crossing96/oncoscreening huggingface dataset:
IGF2BP2-induced circRUNX1 facilitates the growth and metastasis of esophageal squamous cell carcinoma through miR-449b-5p/FOXP3 axis.	BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common digestive malignancies with relatively high morbidity and mortality. Emerging evidence suggests circular RNAs (circRNAs) play critical roles in tumor cell malignancy. However, the biological function and clinical significance of many circRNAs in ESCC remain elusive. METHODS: The expression level and clinical implication of circRUNX1 in ESCC tissues were evaluated using qRT-PCR. In vitro and in vivo functional studies were conducted to investigate the underlying biological effects of circRUNX1 on ESCC cell growth and metastasis. Moreover, bioinformatics analysis, RNA sequencing (RNA-seq), RNA immunoprecipitation (RIP) assays, dual-luciferase reporter assays, and rescue experiments were performed to explore the relationships between circRUNX1, miR-449b-5p, Forkhead box protein P3 (FOXP3), and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). RESULTS: CircRUNX1 was found to be significantly up-regulated in ESCC tissues and associated with TNM stage and differentiation grade. Functionally, circRUNX1 promoted ESCC cell proliferation and metastasis in vitro and in vivo. CircRUNX1 enhanced FOXP3 expression by competitively sponging miR-449b-5p. Notably, both miR-449b-5p mimics and FOXP3 knockdown restored the effects of circRUNX1 overexpression on cell proliferation and metastasis. Furthermore, IGF2BP2 binding to circRUNX1 prevented its degradation. CONCLUSIONS: IGF2BP2 mediated circRUNX1 functions as an oncogenic factor to facilitate ESCC progression through the miR-449b-5p/FOXP3 axis, implying that circRUNX1 has the potential to be a promising diagnostic marker and therapeutic target for ESCC patients.	esophagus
circCYP24A1 facilitates esophageal squamous cell carcinoma progression through binding PKM2 to regulate NF-κB-induced CCL5 secretion.	BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common gastrointestinal malignant tumor, while the molecular mechanisms have not been fully elucidated. Multiple circular RNAs have been reported to involve in the onset and progression of malignant tumors through various molecular mechanisms. However, the clinical significance and functional mechanism of most circRNAs involved in the progression of ESCC remains obscure. METHODS: RNA-Seq was used to explore potential circRNAs in participated in 5 pairs of ESCC and their corresponding normal esophageal tissues. The up-regulated circCYP24A1 was selected. Fluorescence in situ hybridization was cunducted to verificated the expression and intracellular localization of circCYP24A1 by using the tissue microarray. The Kaplan-Meier method and Cox proportional hazards model was used to examine the potential prognostic value of circCYP24A1 on overall survival of ESCC patients. The biological function were confirmed by gain- and loss-of-function approaches in vivo. mRNA expression profile microarray was proformed to investigate the downstream signaling pathways involved in circCYP24A1. RNA pull-down assay and mass spectrometry were performed to identify the proteins associated with circCYP24A1. Rescue experiments were carried out to identified hypothetical regulatory role of circCYP24A1 on ESCC progression in vivo and in virto. RESULTS: In this study, we identified circCYP24A1 in ESCC tissues by RNA sequencing, which is up-regulated in 114 cases of ESCC tissues and acts as a novel prognosis-related factor. Moreover, circCYP24A1 promoted the ability of proliferation, migration, invasion and clone formation in vitro, as well as tumor growth in vivo. Mechanistically, chemokine (C-Cmotif) ligand 5 (CCL5) is functional downstream mediator for circCYP24A1, which is screened by mRNA microarray. Moreover, circCYP24A1 physically interacts with M2 isoform of pyruvate kinase (PKM2). Rescue experiments showed that PKM2 knockdown partly reverses the promotional effects of circCYP24A1. It was revealed that circCYP24A1 increases secretion of CCL5 through the mechanism mainly by interacting with PKM2, an activator of NF-κB pathway, and thereby accelerate malignant progression of ESCC. CONCLUSIONS: Up-regulated circCYP24A1 could activate NF-κB pathway by binding PKM2, which promotes the secretion of CCL5 and accelerate malignant progression of ESCC. Our fndings recommended a novel function for circCYP24A1 as a potential effective biomarker for judging prognosis and a therapeutic target in ESCC.	esophagus
Definitive radiation therapy with dose escalation is beneficial for patients with squamous cell cancer of the esophagus.	OBJECTIVE: We report the long term follow-up, toxicity, and outcomes of patients with localized squamous cell carcinoma of the esophagus(ESCC) who underwent definitive chemo-radiotherapy(dCRT) at our institute. MATERIALS AND METHODS: Patients diagnosed with carcinoma post cricoid, upper cervical and thoracic oesophagus and treated with dCRT between January 2000 and March 2012 were retrospectively analyzed. Radiotherapy was delivered in two phases to a maximum dose of 63Gy in daily fractions of 1.8Gy using conventional or conformal techniques. OS and PFS were defined from date of registration and were calculated by Kaplan-Meier method with comparisons between different subgroups performed using log-rank test. All data were analysed using SPSS Version 22. RESULTS: Three hundred and fourteen patients with ESCC treated with dCRT were included in this analysis. Median age at presentation was 56 years and median KPS at presentation was 70. Two-third of patients were treated with conformal technique. Median dose of radiation delivered was 60Gy(range 30.6Gy-70Gy). Neoadjuvant chemotherapy was administered in about 35% patients and 57% patients received concurrent chemotherapy. About 10% patients required hospitalization during treatment due to complications and 7 patients did not complete treatment. Grade 1/2 dermatitis and mucositis was seen in 77% and 71% patients respectively. Complete response at first follow up was observed in 56% of patients. At a median follow up of 56 months, 77 patients were alive with controlled disease. The 1- and 3-yr OS were 80% and 62% respectively. Median PFS was 28 months; 1- and 3-yr PFS were 66% and 46% respectively. A higher RT dose was found to be a significant predictor for OS and PFS on both uni- and multivariate analysis. CONCLUSION: Our study highlights that the delivery of higher RT doses (≥63Gy) is feasible in this patient group and that a higher RT dose was associated with significantly better PFS and OS.	esophagus
Impact of radical dose escalation by endoluminal brachytherapy and induction chemotherapy in the definitive treatment of locally advanced esophageal cancer - A retrospective study.	BACKGROUND: The loco-regional recurrence rate remains the main concern in the treatment of esophageal cancer. However, there are controversial data regarding the benefit of dose escalation in the treatment of esophageal cancer. The study examines the implications of dose escalation with endoluminal brachytherapy after induction chemotherapy and definitive chemoradiation in cases of carcinoma esophagus. MATERIAL AND METHODS: Total 31 biopsy-proven patients with inoperable, locally advanced esophageal cancer of stage IIA-IIIB were enrolled from January 2006 till December 2018. All patients underwent two cycles of three weekly induction chemotherapy followed by definitive external beam radiotherapy of 45-50.4 Gray (Gy) at 1.8 Gy per fraction along with chemotherapy, followed by intraluminal brachytherapy boost of two fractions with 5 Gy each. Overall survival (OS) was censored at death or the last follow-up. RESULTS: Of 31 patients, 26 (83.97%) received concurrent chemotherapy and 30 (96.77%) completed radiation therapy. At the end of 3 months, 10 (32.2%), 13 (41.9%), 5 (16.1%), and 3 (9.6%) had complete response, partial response, stable disease, and progression of the disease, respectively. Distal failure was seen in five (16.1%) cases. The median OS was 28 months. OS at 2 years and 5 years was 20 (64.5%) and 9 (28.3%), respectively. At the end of 3 months, 17 (54.8%) of patients had no dysphagia, four (12.9%) of patients had improvement of more than 2 points in dysphagia score, five (16.1%) of patients had no change in the score and five (16.1%) of the patients had worsening of the dysphagia score by 1 point. Median dysphagia-free survival was 10.7 months, eight (25.8%) developed dysphagia after the dysphagia-free interval and two (6.4%) had worsening of dysphagia after treatment. There were no reported grade III or grade IV acute toxicities. CONCLUSION: The protocol has shown an acceptable survival and dysphagia-free interval. The study suggests intraluminal brachytherapy with induction chemotherapy and definitive chemoradiation is a feasible option in locally advanced esophageal cancer.	esophagus
RAD51 135G>C polymorphism in esophageal cancer and meta-analysis in gastrointestinal tract cancers.	BACKGROUND: A functional single-nucleotide polymorphism (SNP), 135G>C in the 5'UTR of the RAD51 gene, affects gene transcription activity with implications for the repair of damaged DNA related to tumorigenesis. Previous limited reported genetic studies to link the 135G>C polymorphism of RAD51 gene to the risk of gastrointestinal tract (GIT) cancers, especially esophageal cancer (EC), have been inconclusive. MATERIALS AND METHODS: The polymorphism was evaluated by RFLP-PCR in 252 EC patients and 252 healthy controls from Amritsar, Punjab, India, for case-control study. For a meta-analysis, a total of 78 studies on GIT cancers were assessed, out of which 14 eligible studies (including the present study) comprising 2842 cases and 3224 controls were included. Odds ratios (ORs) with 95% confidence intervals (CIs) and Chi-square test were used to assess the association in different inheritance models. RESULTS: The GC genotype (OR: 0.45, 95% CI: 0.29-0.68) and C allele (OR: 0.52, 95% CI: 0.36-0.75) were significantly lower (P = 0.0005) in cases as compared to controls. There was no significant association with any genetic model in the meta-analysis. CONCLUSION: C allele provides protection for EC in the studied population contrary to previous reports in Polish, Chinese population probably due to ethic differences. Compared with previous meta-analysis on individual GIT cancers, present meta-analysis included all GIT cancers but found no association.	esophagus
Alantolactone inhibits oesophageal adenocarcinoma cells through nuclear factor erythroid 2-related factor 2-mediated reactive oxygen species increment.	BACKGROUND: Oesophageal adenocarcinoma (EAC) is a highly lethal cancer associated with a rapidly rising incidence and a poor prognosis. Alantolactone, a sesquiterpene lactone isolated from inula helenium, has anti-inflammatory, antimicrobial, neuroprotective activities, and anticancer properties. OBJECTIVE: In the present study, the anticancer effects of alantolactone on the human EAC cells were investigated in vitro and in vivo. METHODS AND FINDINGS: After treated with alantolactone, the cell viability of KYAE-1, KYAE-2, OE19, and OE33 cells reduced significantly compared with that of the control cells. Alantolactone induced apoptosis of the EAC cell lines by inhibiting the protein expression levels of nuclear factor erythroid2-related factor 2 (Nrf2). Furthermore, the apoptosis-inducing effect of alantolactone was enhanced by Nrf2 knockdown while reduced by overexpression of Nrf2. Antioxidant α-tocopherol and glutathione can protect EAC cell lines against alantolactone. A xenograft nude mice model showed that alantolactone can inhibit EAC growth in vivo. CONCLUSIONS: Alantolactone inhibits oesophageal adenocarcinoma cells through Nrf2-mediated reactive oxygen species (ROS) increment. Alantolactone maybe a potential therapeutical candidate for treating EAC.	esophagus
LINC00324 promotes cell proliferation and metastasis of esophageal squamous cell carcinoma through sponging miR-493-5p via MAPK signaling pathway.	Long non-coding RNAs have been demonstrated to promote proliferation and metastasis via regulating the miRNA/mRNA regulatory axis in various malignancies. Based on our preliminary study, we investigated the mechanism of LINC00324 through miR-493-5p/MAPK1 in esophageal squamous cell carcinoma (ESCC) pathogenesis. Herein, we confirmed that LINC00324 is significantly upregulated in ESCC primary cells and esophageal squamous cell carcinoma cell line KYSE-70. Silencing of LINC00324 modulates cell proliferation markers, p21, p27, c-Myc, and Cyclin D1 and epithelial-to-mesenchymal transition markers, slug, snail, ZEB1, vimentin, ZO-1, and E-cadherin protein expression in ESCC. Through bioinformatics and dual luciferase reporter assays, we identified miR-493-5p as the direct target molecule of LINC00324. We further revealed that LINC00324 negatively regulates miR-493-5p expression in ESCC. Moreover, our multiple gain-and loss-of-functional experiments proved that a combination of miR-493-5p and LINC00324 significantly rescued ESCC cell proliferation and metastatic phenotypes. Mechanistically, LINC00324 promotes ESCC pathogenesis by acting as a competing endogenous RNA and sponges miR-493-5p activity thereby activating MAPK1 during ESCC progression. We believe that targeting LINC00324 /miR-493-5p/MAPK1 axis may provide new therapeutic avenues for ESCC.	esophagus
Effectiveness of Immune Checkpoint Inhibitors in Patients With Advanced Esophageal Squamous Cell Carcinoma: A Meta-analysis Including Low PD-L1 Subgroups.	IMPORTANCE: Immune checkpoint inhibitors (ICIs) have improved survival outcomes of patients with advanced esophageal squamous cell carcinoma in both first- and second-line settings. However, the benefit of ICIs in patients with low programmed death ligand 1 (PD-L1) expression remains unclear. OBJECTIVE: To derive survival data for patient subgroups with low PD-L1 expression from clinical trials comparing ICIs with chemotherapy in esophageal squamous cell carcinoma and to perform a pooled analysis. DATA SOURCES: Kaplan-Meier curves from the randomized clinical trials were extracted after a systematic search of Scopus, Embase, PubMed, and Web of Science from inception until October 1, 2021. STUDY SELECTION: Randomized clinical trials that investigated the effectiveness of anti-PD-1-based regimens for advanced esophageal squamous cell carcinoma and that reported overall survival (OS), progression-free survival, or duration of response were included in this meta-analysis. DATA EXTRACTION AND SYNTHESIS: Kaplan-Meier curves of all-comer populations, subgroups with high PD-L1, and those with low PD-L1 (when available) were extracted from published articles. A graphic reconstructive algorithm was used to calculate time-to-event outcomes from these curves. In studies with unreported curves for subgroups with low PD-L1 expression, KMSubtraction was used to impute survival data. KMSubtraction is a workflow to derive unreported subgroup survival data with from subgroups. An individual patient data pooled analysis including previously reported and newly imputed subgroups was conducted for trials with the same treatment line and PD-L1 scoring system. Data analysis was conducted from January 1, 2022, to June 30, 2022. MAIN OUTCOMES AND MEASURES: Primary outcomes included Kaplan-Meier curves and hazard ratios (HRs) for OS for subgroups with low PD-L1 expression. Secondary outcomes included progression-free survival and duration of response. RESULTS: The randomized clinical trials CheckMate-648, ESCORT-1st, KEYNOTE-590, ORIENT-15, KEYNOTE-181, ESCORT, RATIONALE-302, ATTRACTION-3, and ORIENT-2 were included, totaling 4752 patients. In the pooled analysis of first-line trials that evaluated a tumor proportion score (CheckMate-648 and ESCORT-1st), no significant benefit in OS was observed with immunochemotherapy compared with chemotherapy in the subgroup of patients who had a tumor proportion score lower than 1% (HR, 0.91; 95% CI, 0.74-1.12; P = .38) compared with chemotherapy. In the pooled analysis of first-line trials that evaluated combined positive score (KEYNOTE-590 and ORIENT-15), there was a significant but modest OS benefit for immunochemotherapy compared with chemotherapy in the subgroup with a combined positive score lower than 10 (HR, 0.77; 95% CI, 0.62-0.94; P = .01). CONCLUSIONS AND RELEVANCE: Findings suggest a lack of survival benefit of ICI-based regimens in the first-line setting compared with chemotherapy alone in the subgroup with a tumor proportion score lower than 1%.	esophagus
Comparison of dynamic changes in the peripheral CD8(+) T cells function and differentiation in ESCC patients treated with radiotherapy combined with anti-PD-1 antibody or concurrent chemoradiotherapy.	OBJECTIVE: The systematic immune status of cancer patients undergoing immunotherapy is little known. We prospectively identified the function and differentiation traits of peripheral CD8(+) T cells based on our phase 1b clinical trial (NCT03222440) of radiotherapy combined with camrelizumab in patients with locally advanced esophageal squamous cell carcinoma (ESCC) and compared it with concurrent chemoradiotherapy (CCRT). METHODS: 19 and 18 patients were included in the cohort of radiotherapy plus camrelizumab and cohort of CCRT treatment. By using flow cytometry, we evaluated the expression levels of PD-1, Eomes, T-bet and IFN-γ (function), CD38 and HLA-DR (activation), and differentiation subsets classified according to the expression levels of CD45RA and CD62L in peripheral CD8(+) T cells before and during treatment. RESULTS: Effective binding of anti-PD-1 antibody camrelizumab with PD-1 on CD8(+) T cells was detected during treatment. Both two treatments elevated the expression levels of activation molecules CD38 and HLA-DR on CD8(+) T cells. PD-1(+)CD8(+) T cells had more activation features than PD-1(-)CD8(+) T cells in two groups and the treatments did not alter these differences. The two treatments activated both PD-1(+) and PD-1(-) CD8(+) T cells. PD-1(+)CD8(+) T cells had less Naïve and TEMRA but more Tcm and Tem than PD-1(-)CD8(+) T cells in two groups and both two treatments changed the ratio of memory T cells in PD-1(+) and PD-1(-) cells. RT plus camrelizumab treatment reduced Naïve T cells and TEMRA subsets both in PD-1(+) and PD-1(-) CD8(+) T cells while elevated Tcm subset in PD-1(+)CD8(+) T cells and Tem subset in PD-1(-)CD8(+) T cells. CCRT elevated Tcm subset and reduced TEMRA subset in PD-1(-)CD8(+) T cells while did not change any subset in PD-1(+)CD8(+) T cells. Furthermore, patients undergoing radiotherapy plus immunotherapy were found to obtain better prognosis than those receiving CCRT. CONCLUSIONS: This study identified the dynamic changes of systematic immune status of patients undergoing treatment. The two treatments had similar activation effects on peripheral CD8(+) T cells with different PD-1 properties but had different effects on their differentiation status. These results provided potential clues to the reasons underlying the difference in prognosis of the two treatments.	esophagus
A matched cohort comparison of endoscopic resection, chemoradiation and esophagectomy in the treatment of early-stage esophageal squamous cell carcinoma.	BACKGROUND: The efficacy of endoscopic resection in early-stage esophageal squamous cell carcinoma has not been defined. METHODS: We queried the National Cancer Database to identify patients presenting with cT1N0M0 esophageal squamous cell cancer between 2004 and 2017. Transitive match methods were used to 1:1:1 propensity match patients undergoing endoscopic resection to patients undergoing esophagectomy and those undergoing definitive chemoradiotherapy. Kaplan Meier method was used to compare 5-year overall survival profiles for matched cohorts. RESULTS: 301 patients (19%) underwent endoscopic resection; 497 (32%) esophagectomy; 767 (49%) chemoradiation. On comparison of matched cohorts, patients undergoing chemoradiation demonstrated lower rates of survival than those undergoing esophagectomy (32% vs. 59%, p < 0.0001) while those undergoing endoscopic resection demonstrated rates comparable to patients undergoing esophagectomy (53% vs. 59%, p = 0.77). CONCLUSIONS: For cT1N0M0 esophageal squamous cell cancer, endoscopic resection is associated with rates of survival similar to those following esophagectomy and better than those following definitive chemoradiation.	esophagus
Robotic Esophagectomy Trends and Early Surgical Outcomes: The US Experience.	BACKGROUND: Recent esophagectomy trends were evaluated to describe the shift in surgical approach and outcomes using The Society of Thoracic Surgeons General Thoracic Surgery Database. METHODS: All patients who underwent an esophagectomy with gastric conduit from 2015 to 2019 were identified and analyzed according to original intended approach. After performing volume trend analysis of patients, operative outcomes were evaluated. RESULTS: Among 10,607 patients, esophagectomy was open in 5763 (54.3%), minimally invasive (MIE) in 3524 (33.2%), and robotic (RAMIE) in 1320 (12.4%). Within 5 years, MIE and RAMIE combined rose to majority approach (open from 58% to 42% of annual volume). While MIE and RAMIE were associated with higher rates of anastomotic leak, loss of conduit, pulmonary embolus, and reoperation, R0 resection and harvested number of lymph nodes exceeded those in open approaches. Operative mortality did not differ by approach (3.21% open vs 2.72% MIE vs 2.50% RAMIE; P = .2329). On multivariable analysis, RAMIE was independently associated with higher rate of anastomotic leak compared to open (adjusted odds ratio 1.53, 95% CI 1.14-2.04), while both MIE and RAMIE had lower mean length of stay. Propensity matching of 1320 pairs found a higher risk of anastomotic leak requiring surgery for RAMIE compared with MIE (adjusted odds ratio 1.39, 95% CI 1.01-1.92). CONCLUSIONS: In less than a decade, the dominant surgical approach in The Society of Thoracic Surgeons General Thoracic Surgery Database has become minimally invasive (RAMIE and MIE). While anastomotic leak and reoperation, more common in RAMIE, require a technical solution, these complications have not raised operative mortality. Further studies are needed to address long-term results and oncologic outcome.	esophagus
Single cell sequencing revealed the mechanism of PD-1 resistance affected by the expression profile of peripheral blood immune cells in ESCC.	BACKGROUND: Esophageal squamous carcinoma (ESCC) is a highly lethal malignancy with poor prognosis. The effect of transcriptome characteristics of patient immune microenvironment (TME) on the efficacy of immunosuppressive agents is still poorly understood. METHODS: Here we extracted and isolated immune cells from peripheral blood of patients with PD-1 monoclonal antibody sensitivity and resistance, and conducted deep single-cell RNA sequencing to describe the baseline landscape of the composition, lineage, and functional status of infiltrating immune cells in peripheral blood of patients with esophageal cancer. RESULTS: The transcriptome characteristics of immune cells were comprehensively analyzed, and the dynamic changes of cell percentage, heterogeneity of cell subtypes and interactions between cells were explained. Co-expression and pedigree tracking based on T-cell antigen receptors revealed a significant proportion of highly migratory intertissue-effector T cells. GO and KEGG enrichment pathway Analysis of CD8(+) effect-T cells ESCC_S group and ESCC_D1,2 group, found that in the up-regulated enrichment pathway, ESCC_S group enriched more PD-L1 and PD-1 checkpoint pathways expressed in tumors (JUN/NFKBIA/FOS/KRAS/IFNG), which also exist in T cell receptor signaling pathways. MT2A, MT1X and MT1E were differentially expressed in ESCC patients with PD-1 monoclonal antibody resistance, which may be related to the resistance of PD-1 mMAB. CONCLUSIONS: This study has an in-depth understanding of the influence of peripheral immune cell infiltration on the sensitivity of monoclonal antibody PD-1 in patients with esophageal cancer, which is helpful to promote the immunotherapy of patients with esophageal cancer.	esophagus