crossing96/oncoscreening huggingface dataset:
Dual inhibition of cMET and EGFR by microRNA-338-5p suppresses metastasis of esophageal squamous cell carcinoma.	MicroRNAs, as a group of post-transcriptional regulators, regulate multiple pathological processes including metastasis during tumor development. Here, we demonstrated the metastasis-suppressive function of microRNA (miR)-338-5p in esophageal squamous cell carcinoma (ESCC). Overexpression of miR-338-5p had inhibitory effect on invasive ability of ESCC cells and extracellular matrix degradation, whereas silencing miR-338-5p had opposite effects. Mechanistically, miR-338-5p directly targeted the 3' untranslated regions of hepatocellular growth factor receptor cMet (cMET) and epidermal growth factor receptor (EGFR). As a result, miR-338-5p inhibited the downstream signaling cascades of cMET and EGFR and repressed cMET- and EGFR-mediated ESCC cell invasion. Re-expression of cMET or EGFR in miR-338-5p overexpressing ESCC cells was sufficient to derepress ESCC cell invasion both in vitro and in vivo. We further showed that such manipulation downregulated the expression and secretion of matrix metalloproteinases 2 and 9, which resulted in impaired extracellular matrix degradation and cell invasion. Most importantly, systemic delivery of miR-338-5p mimic significantly inhibited metastasis of ESCC cells in nude mice. Taken together, our results uncovered a previously unknown mechanism through which miR-338-5p suppresses ESCC invasion and metastasis by regulating cMET/EGFR-matrix metalloproteinase 2/9 axis and highlighted the potential significance of miR-338-5p-based therapy in treating patients with metastatic ESCC.	esophagus
Efficacy and safety of Kanglaite injection combined with chemotherapy for women breast cancer: A protocol for systematic review and meta-analysis of randomized clinical trials.	BACKGROUND: Breast cancer was the second cause of cancer death and approximately accounted for 30% of all newly diagnosed cancer in American women. Adjuvant chemotherapy is the preferred treatment approach for breast patients. Kanglaite injection (KI) was commonly used as adjuvant chemotherapy combined with chemotherapy for women breast cancer which could increase chemotherapy efficacy and alleviate chemotherapy drugs induced adverse events, however, the efficacy and safety for KI combined western medicine remains controversial. Thus, we conducted this protocol of systematic review and meta-analysis to estimate the efficacy and safety of KI combined with western medicine for women breast cancer. METHODS: This study will search electronic database included English medicals databases and Chinese databased up to May 2021. The main outcomes of this study include clinical efficacy rate. Adverse reaction rate, Karnofsky Performance Status and immune function were defined as the secondary outcomes. RESULTS: This protocol study will comprehensively evaluate the efficacy and safety of KI combined with chemotherapy for women breast cancer. CONCLUSION: This protocol for systematic review and meta-analysis will evaluate the efficacy and safety of KI combined with chemotherapy for women breast cancer, aiming to provide optimal therapy for women breast cancer patients.	esophagus
Additional Treatment Following Noncurative Endoscopic Resection for Esophageal Squamous Cell Carcinoma: A Comparison of Outcomes between Esophagectomy and Chemoradiotherapy.	BACKGROUND: Endoscopic resection (ER) has been widely implemented for cT1N0 esophageal squamous cell carcinoma (ESCC). Additional therapy, including esophagectomy and chemoradiotherapy (CRT), is sometimes required after noncurative ER. METHODS: We retrospectively reviewed 108 patients who received any additional treatment following noncurative ER (positive vertical margins, lymphovascular invasion, or invasion depth of submucosa or more), and compared the short- and long-term outcomes between the two treatment modalities. RESULTS: Of 108 patients, 56 underwent esophagectomy (E group), and 52 received CRT (CRT group). A positive vertical margin was observed in 17 (14.8%) patients and high risks of occult lymph node metastasis were observed in 91 (85.2%) patients, as well as lymphovascular invasion in 35 (32.4%) patients, invasion depth of the submucosa or more in 27 (25.0%) patients, and both in 29 (26.9%) patients. The E group patients were significantly younger (p = 0.046) and tended to present with larger tumors than those in the CRT group (p = 0.057). Lymphatic invasion was more frequent in the E group (p = 0.019), and, furthermore, one treatment-related death was observed in the E group. There were no significant differences between the groups in overall and disease-specific survival (p = 0.406 and 0.151, respectively), however, recurrence was only observed in the CRT group. CONCLUSION: Both esophagectomy and CRT are safe and effective as additional treatments after noncurative ER in patients with ESCC. Esophagectomy is oncologically safe, whereas a risk of postoperative morbidity and mortality remains. Although the adverse events are acceptable, CRT has a certain degree of risk of disease recurrence.	esophagus
Primary Esophageal Small Cell Carcinoma Masquerading as Non-Hodgkin Lymphoma in a Young Patient.	BACKGROUND/AIM: Small cell cancer of the esophagus (SCCE) is an extremely rare entity with an aggressive clinical course, thus early diagnosis and treatment are important for improved survival. CASE REPORT: A 35-year-old male presented with dysphagia, loss of appetite and weight loss. Diagnostic workup revealed an esophageal mass, which was diagnosed as primary non-Hodgkin lymphoma (NHL) on initial biopsy. Despite receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy for 3 months, there was an interval increase in the size of the esophagus mass, which unveiled underlying SCCE. A re-review of the previous biopsy specimen with immunohistochemical staining confirmed the initial diagnosis as SCCE as well. Despite 4 cycles of platinum-based chemotherapy and radiotherapy, the malignancy progressed and proved fatal. CONCLUSION: SCCE and non-Hodgkin lymphomas are rare entities, whose morphologies can be diagnostically challenging, hence they require special immunostaining for accurate diagnosis. Prompt diagnosis and initiation of treatment can confer better quality of life and survival.	esophagus
"""Tubeless"" esophagectomy: Less is more."	"The esophageal cancer surgery is a complex procedure with elevated rates of both morbidity and mortality, which is why, in order to achieve adequate results, it should be performed in high volume centers, where complete multidisciplinary support is available and recent clinical guidelines are applied. We describe the initial experience and the technique of ""tubeless"" esophagectomy where esophageal resection and mediastinal lymphadenectomy are performed and no drains nor tubes of any kind are placed, with the aim to decrease the level of surgical aggression, enhance the postoperative comfort and accelerate the patient́s recovery."	esophagus
Hypoxia induces chemoresistance of esophageal cancer cells to cisplatin through regulating the lncRNA-EMS/miR-758-3p/WTAP axis.	Hypoxia contributes significantly to the development of chemoresistance of many malignancies including esophageal cancer (EC). Accumulating studies have indicated that long non-coding RNAs play important roles in chemotherapy resistance. Here, we identified a novel lncRNA-EMS/miR-758-3p/WTAP axis that was involved in hypoxia-mediated chemoresistance to cisplatin in human EC. Hypoxia induced the expressions of lncRNA EMS and WTAP, and reduced the expression of miR-758-3p in EC cell line ECA-109. In addition, the expressions of EMS and WTAP were required for the hypoxia-induced drug resistance to cisplatin in EC cells, while overexpression of miR-758-3p reversed such chemoresistance. The targeting relationships between EMS and miR-758-3p, as well as miR-758-3p and WTAP, were verified by luciferase-based reporter assays and multiple quantitative assays after gene overexpression/knockdown. Moreover, we found significant correlations between tumor expressions of these molecules. Notably, higher levels of EMS/WTAP, or lower levels of miR-758-3p in tumors predicted worse survivals of EC patients. Furthermore, in a xenograft mouse model, targeted knockdown of EMS and WTAP in ECA-109 cells markedly attenuated the resistance of tumors to cisplatin treatments. Our study uncovers a critical lncRNA-EMS/miR-758-3p/WTAP axis in regulating hypoxia-mediated drug resistance to cisplatin in EC.	esophagus
The landscape and biological relevance of aberrant alternative splicing events in esophageal squamous cell carcinoma.	"Aberrant alternative splicing events (AASEs) are key biological processes for tumorigenesis and the rationale for designing splice-switching oligonucleotides (SSOs). However, the landscape of AASEs in esophageal squamous cell carcinoma (ESCC) remains unclear, which undermines the development of SSOs for ESCC. Here, we profiled AASEs based on 125 pairs of RNA-seq libraries. We identified 14,710 AASEs in ESCC, most of which (92.67%) affected coding genes. The first exon of transcripts was frequently changed in ESCC. We constructed a regulatory network where 74 RNA-binding proteins regulated 2142 AASEs. This network was enriched in apoptotic pathways and various adhesion/junction-related processes. Somatic mutations in ESCC regulating ASEs were mainly through trans-regulatory mode and were enriched in intron regions. Isoform switches of apoptotic genes and binding genes both tended to induce ""noncoding transcripts"" and ""domain loss,"" disrupting the apoptotic and Hippo signaling pathways. All ESCC samples were grouped into three clusters with different AASEs patterns and the second cluster was identified as ""cold tumor,"" with a low abundance of immune cells, activated immune pathways, and immunomodulators. Our work comprehensively profiled the landscape of AASEs in ESCC, revealed novel AASEs related to tumorigenesis and immune microenvironment, and suggested promising directions for designing SSOs for ESCC."	esophagus
HPV16 infection promotes an M2 macrophage phenotype to promote the invasion and metastasis of esophageal squamous cell carcinoma.	OBJECTIVES: High-risk human papillomavirus (HR-HPV) is an important risk factor for esophageal cancer. Macrophages constitute a crucial immune medium for regulating HPV-related tumors; however, the specific regulatory mechanisms remain unknown. Therefore, the purpose of our current study was to investigate the mechanism by which HPV16E6 regulates macrophages to promote the invasion and metastasis of esophageal cancer. METHODS: HPV16E6 infection was detected by polymerase chain reaction. Immunohistochemistry was used to verify the distribution of tumor-associated macrophages (TAMs) and MMP-9 expression in esophageal squamous cell carcinoma tissues (ESCCs), and cancer adjacent normal tissues (CANs) from Kazakh patients. ESCC cells were transfected with a plasmid over-expressing HPV16E6 and non-contact cocultured with macrophages. RESULTS: The infection rate of HPV16E6 in Kazakh ESCCs was clearly higher than that in CANs (P < 0.05). The density of CD163-positive TAMs was significantly positively correlated with HPV16E6 infection in ESCCs (P < 0.05). After coculturing macrophages and EC9706 cells transfected with the HPV16E6 plasmid, the phenotype of macrophages transformed into M2 macrophages. The migration and invasion ability of ESCC cells were higher in the HPV16E6-transfected and coculture group than in the HPV16E6 empty vector-transfected and non-cocultured HPV16E6-transfected groups (all P < 0.05). The density of M2-like TAMs in ESCCs was positively correlated with the level of MMP-9 expression. MMP-9 expression in the HPV16E6-ESCC coculture macrophages group was substantially higher than that in controls (all P < 0.05). CONCLUSIONS: HPV16 infection mediates tumor-associated macrophages to promote ESCC invasion and migration.	esophagus
Screening for synchronous esophageal second primary tumors in patients with head and neck cancer.	Patients with head and neck squamous cell carcinoma (HNSCC) have an increased risk of developing esophageal second primary tumors (ESPTs). We aimed to determine the incidence, stage, and outcome of synchronous ESPTs in patients with HNSCC in a Western population. We performed a prospective, observational, and cohort study. Patients diagnosed with HNSCC in the oropharynx, hypopharynx, any other sub-location in combination with alcohol abuse, or patients with two synchronous HNSCCs, between February 2019 and February 2020 underwent screening esophagogastroduodenoscopy (EGD). ESPT was defined as presence of esophageal squamous cell carcinoma (ESCC) or high grade dysplasia (HGD). Eighty-five patients were included. A lesion suspected for ESPT was detected in 14 of 85 patients, which was pathologically confirmed in five patients (1 ESCC and 4 HGD). The radiotherapy field was extended to the esophagus in two of five patients, HGD was treated with endoscopic resection in three of five patients. None of the ESPTs were detected on MRI and/or CT-scan prior to EGD. Of the remaining nine patients, three had low grade dysplasia on histology whereas the other six patients had benign lesions. Incidence of synchronous ESPT was 5.9% in our cohort of HNSCC patients. All ESPTs were diagnosed at an early stage and treated with curative intent. We recommend that screening for synchronous ESPTs should be considered in a selected group of patients with HNSCC.	esophagus
Metastatic Esophageal Carcinoma Cells Exhibit Reduced Adhesion Strength and Enhanced Thermogenesis.	Despite continuous improvements in multimodal therapeutic strategies, esophageal carcinoma maintains a high mortality rate. Metastases are a major life-limiting component; however, very little is known about why some tumors have high metastatic potential and others not. In this study, we investigated thermogenic activity and adhesion strength of primary tumor cells and corresponding metastatic cell lines derived from two patients with metastatic adenocarcinoma of the esophagus. We hypothesized that the increased metastatic potential of the metastatic cell lines correlates with higher thermogenic activity and decreased adhesion strength. Our data show that patient-derived metastatic esophageal tumor cells have a higher thermogenic profile as well as a decreased adhesion strength compared to their corresponding primary tumor cells. Using two paired esophageal carcinoma cell lines of primary tumor and lymph nodes makes the data unique. Both higher specific thermogenesis profile and decreased adhesion strength are associated with a higher metastatic potential. They are in congruence with the clinical patient presentation. Understanding these functional, biophysical properties of patient derived esophageal carcinoma cell lines will enable us to gain further insight into the mechanisms of metastatic potential of primary tumors and metastases. Microcalorimetric evaluation will furthermore allow for rapid assessment of new treatment options for primary tumor and metastases aimed at decreasing the metastatic potential.	esophagus
The Mechanisms for the Association of Cancer and Esophageal Dysmotility Disorders.	BACKGROUND: Achalasia and other esophageal dysmotility disorders mimicking achalasia can be associated with cancer. This study aimed to review the main mechanisms for which cancer may develop in esophageal dysmotility disorder patients. METHODS: A narrative review was performed. RESULTS: The mechanism for developing squamous cell carcinoma and adenocarcinoma are discussed. Besides, achalasia-like syndromes related to familial KIT-gene mutation and pseudoachalasia are discussed. CONCLUSIONS: Knowing the main mechanism for which achalasia can be related to cancer is essential for clinicians to conduct the proper investigation, surveillance, and treatment.	esophagus
Racial disparities in provider recommendation for esophagectomy for esophageal carcinoma.	BACKGROUND: Racial disparities currently exist for the utilization rate of esophagectomy for Black patients with operable esophageal carcinoma. METHODS: A total of 37 271 cases with the American Joint Committee on Cancer clinical stage I, II, and III esophageal carcinoma that were reported to the National Cancer Database were analyzed between 2004 and 2016. A multivariable-adjusted logistic regression model was used to evaluate differences in the odds ratio of esophagectomy not being recommended based on race. Kaplan-Meier curves and log-rank tests were used to evaluate differences in overall survival. Propensity score methodology with inverse probability of treatment weighting (IPTW) was used to balance baseline differences in patient demographics. RESULTS: After IPTW adjustment, we identified 30 552 White patients and 3529 Black patients with clinical stage I-III esophageal carcinoma. Black patients had three times greater odds of not being recommended for esophagectomy (odds ratio: 3.03, 95% confidence interval: 2.67-3.43, p < 0.0001) compared to White patients. Black patients demonstrated significantly worse 3- and 5-year overall survival rates compared to White patients (log-rank p < 0.0001). CONCLUSION: Black patients with clinical stage I-III esophageal cancer were significantly less likely to be recommended for esophagectomy even after adjusting for baseline demographic covariates compared to White patients.	esophagus
Knockdown of long non-coding RNA CCAT2 suppresses growth and metastasis of esophageal squamous cell carcinoma by inhibiting the β-catenin/WISP1 signaling pathway.	OBJECTIVE: Long non-coding RNA (lncRNA) colon cancer-associated transcript 2 (CCAT2) plays oncogenic roles in several cancers, including esophageal squamous cell carcinoma (ESCC). However, the specific mechanism of how CCAT2 influences ESCC tumorigenesis is still unknown. METHODS: Using RT-qPCR, the mRNA expression levels of CCAT2 in 33 paired ESCC and adjacent non-cancer tissues and cell lines were measured. Lentiviral vector sh-CCAT2 was designed and transfected into TE10 cells. CCK-8 and transwell assays were employed to detect the effects of CCAT2 knockdown on cell proliferation and invasion, respectively. RT-qPCR and western blots were used to detect the effects of CCAT2 knockdown. RESULTS: CCAT2 was overexpressed in ESCC tissues compared with corresponding adjacent tissues. CCAT2 knockdown could suppress cell proliferation and invasion in vitro. Furthermore, knockdown of CCAT2 could suppress the mRNA and protein levels of β-catenin and Wnt-induced-secreted-protein-1 (WISP1), as well as the mRNA levels of their downstream targets VEGF-A, MMP2, and ICAM-1. High expression of CCAT2 and WISP1 were associated with poor prognosis of ESCC patients. CONCLUSIONS: In conclusion, a novel CCAT2/β-catenin/WISP1 axis was revealed in ESCC progression and may provide a promising therapeutic target against ESCC. CCAT2 and WISP1 are potential molecular biomarkers for predicting prognosis of ESCC.	esophagus
Comprehensive Analysis of PD-L1 Expression, Immune Infiltrates, and m6A RNA Methylation Regulators in Esophageal Squamous Cell Carcinoma.	BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common cancer types and represents a threat to global public health. N6-Methyladenosine (m6A) methylation plays a key role in the occurrence and development of many tumors, but there are still few studies investigating ESCC. This study attempts to construct a prognostic signature of ESCC based on m6A RNA methylation regulators and to explore the potential association of these regulators with the tumor immune microenvironment (TIME). METHODS: The transcriptome sequencing data and clinical information of 20 m6A RNA methylation regulators in 453 patients with ESCC (The Cancer Genome Atlas [TCGA] cohort, n = 95; Gene Expression Omnibus [GEO] cohort, n = 358) were obtained. The differing expression levels of m6A regulators between ESCC and normal tissue were evaluated. Based on the expression of these regulators, consensus clustering was performed to investigate different ESCC clusters. PD-L1 expression, immune score, immune cell infiltration and potential mechanisms among different clusters were examined. LASSO Cox regression analysis was utilized to obtain a prognostic signature based on m6A RNA methylation modulators. The relationship between the risk score based on the prognostic signature and the TIME of ESCC patients was studied in detail. RESULTS: Six m6A regulators (METTL3, WTAP, IGF2BP3, YTHDF1, HNRNPA2B1 and HNRNPC) were observed to be significantly highly expressed in ESCC tissues. Two molecular subtypes (clusters 1/2) were determined by consensus clustering of 20 m6A modulators. The expression level of PD-L1 in ESCC tissues increased significantly and was significantly negatively correlated with the expression levels of YTHDF2, METL14 and KIAA1429. The immune score, CD8 T cells, resting mast cells, and regulatory T cells (Tregs) in cluster 2 were significantly increased. Gene set enrichment analysis (GSEA) shows that this cluster involves multiple hallmark pathways. We constructed a five-gene prognostic signature based on m6A RNA methylation, and the risk score based on the prognostic signature was determined to be an independent prognostic indicator of ESCC. More importantly, the prognostic value of the prognostic signature was verified using another independent cohort. m6A regulators are related to TIME, and their copy-number alterations will dynamically affect the number of tumor-infiltrating immune cells. CONCLUSION: Our study established a strong prognostic signature based on m6A RNA methylation regulators; this signature was able to accurately predict the prognosis of ESCC patients. The m6A methylation regulator may be a key mediator of PD-L1 expression and immune cell infiltration and may strongly affect the TIME of ESCC.	esophagus
Techniques of Esophageal Anastomoses for Esophagectomy.	This article discusses and illustrates a variety of accepted techniques of esophagogastric anastomosis during an esophagectomy. The performance of an anastomotic technique can be surgeon specific, although it is of great benefit for the esophageal surgeon to be facile and adept in multiple techniques, as occasionally the clinical situation may be better suited for a particular technique. Regardless of the method of creating the esophagogastric anastomosis, the goal is to create a viable, tension-free and nonobstructive anastomosis with adequate margins.	esophagus
Chemoradiation Therapy as Definitive Treatment of Esophageal Cancer.	Definitive chemoradiation therapy avoids the perioperative and long-term morbidity of esophagectomy and is the standard of care for cervical esophageal cancer. There are significant differences in tumor response to chemoradiation and recurrence patterns between squamous cell cancer and adenocarcinoma of the esophagus. Multimodality therapy for esophageal cancer continues to progress, now with the widespread use of PET scanning and possible active surveillance in patients with complete clinical response to chemoradiation. As drug development and targeted therapy trials continue to expand, our understanding of tumor biology and precision medicine will continue to refine the treatment of esophageal cancer.	esophagus