crossing96/oncoscreening huggingface dataset:
Role of interferon alpha-inducible protein 6 in modulating the proliferation, apoptosis and senescence of oesophageal squamous cell carcinoma cells.	Oesophageal cancer is one of the most malignant tumors worldwide. Dysfunction of interferon alpha-inducible protein 6 (IFI6) has been implicated in numerous human diseases, including cancer. We performed the study to investigate the function and potential molecular pathways of IFI6 in oesophageal squamous cell carcinoma (ESCC) cells. IFI6 expression was analysed using databases-derived data and paraffin-embedded tissue samples. CCK-8-based analyses and EdU staining, colony formation, β-galactosidase staining and Annexin V/PI double-staining assays were used to determine the influence of IFI6 on cell growth, senescence and apoptosis. Tumor growth in vivo was investigated in mouse xenograft models. RNA sequencing (RNA-seq) was performed to identify the transcripts and pathways affected by IFI6. The results showed that IFI6 expression was elevated in ESCC and correlated with poor clinical prognosis (P<0.05). IFI6 was overexpressed and silenced in TE-1 and TE-10 cells using lentiviruses. Upregulation of IFI6 promoted cell growth both in vitro and in vivo, whereas downregulation induced opposite effects. IFI6 overexpression inhibited cell senescence and apoptosis but did not influence cell cycle progression, while IFI6 downregulation increased cell senescence and apoptosis. RNA-seq revealed that 3 mRNAs (EPHA5, CLIP1 and GTF2F2) were consistently associated with both IFI6 overexpression and silencing. IFI6 appeared to modulate TE-1 cells via complex mechanisms. In conclusion, IFI6 plays a positive role in the proliferation of ESCC cells both in vitro and in vivo, which could be a novel therapeutic target for treating ESCC.	esophagus
RNF149 confers cisplatin resistance in esophageal squamous cell carcinoma via destabilization of PHLPP2 and activating PI3K/AKT signalling.	Chemo-resistance has been identified as a crucial factor contributing to tumor recurrence and a leading cause of worse prognosis in patients with ESCC. Therefore, unravel the critical regulators and effective strategies to overcome drug resistance will have a significant clinical impact on the disease. In our study we found that RNF149 was upregulated in ESCC and high RNF149 expression was associated with poor prognosis with ESCC patients. Functionally, we have demonstrated that overexpression of RNF149 confers CDDP resistance to ESCC; however, inhibition of RNF149 reversed this phenomenon both in vitro and in vivo. Mechanistically, we demonstrated that RNF149 interacts with PH domain and leucine rich repeat protein phosphatase 2 (PHLPP2) and induces E3 ligase-dependent protein degradation of PHLPP2, substantially activating the PI3K/AKT signalling pathway in ESCC. Additionally, we found that inhibition of PI3K/AKT signalling pathway by AKT siRNA or small molecule inhibitor significantly suppressed RNF149-induced CDDP resistance. Importantly, RNF149 locus was also found to be amplified not only in ESCC but also in various human cancer types. Our data suggest that RNF149 might function as an oncogenic gene. Targeting the RNF149/PHLPP2/PI3K/Akt axis may be a promising prognostic factor and valuable therapeutic target for malignant tumours.	esophagus
Artificial Intelligence-Triaged 3-Dimensional Pathology to Improve Detection of Esophageal Neoplasia While Reducing Pathologist Workloads.	Early detection of esophageal neoplasia via evaluation of endoscopic surveillance biopsies is the key to maximizing survival for patients with Barrett's esophagus, but it is hampered by the sampling limitations of conventional slide-based histopathology. Comprehensive evaluation of whole biopsies with 3-dimensional (3D) pathology may improve early detection of malignancies, but large 3D pathology data sets are tedious for pathologists to analyze. Here, we present a deep learning-based method to automatically identify the most critical 2-dimensional (2D) image sections within 3D pathology data sets for pathologists to review. Our method first generates a 3D heatmap of neoplastic risk for each biopsy, then classifies all 2D image sections within the 3D data set in order of neoplastic risk. In a clinical validation study, we diagnose esophageal biopsies with artificial intelligence-triaged 3D pathology (3 images per biopsy) vs standard slide-based histopathology (16 images per biopsy) and show that our method improves detection sensitivity while reducing pathologist workloads.	esophagus
RIG-I promotes cell proliferation in esophageal squamous cell carcinoma by facilitating p21 degradation.	Retinoic acid-inducible gene-I (RIG-I) is considered a key sensor for host recognition of RNA virus infections. Recent studies have shown that RIG-I also regulates carcinogenesis. However, the role of RIG-I in esophageal squamous cell carcinoma (ESCC) remains unclear. We investigated the RIG-I expression in ESCC cells using a public database, immunohistochemistry, and Western blotting. We evaluated the proliferative activity of ESCC cells using CCK-8, colony formation, and EdU staining assays. Further, we determined the ESCC cell-cycle changes using flow cytometry and the ubiquitination of p21 in the cells using cycloheximide chase and ubiquitination assays. Finally, we verified the in vivo effects of RIG-I on ESCC cells by constructing xenograft models. RIG-I was highly expressed in ESCC cells and significantly promoted their proliferation and cell-cycle. Moreover, RIG-I knockdown inhibited xenograft growth in nude mice. Furthermore, RIG-I accelerated the cell-cycle by promoting the ubiquitination and degradation of p21. Overall, this study revealed that the increased expression of RIG-I due to ESCC accelerated the progression of esophageal cancer by promoting the ubiquitination and degradation of p21, which is related to the prognosis of ESCC. Thus, RIG-I may be a novel therapeutic target for ESCC treatment.	esophagus
Long-term outcomes of large balloon dilatation for benign anastomotic stricture following surgical resection of esophageal cancer.	Surgical resection of esophageal cancer may result in benign anastomotic strictures, which are usually treated by balloon dilatation. Here we reported the long-term outcomes of large balloon dilatation for benign anastomotic strictures secondary to esophagectomy for esophageal cancer. From February 2011 to December 2016, 27 esophageal cancer patients underwent large balloon dilatation for benign strictures following surgical resection. Clinical success rate, number of dilatation sessions, complication rate, and mortality rate were evaluated. A total of 27 patients developed a benign stricture at the esophagectomy site. A total of 50 dilatation sessions of large balloon were performed, with a mean of 1.8 sessions per patients (range 1.0-5.0). Only 1 perforation was observed (2.0% per dilatation session), and required no surgery. No procedure-related deaths were recorded. Large balloon dilation was technically successful in the remained 26 patients (96.3%). Dysphagia score and stricture index decreased significantly (P < .0001). Proximal diameter of stricture, stricture diameter and length decreased significantly. Patients were followed up for 36.3 ± 7.1 months, and 14 patients survived without dysphagia. The survival rates were 95.0%, 69.1%, 34.5% for 1, 5, and 9 years, respectively. The median survival was 96.0 months. Large balloon dilatation can be a safe and feasible treatment for benign anastomic strictures following surgical resection of esophageal cancer, with a low perforation rate. However, further study compared with small balloon dilatation is warranted.	esophagus
Severe Lymphopenia During Chemoradiation Therapy for Esophageal Cancer: Comprehensive Analysis of Randomized Phase 2B Trial of Proton Beam Therapy Versus Intensity Modulated Radiation Therapy.	PURPOSE: Lymphocytes play an important role in antitumor immunity; however, they are also especially vulnerable to depletion during chemoradiation therapy (CRT). The purpose of this study was to compare the incidence of grade 4 lymphopenia (G4L) between proton beam therapy (PBT) and intensity modulated photon radiation therapy (IMRT) in patients with esophageal cancer treated with CRT in a completed randomized trial and to ascertain patient heterogeneity to G4L risk based on treatment and established prognostic factors. METHODS AND MATERIALS: Between April 2012 and March 2019, a single-institution, open-label, nonblinded, phase 2 randomized trial (NCT01512589) was conducted at the University of Texas MD Anderson Cancer Center. Patients were randomly assigned to IMRT or PBT, either definitively or preoperatively. This secondary analysis of the randomized trial was G4L during concurrent CRT according to Common Terminology Criteria for Adverse Events version 5.0. RESULTS: Among 105 patients evaluable for analysis, 44 patients (42%) experienced G4L at a median of 28 days after the start date of concurrent CRT. Induction chemotherapy (P = .003), baseline absolute lymphocyte count (P < .001), radiation therapy modality (P = .002), and planning treatment volume (P = .033) were found to be significantly associated with G4L. Multivariate classification analysis partitioned patients into 5 subgroups for whom the incidence of G4L was observed in 0%, 14%, 35%, 70%, and 100% of patients. The benefit of PBT over IMRT was most pronounced in patients with an intermediate baseline absolute lymphocyte count and large planning treatment volume (P = .011). CONCLUSIONS: This is the first prospective evidence that limiting dose scatter by PBT significantly reduced the incidence of G4L, especially in the intermediate-risk patients. The implication of this immune-sparing effect of PBT, especially in the context of standard adjuvant immunotherapy, needs further examination in the current phase 3 randomized trials.	esophagus
Genome-wide methylation profiling identified methylated KCNA3 and OTOP2 as promising diagnostic markers for esophageal squamous cell carcinoma.	BACKGROUND: Early detection of esophageal squamous cell carcinoma (ESCC) can considerably improve the prognosis of patients. Aberrant cell-free DNA (cfDNA) methylation signatures are a promising tool for detecting ESCC. However, available markers based on cell-free DNA methylation are still inadequate. This study aimed to identify ESCC-specific cfDNA methylation markers and evaluate the diagnostic performance in the early detection of ESCC. METHODS: We performed whole-genome bisulfite sequencing (WGBS) for 24 ESCC tissues and their normal adjacent tissues. Based on the WGBS data, we identified 21,469,837 eligible CpG sites (CpGs). By integrating several methylation datasets, we identified several promising ESCC-specific cell-free DNA methylation markers. Finally, we developed a dual-marker panel based on methylated KCNA3 and OTOP2 , and then, we evaluated its performance in our training and validation cohorts. RESULTS: The ESCC diagnostic model constructed based on KCNA3 and OTOP2 had an AUC of 0.91 [95% CI: 0.85-0.95], and an optimal sensitivity and specificity of 84.91% and 94.32%, respectively, in the training cohort. In the independent validation cohort, the AUC was 0.88 [95% CI: 0.83-0.92], along with an optimal sensitivity of 81.5% and specificity of 92.9%. The model sensitivity for stage I-II ESCC was 78.4%, which was slightly lower than the sensitivity of the model (85.7%) for stage III-IV ESCC. CONCLUSION: The dual-target panel based on cfDNA showed excellent performance for detecting ESCC and might be an alternative strategy for screening ESCC.	esophagus
Clinical Impact of Enhanced Recovery After Esophagectomy in Patients With Esophageal Cancer.	BACKGROUND/AIM: The enhanced recovery after surgery (ERAS) program is expected to improve perioperative outcomes in patients with esophageal cancer. However, how ERAS impacts the postoperative body composition and factors related to compliance rate of ERAS have not been fully investigated. PATIENTS AND METHODS: The study included 252 consecutive patients with thoracic esophageal cancer who underwent minimally invasive esophagectomy. We compared the postoperative outcomes including body composition between the old perioperative program and the new one that aimed to shorten postoperative length of stay (LOS). Compliance-related clinical factors were also examined. RESULTS: From 252 patients, 129 underwent the old program and 123 the new program. Postoperative LOS, postoperative complications, and hospital costs were reduced with the new program. Body weight loss was significantly improved with the new program at discharge and 3-months after esophagectomy (94.9% vs. 96.6%, p=0.013, 89.5% vs. 91.1%, p=0.028, respectively). Patients in the new program had better body composition at discharge than those in the old program [body fat mass (91.6% vs. 94.1%), lean body mass (95.2% vs. 97.2), and skeletal muscle mass (95.3% vs. 97.0%)]. Major reasons for incompliance were dysphagia, pneumonia, and anastomotic leakage. Multivariate analysis revealed that age ≥70 years at surgery and sex (male) were independent risk factors for incompliance with the postoperative program. CONCLUSION: The new ERAS program aimed to shorten postoperative LOS had clinical benefits in body composition early after esophagectomy. Personalized ERAS programs based on age might lead to better postoperative outcomes because of low compliance rates for older patients.	esophagus
Prognostic analysis and treatment utilization of different treatment strategies in elderly esophageal cancer patients with distant metastases: a SEER database analysis.	PURPOSE: The purpose of this study was to explore which therapeutic strategy is more beneficial for elderly esophageal cancer (EC) patients with distant metastasis, the treatment utilization status and the screening of factors related to prognosis, so as to better guide the treatment of these patients. METHODS: Patients in the Surveillance Epidemiology and End Results (SEER) database were divided into chemoradiotherapy (Group A), chemotherapy (Group B), radiotherapy (Group C), and no treatment (Group D) according to different treatment methods. Propensity score matching (PSM) was performed to adjust for baseline differences between the two groups. Overall survival (OS) and esophageal cancer-specific survival (ECSS) was calculated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: A total of 7027 patients were included in this study, 5739 males (81.7%) and 1288 females (18.3%) with the median age was 70 (60-98). In the original cohort, the number of patients in the four groups was 2260 (Group A), 2087 (Group B), 945 (Group C) and 1735 (Group D), respectively. After PSM, there was no significant difference in mean OS (A vs B, 13.5 months VS 13.4 months, P = 0.511) and mean ECSS (A vs B, 15.6 vs 15.5 months, P = 0.374), while both OS (B vs C, 7 vs 3 months, P < 0.001) and ECSS (B vs C, 8 vs 3 months, P < 0.001) of chemotherapy alone were significantly better than those of radiotherapy alone. Subgroup analysis of patients older than 80 years showed that the median OS (A vs B, 7 vs 6 months) and median ECSS (A vs B, 8 vs 7 months) of Group A were significantly better than those of Group B (P < 0.05). In addition, all patients were randomly divided into a training set and a validation set with a ratio of 7:3. Based on the independent risk factors for OS, a nomogram model was constructed and validated. CONCLUSION: For elderly EC patients with distant metastasis, aggressive treatment was still necessary after a comprehensive assessment of the patient's physical condition, especially for patients over 80 years old, and chemoradiotherapy maybe still the first choice. In addition, a nomogram model was constructed to intuitively and accurately evaluate the prognosis of this population.	esophagus
Clinical implications of dose to functional lung volumes in the trimodality treatment of esophageal cancer.	BACKGROUND: Trimodality treatment, i.e., neoadjuvant chemoradiotherapy (nCRT) followed by surgery, for locally advanced esophageal cancer (EC) improves overall survival but also increases the risk of postoperative pulmonary complications. Here, we tried to identify a relation between dose to functional lung volumes (FLV) as determined by 4D-CT scans in EC patients and treatment-related lung toxicity. MATERIALS AND METHODS: All patients with EC undergoing trimodality treatment between 2017 and 2022 in UZ Leuven and scanned with 4D-CT-simulation were selected. FLVs were determined based on Jacobian determinants of deformable image registration between maximum inspiration and expiration phases. Dose/volume parameters of the anatomical lung volume (ALV) and FLV were compared between patients with versus without postoperative pulmonary complications. Results of pre- and post-nCRT pulmonary function tests (PFTs) were collected and compared in relation to radiation dose. RESULTS: Twelve out of 51 EC patients developed postoperative pulmonary complications. ALV was smaller while FLV10Gy and FLV20Gy were larger in patients with complications (respectively 3141 ± 858mL vs 3601 ± 635mL, p = 0.025; 360 ± 216mL vs 264 ± 139mL, p = 0.038; 166 ± 106mL vs 118 ± 63mL, p = 0.030). No differences in ALV dose-volume parameters were detected. Baseline FEV1 and TLC were significantly lower in patients with complications (respectively 90 ± 17%pred vs 102 ± 20%pred, p = 0.033 and 93 ± 17%pred vs 110 ± 13%pred, p = 0.001), though no other PFTs were significantly different between both groups. DLCO was the only PFT that had a meaningful decrease after nCRT (85 ± 17%pred vs 68 ± 15%pred, p < 0.001) but was not related to dose to ALV/FLV. CONCLUSION: Small ALV and increasing FLV exposed to intermediate (10 to 20 Gy) dose are associated to postoperative pulmonary complications. Changes of DLCO occur during nCRT but do not seem to be related to radiation dose to ALV or FLV. This information could attribute towards toxicity risk prediction and reduction strategies for EC.	esophagus
Combine radiotherapy and immunotherapy in esophageal squamous cell carcinoma.	Immune checkpoint inhibitors(ICIs) have improved the survival of advanced esophageal squamous cell carcinoma (ESCC) patients. Radiotherapy is one of the common therapies to treat esophageal cancer. However, whether combination radiation therapy can increase the efficacy of immunotherapy is still up for debate. Radiotherapy combined with immunotherapy has proven to be a reliable and effective treatment for tumors, and it can work in combination with immunotherapy to achieve better anti-tumor effects. This review aims to discuss the efficacy and safety of combining radiotherapy and immunotherapy to treat ESCC by stages as well as the optimum radiotherapy dose and target volume, with a summary of clinical trials in ESCC.	esophagus
Esophageal Dysbiosis in Achalasia and Cancer Development: A Critical Review.	BACKGROUND: Microorganisms provide various benefits to their human hosts, including assisting with digestion, synthesizing certain vitamins, developing the gastrointestinal and immune systems, regulating metabolism, and protecting against some pathogens. However, microbial imbalances can cause tissue damage and contribute to inflammatory disorders and cancers. Microbial dysbiosis refers to an imbalance or disruption in the normal composition and function of the microbial communities that inhabit various body parts, including the gut, oral cavity, skin, and reproductive tract. Emerging research suggests that microbial dysbiosis plays a significant role in cancer development and progression. This issue is particularly relevant in achalasia, in which food stasis, changes in endoluminal pH, and poor esophageal clearance might contribute to esophageal microbial dysbiosis. This study aimed to evaluate the association between dysbiosis and esophageal cancer development, focused on esophageal dysmotility disorders. METHODS: This study is a critical review, gathering the current evidence for the association between dysbiosis and the development of esophageal cancer. RESULTS: Studies have shown that microbiota play a role in cancer development, although the mechanisms for how they do so are not yet fully understood. One possible explanation is that microbiota alterations can lead to chronic inflammation, promoting cancer cell growth. Additionally, some bacteria produce toxins that can damage DNA and cause genomic instability, and certain bacterial products can promote tumor growth. CONCLUSION: Despite the close relationship between dysbiosis and cancer development in esophageal dysmotility disorders, further investigations are still needed to elucidate the precise mechanisms by which dysbiosis contributes to cancer development and to identify potential therapeutic interventions targeting the microbiota to prevent or treat cancer.	esophagus
Impact of retention index on the neoadjuvant chemotherapy effect and the prognosis in oesophageal cancer.	OBJECTIVE: The relationship between retention index calculated from dual-time point 18F-fluorodeoxyglucose positron emission tomography-computed tomography and oesophageal cancer prognosis remains unknown. This study aimed to determine usefulness of retention index as a predictor of long-term prognosis of oesophageal cancer and neoadjuvant chemotherapy efficacy. METHODS: A total of 151 patients with oesophageal cancer who underwent esophagectomy were evaluated retrospectively in this study. We acquired positron emission tomography scans 60 and 120 min (SUVmax1 and SUVmax2, respectively) after the intravenous administration of 3.7 Mbq/kg 18F-fluorodeoxyglucose. The patients were divided into two groups: high-retention index (retention index ≥29%, 107 patients) and low-retention index (retention index <29%, 44 patients). Retention index was calculated as follows: retention index (%) = [(SUVmax2 - SUVmax1)/SUVmax1] × 100. RESULTS: The overall survival and relapse-free survival rates in the high-retention index group were significantly lower than those in the low-retention index group (P < 0.001). Our multivariate analysis identified that the high-retention index group contained independent risk factors for overall survival (hazard ratio: 2.44, P = 0.009) and relapse-free survival (hazard ratio: 2.61, P = 0.002). The high-retention index group exhibited a lower partial response rate to neoadjuvant chemotherapy evaluated by computed tomography (P < 0.001) and a lower pathological therapeutic effect in the resected specimen (P = 0.019) than the low-retention index group. CONCLUSIONS: The retention index was associated with neoadjuvant chemotherapy responses and long-term prognosis for oesophageal cancer.	esophagus