ESCC cells and affect the tumorigenic ability of ESCC. Further statistical analysis and experiment were conducted to determine the lipid metabolism-related gene, OIP5′s, expression pattern and clinical significance in ESCC, analyze the effect of OIP5 expression on fatty acid metabolism-related enzymes in ESCC, revealing the specific mechanism of OIP5 that promotes ESCC development. Conclusions: Our study established a correlation between OIP5 expression and clinicopathological factors (tumor size, T stage, N stage, and clinical grade) in esophageal squamous cell carcinoma (p < 0.05). We have also experimentally demonstrated that OIP5 regulates ESCC fatty acid metabolism by influencing the expression of the key enzyme ACSL1 in lipid metabolism.	esophagus
Malignant Neoplasms of the Gastrointestinal Tract After Blood or Marrow Transplant.	IMPORTANCE: Survivors of blood or marrow transplant (BMT) are at increased risk of subsequent malignant neoplasms (SMNs). Cancers of the gastrointestinal (GI) system are of special interest because their clinical behavior is often aggressive, necessitating early detection by increasing awareness of high-risk populations. OBJECTIVE: To describe the risk of SMNs in the GI tract after BMT. DESIGN, SETTING, AND PARTICIPANTS: A cohort study of 6710 individuals who lived at least 2 years after BMT performed between January 1, 1974, and December 31, 2014, at City of Hope, University of Minnesota, or University of Alabama at Birmingham. End of follow-up was March 23, 2020. Data analysis was performed between September 1, 2022, and September 30, 2022. EXPOSURES: Demographic and clinical factors; therapeutic exposures before or as part of BMT. MAIN OUTCOMES AND MEASURES: Development of SMNs in the GI tract after BMT. Participants self-reported SMNs in the GI tract; these were confirmed with pathology reports, medical records, or both. For deceased patients, death records were used. Standardized incidence ratios determined excess risk of SMNs in the GI tract compared with that of the general population. Fine-Gray proportional subdistribution hazard models assessed the association between risk factors and SMNs in the GI tract. RESULTS: The cohort of 6710 individuals included 3444 (51.3%) autologous and 3266 (48.7%) allogeneic BMT recipients. A total of 3917 individuals (58.4%) were male, and the median age at BMT was 46 years (range, 0-78 years). After 62 479 person-years of follow-up, 148 patients developed SMNs in the GI tract. The standardized incidence ratios for developing specific SMNs ranged from 2.1 for colorectal cancer (95% CI, 1.6-2.8; P < .001) to 7.8 for esophageal cancer (95% CI, 5.0-11.6; P < .001). Exposure to cytarabine for conditioning (subdistribution hazard ratio [SHR], 3.1; 95% CI, 1.5-6.6) was associated with subsequent colorectal cancer. Compared with autologous BMT recipients, allogeneic BMT recipients with chronic graft-vs-host disease were at increased risk for esophageal cancer (SHR, 9.9; 95% CI, 3.2-30.5). Conditioning with etoposide (SHR, 2.0; 95% CI, 1.1-3.5) and pre-BMT anthracycline exposure (SHR, 5.4; 95% CI, 1.3-23.4) were associated with an increased risk of liver cancer compared with no exposure to the respective agents. CONCLUSIONS AND RELEVANCE: The findings of this cohort study are relevant for oncologists and nononcologists who care for the growing number of survivors of transplant. Awareness of subgroups of survivors of BMT at high risk for specific types of SMNs in the GI tract may influence recommendations regarding modifiable risk factors, as well as individualized screening.	esophagus
Outcomes of Intraoperative Pyloric Drainage on Delayed Gastric Emptying Following Esophagectomy: A Systematic Review and Meta-analysis.	BACKGROUND: Intraoperative pyloric drainage in esophagectomy may reduce delayed gastric emptying (DGE) but is associated with risk of biliary reflux and other complications. Existing evidence is heterogenous. Hence, this meta-analysis aims to compare outcomes of intraoperative pyloric drainage versus no intervention in patients undergoing esophagectomy. METHODS: PubMed/MEDLINE, Embase, Web of Science, and the Cochrane were searched from inception up to July 2022. Exclusion criteria were lack of objective evidence (e.g., symptoms of nausea or vomiting) of DGE. The primary outcome was incidence of DGE. Secondary outcomes were incidence of pulmonary complications, bile reflux, anastomotic leak, operative time, and mortality. RESULTS: There were nine studies including 1164 patients (pyloric drainage n = 656, no intervention n = 508). Intraoperative pyloric drainage included pyloroplasty (n = 166 (25.3%)), pyloromyotomy (n = 214 (32.6%)), botulinum toxin injection (n = 168 (25.6%)), and pyloric dilatation (n = 108 (16.5%)). Pyloric drainage is associated with reduced DGE (odds ratio (OR): 0.54, 95% confidence interval (CI): 0.39-0.74, I(2) = 50%). There was no significant difference in incidence of pulmonary complications (OR: 0.74, 95% CI: 0.51-1.08; I(2) = 0%), biliary reflux (OR: 1.43, 95% CI: 0.80-2.54, I(2) = 0%), anastomotic leak (OR: 0.79, 95% CI: 0.48-1.29; I(2) = 0%), operative time (MD: + 22.16 min, 95% CI: - 13.27-57.59 min; I(2) = 76%), and mortality (OR: 1.13, 95% CI: 0.48-2.64, I(2) = 0%) between the pyloric drainage and no intervention groups. CONCLUSIONS: Pyloric drainage in esophagectomy reduces DGE but has similar post-operative outcomes. Further prospective studies should be carried out to compare various pyloric drainage techniques and its use in esophagectomy, especially minimally-invasive esophagectomy.	esophagus
Endoscopic mucosal ischemic index for predicting anastomotic complications after esophagectomy: a prospective cohort study.	BACKGROUND: Postoperative complications related to gastric conduit reconstruction are still common issues after McKeown esophagectomy. A novel endoscopic mucosal ischemic index is desired to predict anastomotic complications after McKeown esophagectomy. AIMS AND METHODS: The purpose of this study was to prospectively evaluate the safety and efficacy of endoscopic examinations of the anastomotic region in the acute period after esophagectomy. Endoscopic examinations were performed on postoperative days (PODs) 1 and 8. The severity of ischemia was prospectively validated according to the endoscopic mucosal ischemic index (EMII). RESULTS: A total of 58 patients were included after evaluating the safety and feasibility of the endoscopic examination on POD 1 in 10 patients. Anastomotic leakage occurred in 6 patients. Stricture occurred in 13 patients. A greater than 67% circumference and lesion length greater than 20 mm of anastomotic ischemic area (AIA) on POD 1 were associated with developing anastomotic leakage after esophagectomy (OR: 14.5; 95% CI: 1.8-306.5; P = 0.03, OR: 19.4; 95% CI: 1.7-536.8; P = 0.03). More than 67% circumferential ischemic mucosa and ischemic mucosal lengths greater than 20 mm of AIA on POD 1 were associated with developing anastomotic strictures after esophagectomy (OR: 6.4; 95% CI: 1.4-31.7; P = 0.02, OR: 5.9; 95% CI: 1.2-33.1; P = 0.03). Patients with either more than 67% circumferential ischemic mucosa or ischemic mucosal lengths greater than 20 mm of AIA on POD 1 were defined as EMII-positive patients. The sensitivity, specificity, and positive and negative predictive values of EMII positivity on POD 1 for leakage were 100%, 78.8%, 35.3%, and 100%, respectively. The sensitivity, specificity, and positive and negative predictive values of the EMII positivity on POD 1 for strictures were 69.2%, 82.2%, 52.9%, and 90.2%, respectively. CONCLUSIONS: The application of an endoscopic classification system to mucosal ischemia after McKeown esophagectomy is both appropriate and satisfactory in predicting anastomotic complications. TRIAL REGISTRATION: Clinical Trial.gov Registry, ID: NCT02937389, Registration date: Oct 17, 2015.	esophagus
NR2F1-AS1: A Functional Long Noncoding RNA in Tumorigenesis.	"BACKGROUND: NR2F1-AS1 is a long non-coding RNA (lnc RNA) that is involved in different biological processes. It plays an integral role in the pathophysiology of human diseases, especially tumorigenesis and progression. Therefore, it may be a promising target for numerous tumor biotherapeutics. The current review study aimed to show the pathophysiological activities and processes of RNA NR2F1-AS1 in cancer cells. METHODS: The contents of the present review were based on information obtained from PubMed. In the data search, ""NR2F1-AS1"" was chosen as the first keyword, whereas ""cancer"" was chosen as the second keyword. This review selected and summarized studies published between 2019-2021, concerning the biological functions and mechanisms of NR2F1-AS1 in the development of tumorigenesis. RESULTS: It was found that NR2F1-AS1 regulates a variety of biological activities such as proliferation, invasion, migration, and apoptosis. It acts as an oncogene because it is abnormally expressed and promotes the progression of cancer in a variety of malignancies, including esophageal squamous cell carcinoma, non-small cell lung cancer, breast cancer, neuroblastoma, endometrial cancer, thyroid cancer, and gastric cancer. However, it was evident that NR2F1-AS1 inhibits the progression of cancer in cervical squamous cell carcinoma. CONCLUSION: NR2F1-AS1 is a potential new biomarker and therapeutic target for the treatment of different cancers."	esophagus
Preoperative hiatal hernia in esophageal adenocarcinoma; does it have an impact on patient outcomes?	BACKGROUND: The impact of hiatal hernia (HH) on oncologic outcomes of patients with esophageal adenocarcinoma (AC) remains unclear. The aim of this study was to assess the effect of pre-existing HH (≥3 cm) on histologic response after neoadjuvant treatment (NAT), overall (OS) and disease-free survival (DFS). METHODS: All consecutive patients with oncological esophagectomy for AC from 2012 to 2018 in our center were eligible for assessment. Categorical variables were compared with the X(2) or Fisher's test, continuous ones with the Mann-Whitney-U test, and survival with the Kaplan-Meier and log-rank test. RESULTS: Overall, 101 patients were included; 33 (32.7%) had a pre-existing HH. There were no baseline differences between HH and non-HH patients. NAT was used in 81.8% HH and 80.9% non-HH patients (p = 0.910), most often chemoradiation (63.6% and 57.4% respectively, p = 0.423). Good response to NAT (TRG 1-2) was observed in 36.4% of HH versus 32.4% of non-HH patients (p = 0.297), whereas R0 resection was achieved in 90.9% versus 94.1% respectively (p = 0.551). Three-year OS was comparable for the two groups (52.4% in HH, 56.5% in non-HH patients, p = 0.765), as was 3-year DFS (32.7% for HH versus 45.6% for non-HH patients, p = 0.283). CONCLUSION: HH ≥ 3 cm are common in patients with esophageal AC, concerning 32.7% of all patients in this series. However, its presence was neither associated with more advanced disease upon diagnosis, worse response to NAT, nor overall and disease-free survival. Therefore, such HH should not be considered as risk factor that negatively affects oncological outcome after multimodal treatment of esophageal AC.	esophagus
Inflammatory and Nutritional Status Influences Outcomes of Minimally Invasive Esophagectomy.	INTRODUCTION: The potential association between severe postoperative complications (SPC) and the oncological outcomes of esophageal squamous cell carcinoma (ESCC) patients according to the different Naples Prognostic Score (NPS) of the inflammatory nutritional status after minimally invasive esophagectomy (MIE) is unclear. METHODS: Kaplan-Meier survival analysis was used to evaluate overall survival (OS) and disease-free survival (DFS) between with or without SPC (Clavien-Dindo grade ≥ III) in low NPS status (NPS = 0 or 1) and high NPS status (NPS = 2 or 3 or 4) patients. Cox multivariable analysis was carried out to analyze the various independent factors of OS and DFS, and a nomogram based on SPC was established. RESULTS: A total of 20.7% (125/604) ESCC patients developed SPC after MIE. Patients with SPC exhibited poor 5-year OS and DFS compared to those without SPC (all P < 0.001). Further analysis revealed that SPC significantly reduced OS and DFS in patients with high NPS status (all P < 0.001) but had little effect on the prognosis of patients with low NPS status (all P > 0.05). Multivariable Cox analysis revealed that SPC could be an independent influence indicator for OS and DFS in patients with high NPS status. Therefore, a novel nomogram combining SPC and tumor-node-metastasis (TNM) staging has been developed, which was found to be relatively more accurate in predicting OS and DFS than TNM staging alone. CONCLUSION: Severe complications can adversely affect the long-term oncological outcome of ESCC patients with high systemic inflammatory response and malnutrition after MIE.	esophagus
M6PR- and EphB4-Rich Exosomes Secreted by Serglycin-Overexpressing Esophageal Cancer Cells Promote Cancer Progression.	Accumulating evidence shows that exosomes participate in cancer progression. However, the functions of cancer cell exosome-transmitted proteins are rarely studied. Previously, we reported that serglycin (SRGN) overexpression promotes invasion and metastasis of esophageal squamous cell carcinoma (ESCC) cells. Here, we investigated the paracrine effects of exosomes from SRGN-overexpressing ESCC cells (SRGN Exo) on ESCC cell invasion and tumor angiogenesis, and used mass spectrometry to identify exosomal proteins involved. Cation-dependent mannose-6-phosphate receptor (M6PR) and ephrin type-B receptor 4 (EphB4) were pronouncedly upregulated in SRGN Exo. Upregulated exosomal M6PR mediated the pro-angiogenic effects of SRGN Exo both in vitro and in vivo, while augmented exosomal EphB4 mediated the pro-invasive effect of SRGN Exo on ESCC cells in vitro. In addition, in vitro studies showed that manipulation of M6PR expression affected the viability and migration of ESCC cells. Both M6PR and EphB4 expression levels were positively correlated with that of SRGN in the serum of patients with ESCC. High level of serum M6PR was associated with poor overall survival rates. Taken together, this study presents the first proof that exosomal M6PR and EphB4 play essential roles in tumor angiogenesis and malignancy, and that serum M6PR is a novel prognostic marker for ESCC patients.	esophagus
The role of surveillance and salvage esophagectomy in previously treated esophageal cancer.	Esophageal cancer remains a significant cause of cancer-related mortality among men and women in the United States. The utility of surgery, as either an immediate or delayed resection in the form of esophagectomy following neoadjuvant therapy in local-regionally advanced esophageal cancer, remains controversial. While neoadjuvant therapy followed by immediate surgery is a guideline-concordant treatment, emerging data suggests that active surveillance with delayed resection at the time of local-regional recurrence may be considered.	esophagus