crossing96/oncoscreening huggingface dataset:
C5b-9 Membrane Attack Complex Formation and Extracellular Vesicle Shedding in Barrett's Esophagus and Esophageal Adenocarcinoma.	The early complement components have emerged as mediators of pro-oncogenic inflammation, classically inferred to cause terminal complement activation, but there are limited data on the activity of terminal complement in cancer. We previously reported elevated serum and tissue C9, the terminal complement component, in esophageal adenocarcinoma (EAC) compared to the precursor condition Barrett's Esophagus (BE) and healthy controls. Here, we investigate the level and cellular fates of the terminal complement complex C5b-9, also known as the membrane attack complex. Punctate C5b-9 staining and diffuse C9 staining was detected in BE and EAC by multiplex immunohistofluorescence without corresponding increase of C9 mRNA transcript. Increased C9 and C5b-9 staining were observed in the sequence normal squamous epithelium, BE, low- and high-grade dysplasia, EAC. C5b-9 positive esophageal cells were morphologically intact, indicative of sublytic or complement-evasion mechanisms. To investigate this at a cellular level, we exposed non-dysplastic BE (BAR-T and CP-A), high-grade dysplastic BE (CP-B and CP-D) and EAC (FLO-1 and OE-33) cell lines to the same sublytic dose of immunopurified human C9 (3 µg/ml) in the presence of C9-depleted human serum. Cellular C5b-9 was visualized by immunofluorescence confocal microscopy. Shed C5b-9 in the form of extracellular vesicles (EV) was measured in collected conditioned medium using recently described microfluidic immunoassay with capture by a mixture of three tetraspanin antibodies (CD9/CD63/CD81) and detection by surface-enhanced Raman scattering (SERS) after EV labelling with C5b-9 or C9 antibody conjugated SERS nanotags. Following C9 exposure, all examined cell lines formed C5b-9, internalized C5b-9, and shed C5b-9(+) and C9(+) EVs, albeit at varying levels despite receiving the same C9 dose. In conclusion, these results confirm increased esophageal C5b-9 formation during EAC development and demonstrate capability and heterogeneity in C5b-9 formation and shedding in BE and EAC cell lines following sublytic C9 exposure. Future work may explore the molecular mechanisms and pathogenic implications of the shed C5b-9(+) EV.	esophagus
Impact of frailty on the long-term outcomes of elderly patients with esophageal squamous cell carcinoma.	OBJECTIVE: We aimed to clarify the association between frailty evaluated using the clinical frailty scale (CFS) and outcomes in elderly patients with esophageal squamous cell carcinoma. METHODS: We retrospectively included 67 patients (aged ≥ 75 years) diagnosed with esophageal squamous cell carcinoma (tumor depth ≥ m3) between 2011 and 2016. The patients were retrospectively evaluated and categorized according to their CFS scores (1-7) and divided into non-frailty (scores 1-2) and frailty groups (scores 3-7). Postoperative complications, 5 year survival rate, and prognostic risk factors were analyzed. RESULTS: Significant differences in performance status, American Society of Anesthesiologists-Physical Status score, Charlson comorbidity index, and treatment type were observed between the two groups. Thirty-six patients underwent surgery, and morbidities with Clavien-Dindo grades ≥ II and ≥ IIIa were found in 72.2 and 47.2% of the patients, respectively. The remaining 31 patients underwent endoscopic resection and/or chemo (radio) therapy. The morbidity rate did not differ between the two groups. The 5 year survival rate was 75.3% overall and 92.7 and 60.8% in patients in the non-frailty and frailty groups, respectively (p = 0.007). Multivariate analysis revealed that frailty and cStage ≥ II were independent risk factors of overall survival (p = 0.005 and p = 0.013, respectively) and disease-specific survival (p = 0.048 and p = 0.027, respectively). CONCLUSIONS: Frailty greatly impacts the prognosis of elderly patients with esophageal cancer, regardless of surgical or nonsurgical treatment. The CFS score could be a useful prognostic predictor.	esophagus
Exosomal microRNAs: A Diagnostic and Therapeutic Small Bio-molecule in Esophageal Cancer.	Esophageal cancer (EC) is one of the major causes of cancer-related death worldwide. EC is usually diagnosed at a late stage, and despite aggressive therapy, the five-year survival rate of patients remains poor. Exosomes play important roles in cancer biology. Indeed, exosomes are implicated in tumor proliferation, angiogenesis, and invasion. They contain bioactive molecules such as lipids, proteins, and non-coding RNAs. Exosome research has recently concentrated on microRNAs, which are tiny noncoding endogenous RNAs that can alter gene expression and are linked to nearly all physiological and pathological processes, including cancer. It is suggested that deregulation of miRNAs results in cancer progression and directly induces tumor initiation. In esophageal cancer, miRNA dysregulation plays an important role in cancer prognosis and patients' responsiveness to therapy, indicating that miRNAs are important in tumorigenesis. In this review, we summarize the impact of exosomal miRNAs on esophageal cancer pathogenesis and their potential applications for EC diagnosis and therapy.	esophagus
MiR-106b-5p regulates esophageal squamous cell carcinoma progression by binding to HPGD.	BACKGROUND: Several studies have documented the key role of microRNAs (miRNAs) in esophageal squamous cell carcinoma (ESCC). Although the expression of the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene and miR-106b-5p are reportedly linked to cancer progression, their underlying mechanisms in ESCC remain unclear. METHODS: mRNA and miRNA expression in ESCC tissues and cells were analyzed using RT-qPCR. Luciferase and RNA pull-down assays were used to identify the interaction between miR-106b-5p and HPGD. Xenograft and pulmonary metastasis models were used to assess tumor growth and metastasis. CCK-8, BrdU, colony formation, adhesion, cell wound healing, Transwell, and caspase-3/7 activity assays, and flow cytometry and western blot analyses were used to examine the function of miR-106-5p and HPGD in ESCC cell lines. RESULTS: The findings revealed that miR-106b-5p expression was upregulated in ESCC tissues and cell lines. miR-106b-5p augmented cellular proliferation, colony formation, adhesion, migration, invasion, and proportion of cells in the S-phase, but reduced apoptosis and the proportion of cells in G1-phase. Silencing of miR-106-5p inhibited tumor growth in vivo and pulmonary metastasis. Although HPGD overexpression suppressed proliferation, colony formation, adhesion, migration, and invasion of ESCC cells, it promoted apoptosis and caused cell cycle arrest of the ESCC cells. The results also indicated a direct interaction of HPGD with miR-106b-5p in ESCC cells. Furthermore, miR-106b-5p inhibited HPGD expression, thereby suppressing ESCC tumorigenesis. CONCLUSION: Our data suggest that miR-106b-5p enhances proliferation, colony formation, adhesion, migration, and invasion, and induces the cycle progression, but represses apoptosis of ESCC cells by targeting HPGD. This suggests that the miR-106b-5p/HPGD axis may serve as a promising target for the diagnosis and treatment of ESCC.	esophagus
Minimally Invasive Esophagectomy Is Associated with Superior Survival Compared to Open Surgery.	INTRODUCTION: Minimally invasive esophagectomy (MIE) has not been associated with a long-term survival advantage compared to open esophagectomy (OE). We investigated survival differences between MIE, including laparoscopic and robotic, and OE. METHODS: Patients undergoing esophagectomy from 2010 to 2014 with T(1-4)N(0-3)M(0), adenocarcinoma or squamous cell histology, in middle or lower esophagus were queried from the National Cancer Database and stratified into groups based on their surgical procedure: robotic, laparoscopic, or OE. Propensity matching (1:1) was done between robotic and laparoscopic to produce an MIE group. The MIE group was matched to OE yielding a 1:1:2 matching of robotic:laparoscopic:OE. Postoperative outcomes and survival (Kaplan-Meier) were compared between groups. RESULTS: Prior to matching, 7,163 patients met inclusion criteria and a greater portion underwent OE (67.7%) than MIE (laparoscopic 24.9% and robotic 7.4%). Matching yielded similar groups (robotic = 527, laparoscopic = 527, and OE =1054). Compared to OE, MIE patients had a significantly greater number of nodes sampled and trended toward increased R0 resections (96.1% vs 94.3%, P = .053). OE was associated with a longer median postoperative stay (10 vs 9 days, P = .001). Mortality at 30 and 90 days was similar. However, postoperative survival for MIE was significantly greater than OE (P < .001). No survival difference existed between robotic and laparoscopic (P = .723). CONCLUSIONS: MIE is associated with increased number of nodes examined and a shorter postoperative length of stay. After propensity matching, patients undergoing MIE had better long but not short-term survival than OE. This benefit seems to be independent of the use of robotic technology.	esophagus
International Tumor Budding Consensus Conference criteria determine the prognosis of oesophageal adenocarcinoma with poor response to neoadjuvant treatment.	BACKGROUND: Neoadjuvant therapy regimens followed by surgery represent the current standard treatment of locally advanced oesophageal adenocarcinomas. Tumour regression determines prognosis, but more than half of patients do have more than 10% residual tumour after neoadjuvant therapy. In these cases, classical histopathological parameters for the determination of prognosis are of limited value. Therefore, we investigated whether tumour budding could be an additional prognostic factor for tumours with poor response to neoadjuvant therapy. METHODS: Tumour budding was assessed according to a standardized consensus quantification method as proposed by the International Tumor Budding Consensus Conference (ITBCC) in H&E-stained whole tissue slides of 278 formalin-fixed paraffin-embedded (FFPE) resected oesophageal adenocarcinomas with a poor response (> 10% vital residual tumour) to neoadjuvant therapy. RESULTS: We could demonstrate a strong positive correlation (p < 0.05) between the budding group, ypN stage and UICC tumour stage. Further, high numbers of tumour buds were a significant and independent negative prognostic marker for OS in all studied patients (HR = 1.039 (95% CI 1.012-1.066), p = 0.004). ITBCC budding groups were an independent prognostic parameter. CONCLUSIONS: Tumour budding assessed in accordance with the ITBCC criteria may aid in the prognostic stratification of locally advanced oesophageal adenocarcinoma with poor response to neoadjuvant treatment.	esophagus
Apatinib inhibits tumour progression and promotes antitumour efficacy of cytotoxic drugs in oesophageal squamous cell carcinoma.	Apatinib, a highly selective inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), inhibits the angiogenesis of tumours. The function and mechanism of apatinib in oesophageal squamous cell carcinoma (ESCC) remain unknown. In present study, we found that the development of ESCC in patients was controlled by treatment of combination of apatinib and a chemotherapeutic drug. Moreover, apatinib efficiently promotes cell apoptosis, inhibits cell proliferation, invasion, epithelial-mesenchymal transition (EMT) and activity of the Akt/mTOR pathway in ESCC cells. Western blot analysis showed that apatinib significantly increased vimentin protein levels, decreased Bcl2, matrix metalloproteinase 9 (MMP9), E-cadherin, p-Akt and p-mTOR protein levels in ESCC cells. Furthermore, apatinib enhanced chemosensitivity of cytotoxic drugs paclitaxel (TAX), 5-fluorouracil (5-FU) and cisplatin (DDP) by upregulating expression of vimentin protein, and downregulating expression of Bcl2, MMP9 and E-cadherin protein in vitro. Compared with single-agent groups, the combination of apatinib with each chemotherapeutic drug significantly repressed tumour growth and angiogenesis through blocking the expression of Ki67 and VEGFR-2 in vivo. Taken together, apatinib efficiently inhibits cell growth through blocking Bcl2 and Akt/mTOR pathway, and suppresses metastasis via inhibiting MMP9 and EMT in ESCC cells. Apatinib promoted antitumour effect of chemotherapeutic agents through promoting cell apoptosis and inhibiting EMT and angiogenesis in ESCC.	esophagus
Introduction of laparoscopic Ivor Lewis esophagectomy as hybrid procedure and comparison with open esophagectomy. A propensity-matched retrospective study.	BACKGROUND: Esophagectomy is associated with increased rate of postoperative complications, making it one of the procedures with the highest impact on patients' quality of life. Hybrid Ivor Lewis esophagectomy (HMIE) has been introduced in our clinic with the aim to reduce postoperative morbidity, without compromising on oncological outcomes. We conducted this survey to evaluate the perioperative morbidity of the new method during the introduction phase compared to open esophagectomy in two similarly matched groups of patients. METHODS: This study included the first 17 patients who underwent HMIE for esophageal cancer at a high-volume tertiary center. After generating propensity scores using the variables age, body mass index, pulmonary comorbidities, cardiac comorbidities, histologic type, and neoadjuvant treatment, 17 patients in the hybrid group were matched with 17 patients in the open group. Surgical outcomes, oncological outcomes, and postoperative complications according to the guidelines of the Esophageal Complications Consensus Group were compared between the two groups. RESULTS: Surgical and oncological outcomes were comparable between the two approaches. The rate of postoperative complications, including surgical, gastrointestinal, and pulmonary complications, were similar in the two groups. CONCLUSIONS: Our hypothesis that laparoscopy could reduce postoperative complications was not confirmed. HMIE is a safe procedure, resulting in radical oncological resection and similar morbidity with open esophagectomy. Surgeons, who are proficient in open approach and laparoscopic anti-reflux and gastric surgery, can safely adopt the hybrid approach without significant learning curve associated morbidity.	esophagus
Pepsinogen/Proton Pump Co-Expression in Barrett's Esophageal Cells Induces Cancer-Associated Changes.	EDUCATIONAL OBJECTIVE: At the conclusion of this presentation, participants should better understand the carcinogenic potential of pepsin and proton pump expression in Barrett's esophagus. OBJECTIVE: Barrett's esophagus (BE) is a well-known risk factor for esophageal adenocarcinoma (EAC). Gastric H(+) /K(+) ATPase proton pump and pepsin expression has been demonstrated in some cases of BE; however, the contribution of local pepsin and proton pump expression to carcinogenesis is unknown. In this study, RNA sequencing was used to examine global transcriptomic changes in a BE cell line ectopically expressing pepsinogen and/or gastric H(+) /K(+) ATPase proton pumps. STUDY DESIGN: In vitro translational. METHODS: BAR-T, a human BE cell line devoid of expression of pepsinogen or proton pumps, was transduced by lentivirus-encoding pepsinogen (PGA5) and/or gastric proton pump subunits (ATP4A, ATP4B). Changes relative to the parental line were assessed by RNA sequencing. RESULTS: Top canonical pathways associated with protein-coding genes differentially expressed in pepsinogen and/or proton pump expressing BAR-T cells included those involved in the tumor microenvironment and epithelial-mesenchymal transition. Top upstream regulators of coding transcripts included TGFB1 and ERBB2, which are associated with the pathogenesis and prognosis of BE and EAC. Top upstream regulators of noncoding transcripts included p300-CBP, I-BET-151, and CD93, which have previously described associations with EAC or carcinogenesis. The top associated disease of both coding and noncoding transcripts was cancer. CONCLUSIONS: These data support the carcinogenic potential of pepsin and proton pump expression in BE and reveal molecular pathways affected by their expression. Further study is warranted to investigate the role of these pathways in carcinogenesis associated with BE. LEVEL OF EVIDENCE: NA Laryngoscope, 133:59-69, 2023.	esophagus
Hsa_circ_0007142 contributes to cisplatin resistance in esophageal squamous cell carcinoma via miR-494-3p/LASP1 axis.	BACKGROUND: Chemoresistance is one of the major obstacles for tumor treatment. Circular RNAs (circRNAs) have been confirmed to play vital roles in chemoresistance of cancer, including esophageal squamous cell carcinoma (ESCC). We investigated the roles and mechanisms of circ_0007142 in cisplatin (DDP) resistance of ESCC. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine the levels of circ_0007142, DOCK1 mRNA, microRNA-494-3p (miR-494-3p) and LIM And SH3 Protein 1 (LASP1) mRNA. RNase R assay was conducted to analyze the characteristic of circ_0007142. Cell Counting Kit-8 (CCK-8) assay was performed to evaluate IC50 of DDP. Flow cytometry analysis, 5-ethynyl-2'-deoxyuridine (EdU) assay and transwell assay were carried out to examine cell apoptosis, proliferation and invasion, respectively. Dual-luciferase reporter assay was employed to verify the association between miR-494-3p and circ_0007142 or LASP1. Murine xenograft assay was conducted to investigate the role of circ_0007142 in DDP resistant in vivo. The protein level of LASP1 in tumors was measured by Immunohistochemistry (IHC) analysis. RESULTS: Circ_0007142 was upregulated in DDP-resistant ESCC tissues and cells. Circ_0007142 knockdown improved DDP sensitivity, induced cell apoptosis and hampered cell proliferation and invasion in DDP-resistant ESCC cells. Circ_0007142 functioned as the sponge for miR-494-3p and miR-494-3p inhibition reversed the impacts of circ_0007142 knockdown on DDP resistance, cell apoptosis, proliferation, and invasion. LASP1 was a target of miR-494-3p, and the effects on DDP resistance, cell apoptosis, growth, and invasion mediated by LASP1 downregulation were rescued by miR-494-3p inhibition. Moreover, circ_0007142 knockdown enhanced DDP sensitivity in vivo. CONCLUSION: Circ_0007142 improved DDP resistance of ESCC by upregulating LASP1 via sponging miR-494-3p.	esophagus
Roles of PTEN inactivation and PD-1/PD-L1 activation in esophageal squamous cell carcinoma.	Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer in China and developing countries. The purpose of this review is to summarize the roles of inactivation of the tumor suppressor gene, phosphatase and tensin homolog (PTEN), and activation of the programmed cell death protein 1 (PD-1) upon binding to its ligand (PD-L1) in the promotion of ESCC. Studies of ESCC performed in vitro and in vivo indicated that PTEN and PD-L1 function in the regulation of cell proliferation, invasion, and migration; the epithelial-mesenchymal transition; resistance to chemotherapy and radiotherapy; and the PI3K/AKT signaling pathway. Certain genetic variants of PTEN are related to susceptibility to ESCC, and PTEN and PD-L1 also function in ESCC progression and affect the prognosis of patients with ESCC. There is also evidence that the expression of PD-L1 and PTEN are associated with the progression of certain other cancers. Future studies should further examine the relationship of PD-L1 and PTEN and their possible interactions in ESCC.	esophagus
Randomized study of two endo-knives for the traction-assisted endoscopic submucosal dissection of early esophageal squamous cell carcinoma.	Needle-type devices, such as the DualKnife (Olympus, Tokyo, Japan), are widely used for traction-assisted esophageal endoscopic submucosal dissection (ESD) but require a prolonged operation time. An improved model of the ITknife (Olympus), the ITknife nano, may allow faster and easier ESD than the DualKnife. We conducted a randomized study to compare the performances of the DualKnife and the ITknife nano for traction-assisted esophageal ESD. Patients with early esophageal squamous cell carcinoma were eligible for this study. The primary outcome was the total procedure time. The secondary outcomes were submucosal dissection time, en bloc, and complete resection rates, perforation rate, and adverse events. Results Fifty patients were equally divided into two groups: the DualKnife group (D-group) and the ITknife nano group (I-group), and all underwent the assigned treatment. The I-group had significantly shorter total procedure time (36.8 vs. 60.7 min; P < 0.01) and submucosal dissection time (17.2 vs. 35.8 min; P < 0.01) than the D-group. The en bloc and complete resection rates were sufficiently high in both groups (100% and 100% in the D-group and 100% and 96% in the I-group, respectively). Significantly fewer hemostatic procedures due to intraoperative bleeding were performed in the I-group than in the D-group (0.2 vs. 1.4; P < 0.01). Delayed bleeding, perforation, or esophageal stricture did not occur in either group. The ITknife nano exhibited lower procedure time for traction-assisted esophageal ESD than the DualKnife, without increasing adverse events.	esophagus
Multi-omic cross-sectional cohort study of pre-malignant Barrett's esophagus reveals early structural variation and retrotransposon activity.	Barrett's esophagus is a pre-malignant lesion that can progress to esophageal adenocarcinoma. We perform a multi-omic analysis of pre-cancer samples from 146 patients with a range of outcomes, comprising 642 person years of follow-up. Whole genome sequencing reveals complex structural variants and LINE-1 retrotransposons, as well as known copy number changes, occurring even prior to dysplasia. The structural variant burden captures the most variance across the cohort and genomic profiles do not always match consensus clinical pathology dysplasia grades. Increasing structural variant burden is associated with: high levels of chromothripsis and breakage-fusion-bridge events; increased expression of genes related to cell cycle checkpoint, DNA repair and chromosomal instability; and epigenetic silencing of Wnt signalling and cell cycle genes. Timing analysis reveals molecular events triggering genomic instability with more clonal expansion in dysplastic samples. Overall genomic complexity occurs early in the Barrett's natural history and may inform the potential for cancer beyond the clinically discernible phenotype.	esophagus
Computed Tomography-Based Radiomics Nomogram for Predicting the Postoperative Prognosis of Esophageal Squamous Cell Carcinoma: A Multicenter Study.	OBJECTIVES: The aim of this study was to evaluate and identify the predictive value of combining CT radiomics features and clinical features to determine recurrence-free survival (RFS) and overall survival (OS) after surgery in patients with esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: A total of 372 patients with surgically and pathologically confirmed ESCC from 2 institutions were retrospectively included. All patients from institution 1 were randomized at a 7:3 ratio into a training cohort (n=206) and an internal validation cohort (n=88), and patients from institution 2 were used as an external validation cohort (n=78). The association between the radiomics features and RFS and OS was assessed in the training cohort and verified in the validation cohort. Furthermore, the performance of the radiomics nomogram was evaluated by combining the radiomics score (rad-score) and clinical risk factors. RESULTS: The radiomics nomogram that combined radiomics features and clinical risk factors was better than the clinical nomogram and radiomics model alone at predicting RFS and OS in ESCC patients. All calibration curves showed significant consistency between predicted survival and actual survival. CONCLUSION: Radiomics features could be used to stratify patients with ESCC following radical resection into high- and low-risk groups. Furthermore, the radiomics nomograms provided better predictive accuracy than other predictive models and might serve as a therapeutic decision-making reference for clinicians and be used to monitor the risks of recurrence and death.	esophagus