crossing96/oncoscreening huggingface dataset:
MicroRNA-384 inhibits the progression of esophageal squamous cell carcinoma through blockade of the LIMK1/cofilin signaling pathway by binding to LIMK1.	INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) represents an aggressive malignancy often accompanied with a poor prognosis. Owing to the poor mortality and morbidity rates associated with this malignancy, a deeper understanding of the finer molecular changes that occur in ESCC is required in order to identify novel potential targets for early detection and therapy. At present the mechanism by which ESCC functions on a molecular level is not fully understood. Hence, the aim of the present study was to ascertain as to whether microRNA-384 (miR-384) influences the progression of ESCC. MATERIAL AND METHODS: Bioinformatics analysis was initially conducted to identify ESCC-related differentially expressed genes and predict regulatory miRs. After the target relationship between miR-384 and LIMK1 had been verified, the expression of miR-384 and LIMK1 in the EC9706 cell line was altered in an attempt to investigate the regulatory roles of miR-384 in the expression of the LIMK1/cofilin signaling pathway-related genes, cell proliferation, invasion, cell cycle distribution and apoptosis, in addition to lymph node metastasis (LNM) and tumor growth in nude mice. RESULTS: Microarray-based gene expression profiling indicated that miR-384 affected the progression of ESCC through the LIMK1-mediated LIMK1/cofilin signaling pathway. Furthermore, miR-384 and Bax were observed to be poorly expressed, while LIMK1, cofilin and Bcl-2 were highly expressed in ESCC. The obtained evidences indicating that miR-384 targeted and negatively regulated LIMK1. Upregulation of miR-384 or LIMK1 inhibition was determined to block the LIMK1/cofilin signaling pathway, repress cell proliferation, invasion, cell cycle, LNM and tumor growth, while promote cell apoptosis in ESCC. CONCLUSION: Collectively, based on the key findings of the study, miR-384 could sequester LIMK1, which acts to suppress activation of the LIMK1/cofilin signaling pathway, thus ultimately inhibiting the development and progression of ESCC.	esophagus
Zerumbone inhibits migration in ESCC via promoting Rac1 ubiquitination.	Zerumbone has been reported to maintain the anti-cancer effects in many malignant cells. However, the effect and mechanism of Zerumbone on esophageal squamous cell carcinomas (ESCC) is rarely investigated. Here we report the inhibitory effect of Zerumbone (hereinafter referred to as ZER) on ESCC migration and the underlying molecular mechanism. ZER could inhibit the migration of human esophageal squamous cancer KYSE-30 cells and KYSE-150 cells. ZER induced Rac1 protein down-regulation in a dose- and time-dependent manner. The reduction of Rac1 protein was crucial for ZER-induced inhibition of cell migration, as Rac1 knockdown could enhance ZER-induced inhibition of cell migration. We further demonstrated that the decrease of Rac1 after ZER treatment is via proteasome-dependent degradation pathway, and ZER treatment drastically enhanced ubiquitination of Rac1, which finally caused Rac1 degradation. Collectively, our results indicated that ZER inhibits cell migration by suppressing Rac1 expression. This suppresion is achieved through promoting Rac1 ubiquitination and degradation. Thus, the study raises the possibility of ZER as a potential drug for ESCC due to its ability to inhibit cell migration.	esophagus
Long non-coding RNA XIST promotes the development of esophageal cancer by sponging miR-494 to regulate CDK6 expression.	OBJECTIVE: Esophageal cancer is one of the deadliest cancers worldwide occurring at upper gastrointestinal tract. This study aimed to explore the possible role of long non-coding RNA X Inactive Specific Transcript (XIST) in the development of esophageal cancer. MATERIAL AND METHODS: The lncRNA XIST expressions both in esophageal cancer tissues and in cells were investigated. The TE-1 and SKGT-4 cells were transfected with LV-sh-XIST and LV-scramble for the further detection of the effects of XIST expression on cell biological processes, including proliferation, apoptosis and the expression of apoptosis-related proteins, migration, invasion and the expression of epithelial-mesenchymal transition markers. Additionally, the regulatory relationships between lncRNA XIST and miR-494, between miR-494 and CDK6, between miR-494/CDK6 and JAK2/STAT3 pathway were investigated. RESULTS: LncRNA XIST was overespressed in esophageal cancer tissues and cells. Suppression of XIST significantly inhibited the proliferation, migration and invasion, but induced apoptosis of two kinds of cells, TE-1 and SKGT-4. Moreover, miR-494 was down-regulated in esophageal cancer tissues and cells. XIST could sponge miR-494 and inhibition of miR-494 reversed the effects of XIST suppression on the malignant behaviors of TE-1 cells. Also, CDK6 was a target of miR-494 and CDK6 knockdown reversed the effects of miR-494 inhibition on the malignant behaviors of TE-1 cells. Besides, the expression of p-JAK2 and p-STAT3 was increased after miR-494 inhibition, which was reversed after inhibition of miR-494 and CDK6 at the same time. CONCLUSIONS: The data presented in this study revealed that XIST abnormal expression may play an oncogenic role in the development of esophageal cancer via miR-494/CDK6 axis through JAK2/STAT3 signal pathway. This study may provide theoretical basis for the molecular mechanism investigation of esophageal cancer.	esophagus
Endoscopic submucosal dissection followed by chemoradiotherapy for superficial esophageal cancer: choice of new approach.	BACKGROUND: The standard treatment for superficial esophageal cancer (SEC) involving muscularis mucosal (T1a-MM) or submucosal (T1b) invasion has been the surgical resection of the esophagus. However, esophagectomy with extended lymph node dissection is highly invasive. Recent reports have shown that endoscopic submucosal dissection (ESD) followed by chemoradiotherapy (CRT) has promising results and might become a new therapeutic approach. This retrospective study aimed to elucidate the efficacy and safety of this new treatment. METHODS: Patients with clinical stage T1b tumor without apparent metastasis treated with ESD followed by CRT from 2014 to 2017 (the CRT group) were included. The outcomes on disease-free survival (DFS) of this group were compared with those of consecutive patients in a historical control group who underwent ESD followed by esophagectomy (the esophagectomy group) between 2008 and 2015. RESULTS: Of 32 patients analyzed, 16 were in the CRT group and 16 with similar stage cancer were in the esophagectomy group. Radiotherapy was completed in all patients, and the incidence of grade ≥ 3 nonhematologic adverse events was 6%. The 2-year overall survival rates were 100%, and locoregional control was achieved in all patients in the CRT group, and the 2-year DFS rates were 88 and 100% for the CRT and esophagectomy groups, respectively, without significant differences. CONCLUSIONS: Our data confirmed our new approach as being safe and effective for locoregional control and may provide a nonsurgical treatment option for patients with clinical stage T1b tumors.	esophagus
Prognostic role of neutrophil-lymphocyte ratio in esophageal cancer: A systematic review and meta-analysis.	BACKGROUND: The prognostic role of neutrophil-to-lymphocyte ratio (NLR) in esophageal cancer (EC) remains controversial. METHODS: The aim of this study was to evaluate the association between NLR and oncologic outcome of EC patients through a meta-analysis. A systematic search was performed in PubMed, Web of Science and Embase for relevant studies. Meta-analysis was performed using hazard ratio (HR) and95% confidence interval (CI) as effect measures. RESULTS: Finally, 33 articles with 11,039patients were included in our study. The synthesized results indicated that the elevated NLR was negatively related to overall survival (OS) (HR = 1.39, 95% CI: 1.23-1.54). When the patients were stratified according to country, pathological type, treatment strategies, sample size, and different HR estimate method, high NLR was also significantly correlated with poor OS. Similarly, elevated NLR was also associated with shorter disease-free survival (DFS), progress-free survival (PFS), relapse-free survival (RFS), and cancer-specific survival (CSS). CONCLUSION: The elevated pretreatment NLR is associated with poor oncological outcomes in patients with EC. NLR may be a significant predictive biomarker in EC. Further large-cohort studies are needed to confirm these findings.	esophagus
Minimally Invasive and Robotic Esophagectomy: A Review.	Great advances have been made in the surgical management of esophageal disease since the first description of esophageal resection in 1913. We are in the era of minimally invasive esophagectomy. The current three main approaches to an esophagectomy are the Ivor Lewis technique, McKeown technique, and the transhiatal approach to esophagectomy. These operations were associated with a high morbidity and mortality. The recent advances in minimally invasive surgical techniques have greatly improved the outcomes of these surgical procedures. This article reviews the literature and describes the various techniques available for performing minimally invasive esophagectomy and robot-assisted esophagectomies, the history behind the development of these techniques, the variations, and the contemporary outcomes after such procedures.	esophagus
Inhibition of MUC1-C regulates metabolism by AKT pathway in esophageal squamous cell carcinoma.	Esophageal squamous cell carcinoma (ESCC) is one of the most common digestive tumors worldwide. The Mucin 1 (MUC1) heterodimeric protein has been confirmed that is overexpressed in ESCC and induced adverse outcomes. However, the detailed mechanism(s) remained challenging. So, we investigated the relationship between MUC1-C and metabolism in ESCC cells. In the results, TP53-induced glycolysis and apoptosis regulator (TIGAR) was overexpressed and correlative with MUC1-C positively in ESCC tissue. Targeting MUC1-C inhibits AKT-mTORC-S6K1 signaling and blocks TIGAR translation. We found that the inhibitory effect of GO-203 on TIGAR was mediated by inhibition of AKT-mTOR-S6K1 pathway. The findings also demonstrated that the suppressive effect of GO-203 on TIGAR is related to the decrease of glutathione level, the increase of reactive oxygen species and the loss of mitochondrial transmembrane membrane potential. In xenograft tissues, GO-203 inhibited the growth of ESCC cells and lead to the low expression of transmembrane C-terminal subunit (MUC1-C) and TIGAR. This evidence supports the contention that MUC1-C is significant for metabolism in ESCC and indicated that MUC1-C is a potential target for the treatment of ESCC.	esophagus
Tracking significant modules and key genes for esophageal squamous cell carcinoma based on differential modules.	BACKGROUND: The exact molecular mechanism of esophageal squamous cell carcinoma (ESCC) is still unknown, and the prognosis of ESCC has not been significantly improved. OBJECTIVE: To understand the molecular mechanism of ESCC, differential modules (DMs) and key genes were identified through conducting analysis on the differential co-expression network (DCN) based on the gene expression profiles of ESCC and protein-protein interaction (PPI) data. MATERIALS AND METHODS: First, gene expression profiles of ESCC and PPI data recruiting and preprocessing were conducted; then, a DCN was constructed based on the gene co-expression and gene differential expression in ESCC; in the following, candidate DMs were mined from DCN through a systemic module searching strategy, and significance analysis was performed on candidate DMs to identify DMs; moreover, significant genes contained in the DMs were analyzed to identify the underlying biomarkers for ESCC. Finally, pathway enrichment analysis was conducted to disclose the function of these DMs. RESULTS: A total of 10,975 genes were obtained after comprehensively preprocessing on the gene expression profiles and PPI data. Then, a DCN with 915 nodes (1164 interactions) was built, and 45 seed genes were identified. In the following, four DMs that separately enriched in phenylalanine metabolism, nicotine addiction, phenylalanine metabolism, and B-cell receptor signaling pathway were identified, where module 1 and module 3 were all enriched in phenylalanine metabolism pathway. Furthermore, the most significant seed gene myeloperoxidase (MPO) was contained in all of the DMs. CONCLUSIONS: In this study, we successfully identified 4 DMs, three significant pathways, and a key gene MPO in ESCC, which might play key roles during the occurrence and development of ESCC and could be chosen as good indicators and therapeutic schedule for ESCC.	esophagus
Genetic, epigenetic and transcriptional comparison of esophagus tumor‑associated and adjacent normal myofibroblasts.	Myofibroblasts (MFs) are present in healthy tissues and are also key components of the tumor microenvironment. In the present study a comparative analysis of MFs obtained from various gastrointestinal tumor tissues and from tumor‑adjacent normal tissues of cancer patients was performed, with the aim to evaluate differences in MF morphology, gene expression profile and function. The goal was to correlate the observed morphological and functional variations with the underlying genetic and epigenetic backgrounds. The mutation frequency of MFs was assessed by next generation sequencing. The transcript levels of cancer‑specific genes were determined by TaqMan array and quantitative polymerase chain reaction. Epigenetic modifications were analyzed by immunocytochemistry and western blotting. The migratory capacity of MFs was assessed by scratch assay, whereas matrix metalloproteinase expression and activity were obtained by quantitative polymerase chain reaction and zymography. The results of the present study demonstrate that MFs were present in an increased number and with altered morphology in tumor samples compared with the healthy tissue. Although the detected number of mutations in tumor‑associated and normal tissue‑derived MFs did not differ markedly, shifts in the level of specific acetylated and methylated histone proteins, namely decreased levels of trimethylated H3K9 and acetylated H4K16 were demonstrated in tumor‑associated MFs. Transcript levels of several tumor‑specific genes involved in metastasis, regulation of cellular growth, apoptosis, as well as in hypoxia‑angiogenesis were altered in tumor‑derived MF cultures. Increased mRNA levels were obtained and activity of matrix metalloproteases in tumor‑derived MFs and these cells also exhibited a higher migratory capacity compared with the normal MFs. In summary, the results of the present study indicate that tumor‑associated MFs display an altered phenotype compared with healthy tissue derived counterparts. The results imply that epigenetic rather than genetic alterations are associated with the development of the distinct expressional and functional features, which define this MF phenotype in the tumor microenvironment.	esophagus
Association of preoperative inflammation-based prognostic score with survival in patients undergoing salvage esophagectomy.	Salvage esophagectomy (SALV) is potentially beneficial for patients with residual or relapsed esophageal carcinoma after definitive chemoradiotherapy (dCRT), although preoperatively identifying good candidates for SALV remains difficult. We investigated the prognostic impacts of inflammatory and nutritional status in patients undergoing SALV after dCRT. Forty-seven SALV patients were retrospectively reviewed, of whom 46 (98%) had squamous cell carcinoma and 1 (2%) adenocarcinoma. Possible prognostic factors included patients' demographic data, physical status, blood chemistry profiles, and clinical/pathological tumor features. The Glasgow prognostic score (GPS) was derived from preoperative C-reactive protein (CRP) and albumin values. Thirty (64%), 11 (23%), and 6 (13%) patients were classified into the GPS 0, 1, and 2, respectively, groups. None of the possible prognostic factors showed significant correlations with GPS. Patients with GPS 0 had better outcomes than those with GPS 1 or GPS 2 (Median survivals: 37.8, 15.9, and 5.1 months, respectively, P < 0.001). In the multivariable Cox proportional hazards model, GPS 1 (HR 5.62, 95% CI 1.94-16.4, P = 0.002), GPS 2 (HR 9.10, 95% CI 2.60-31.8, P < 0.001), R1/2 resection (HR 16.3, 95% CI 3.62-86.7, P < 0.001) and incomplete response to dCRT (HR 3.53, 95% CI 1.12-12.5, P = 0.03) were all independent risk factors for a poor outcome. Preoperative GPS is potentially useful for predicting outcomes in esophageal cancer patients undergoing SALV.	esophagus
Efficacy of Enteral Access in Patients with Esophageal Squamous Cell Carcinoma Under Neoadjuvant Therapy.	BACKGROUND: Enteral feeding tubes used to manage the nutritional status of esophageal cancer were evaluated regarding their effectiveness in patients receiving neoadjuvant therapy. PATIENTS AND METHODS: A retrospective study evaluating patients with esophageal squamous cell carcinoma undergoing neoadjuvant therapy between 2001 and 2014 was conducted at a medical center. Hospital patients' records for enteral access (EA) insertion and treatment outcomes were statistically analyzed. RESULTS: Patients with EA at initial diagnosis had lower body mass index than the group without EA (p=0.012). Chemotherapy-related adverse events with grade 3-4 mucositis were significantly less frequent in the EA group (p=0.008), and grade 3-4 anemia was significantly more frequent (p=0.012). The 4-year mortality rate was 63.0% in the EA group and 67.7% in the group without EA (p(non-inferiority)=0.035), which met the non-inferiority criterion with a non-inferiority margin of 10%. CONCLUSION: Patients with esophageal squamous cell carcinoma with malnutrition status undergoing neoadjuvant therapy with EA showed an improved outcome at maintaining nutritional status, reduced severity of mucositis and improved survival rate.	esophagus
Management of Pleural Effusion After Mediastinoscopic Radical Esophagectomy.	BACKGROUND/AIM: Trans-hiatal and -cervical approach mediastinoscopic radical esophagectomy (TMrE) for esophageal cancers is a less-invasive procedure and does not require for trans-thoracic approach management. However, some patients suffer from pleural effusion after TMrE. In the present study, we investigated the clinicopathological factors of patients needing drainage of pleural effusion (DPE) after TMrE. PATIENTS AND METHODS: This study included 118 patients who underwent TMrE between 2010 and 2016. RESULTS: There were 43, 34 and 41 patients that underwent none, a single, and two or more DPEs respectively. Left-side DPE was significantly more frequent compared to right-side DPE. Change in the C-reactive protein (CRP) levels after surgery was significantly higher in patients with multiple DPEs than patients with none or a single DPE. The hospitalization days were significantly longer for patients with multiple DPEs. CONCLUSION: Pleural effusion accumulates due to continuous inflammation. Although a temporary DPE is sometimes performed, post-operative chest drainage tubes are not necessarily needed.	esophagus
Focally amplified lncRNA on chromosome 1 regulates apoptosis of esophageal cancer cells via DRP1 and mitochondrial dynamics.	Long noncoding RNAs (lncRNAs), a family of noncoding RNA transcripts with a length of <200 nucleotides (nts), have been associated with the pathological development of various types of carcinogenesis. Focally amplified lncRNA on chromosome 1 (FAL1) is a recently identified lncRNA. In the current study, we aimed to investigate the physiological function of FAL1 in esophageal squamous cell carcinoma (ESCC). Our findings demonstrate that FAL1 was associated with esophageal cancer cell survival by regulating mitochondrial fission. First, we found that the expression of the mitochondrial fission protein dynamin-related protein 1 (DRP1) was significantly reduced, but the expression of the mitochondrial fusion protein mitofusin 1 (Mfn1) was increased in ESCC tissues and esophageal cancer cell lines as compared with adjacent normal tissues and a normal esophagus epithelial cell line. In addition, we found that reduced expression of DRP1 in the esophageal cancer cell lines KYSE450 and EC9706 cells was associated with increased expression of FAL1. Inhibition of FAL1 promoted mitochondrial fission and mitochondrial dysfunction in KYSE450 and EC9706 cells mediated by DRP1. Silencing of DRP1 abolished FAL1-induced apoptosis through a mitochondrial-dependent pathway. Our findings suggest that FAL1/DRP1 could be a therapeutic target for the treatment of ESCC. © 2018 IUBMB Life, 71(1):254-260, 2019.	esophagus
Prognostic significance of microsatellite-instability in gastric and gastroesophageal junction cancer patients undergoing neoadjuvant chemotherapy.	Perioperative systemic treatment is standard of care for Caucasian patients with locally advanced, resectable gastric adenocarcinoma. The prognostic relevance of the microsatellite instability (MSI) status in patients undergoing neoadjuvant chemotherapy followed by resection is unclear. We analyzed the association of the MSI status with histological regression and clinical outcome in patients undergoing neoadjuvant systemic treatment. Tumor tissue from patients undergoing neoadjuvant chemotherapy followed by resection for gastric or gastroesophageal-junction adenocarcinoma was analyzed for MSI status using a mononucleotide marker panel encompassing the markers BAT25, BAT26, and CAT25. Histological regression, relapse-free survival and overall survival were calculated and correlated with MSI status. We identified the MSI-H phenotype in 9 (8.9%) out of 101 analyzed tumors. Though a poor histological response was observed in eight out of nine MSI-H patients, overall survival was significantly better for patients with MSI-H compared to MSS tumors (median overall survival not reached vs. 38.6 months, log-rank test p = 0.014). Among MSI-H patients, an unexpected long-term survival after relapse was observed. Our data indicate that the MSI-H phenotype is a favorable prognostic marker in gastric cancer patients undergoing neoadjuvant treatment. The benefit of perioperative cytotoxic treatment in patients with MSI-H gastric cancer, however, remains questionable. Future trials should stratify patients according to their MSI status, and novel treatment modalities focusing on MSI-H tumors should be considered.	esophagus