crossing96/oncoscreening huggingface dataset:
The prognostic and clinicopathologic characteristics of CD147 and esophagus cancer: A meta-analysis.	OBJECTIVE: The prognostic significance of CD147 expression in esophageal cancer patients remains controversial. Using a meta-analysis, we investigated the prognostic and clinicopathologic characteristics of CD147 in esophageal cancer. METHODS: A comprehensive literature search of the PubMed (1966-2016), EMBASE (1980-2016), Cochrane Library (1996-2016), Web of Science (1945-2016), China National Knowledge Infrastructure (1982-2016), and Wanfang databases (1988-2016) was performed to identify studies of all esophageal cancer subtypes. Correlations between CD147 expression and survival outcomes and clinicopathological features were analyzed using meta-analysis methods. RESULTS: Seventeen studies were included. High CD147 expression reduced the 3-year survival rate (OR = 3.26, 95% CI = (1.53, 6.93), p = 0.02) and 5-year survival rate(OR = 4.35, 95% CI = (2.13, 8.90), p < 0.0001). High CD147 expression reduced overall survival in esophageal cancer (HR = 1.60, 95% CI = (1.19, 2.15), p = 0.02). Additionally, higher CD147 expression was detected in esophageal cancer tissues than noncancerous tissues (OR = 9.45, 95% CI = (5.39, 16.59), p < 0.00001), normal tissues (OR = 12.73, 95% CI = (3.49, 46.46), p = 0.0001), para-carcinoma tissues (OR = 12.80, 95% CI = (6.57, 24.92), p < 0.00001), and hyperplastic tissues (OR = 3.27, 95% CI = (1.47, 7.29), p = 0.004). CD147 expression was associated with TNM stage (OR = 3.66, 95% CI = (2.20, 6.09), p < 0.00001), tumor depth (OR = 7.97, 95% CI = (4.13, 15.38), p < 0.00001), and lymph node status (OR = 5.14, 95% CI = (2.03,13.01), p = 0.0005), but not with tumor differentiation, age, or sex. CONCLUSION: Our meta-analysis suggests that CD147 is an efficient prognostic factor in esophageal cancer. High CD147 expression in patients with esophageal cancer was associated with worse survival outcomes and common clinicopathological indicators of poor prognosis.	esophagus
Overuse of Repeat Upper Endoscopy in the Veterans Health Administration: A Retrospective Analysis.	OBJECTIVES: Americans undergo ∼7 million esophagogastroduodenoscopies (EGDs) annually, and one-third of Medicare beneficiaries undergo a repeat EGD within 3 years. As many as 43% of these repeat EGDs are inappropriate. We aimed to determine the rate of repeat inappropriate EGD within the Veterans Health Administration (VHA), and identify factors associated with repeat EGD. METHODS: We conducted retrospective analyses of Veterans undergoing an index EGD at 159 VHA facilities between 1 January 2003 and 30 June 2007. We excluded Veterans without regular use of VHA for health care or 5 years of follow-up. Appropriateness of repeat EGDs was classified based on diagnostic and procedure codes into three categories: Likely Appropriate, Possible Overuse, and Probable Overuse. The proportion of repeat EGDs in each category was tabulated. Multilevel logistic regression was performed to estimate the impact of patient-level and site-level factors on the odds of repeat EGD. RESULTS: Of the 235,855 included Veterans, 85,690 (36.3%) underwent a repeat EGD within 5 years. Of the repeat EGDs, 42,412 (49.5%) were Likely Appropriate, 35,503 (41.4%) represented Possible Overuse, and 7,756 (9.1%) represented Probable Overuse. Patients with more frequent encounters with primary care providers and access to facilities performing EGD and with greater complexity of services were more likely to receive repeat EGD, regardless of whether the repeat EGD was appropriate or overuse. Women were slightly more likely to undergo repeat EGD in Probable Overuse situations. CONCLUSIONS: Overuse of repeat EGD is common in VHA despite the absence of financial incentives that promote overuse. Efforts are needed to better understand the motivations for overuse and barriers to appropriate use, and to promote appropriate use of repeat EGD.	esophagus
Somatic mutations in ZFHX4 gene are associated with poor overall survival of Chinese esophageal squamous cell carcinoma patients.	Recent genome-sequencing studies have revealed dozens of genes frequently mutated in esophageal squamous cell carcinoma, but few genes are associated with patients' clinical outcomes. Novel prognostic biomarkers are urgently needed in the clinic. We collected both somatic mutations and clinical information of 442 Chinese esophageal squamous cell carcinoma patients from four published studies. Survival analysis was performed to reveal the clinical significance of the mutated genes. Dysregulation of the mutated genes was observed from public gene-expression data sets and its effects on cell migration and invasion were investigated with siRNA-mediated silencing. Our integrated analysis revealed 26 genes significantly and frequently mutated in esophageal squamous cell carcinoma. Importantly, mutations in ZFHX4, SPHKAP, NRXN1, KIAA1109, DNAH5 and KCNH7 were associated with poor survival. In addition, ZFHX4 was overexpressed in tumor tissues compared to normal controls, and knockdown of ZFHX4 in vitro significantly inhibited cell migration and invasion. Mutations in ZFHX4 were strongly associated with poor prognosis and the down-regulation of ZFHX4 inhibits the progression of esophageal squamous cell carcinoma. Further investigation is warranted to confirm the prognostic values of ZFHX4 in a prospective study.	esophagus
Altered expression of lysosomal associated membrane protein 1 in esophageal squamous cell carcinoma.	BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers. LAMP1, major protein components of lysosome, is primarily located on the lysosomal membrane and rarely expressed on the surface of normal cells, playing an important role in the lysosome-mediated physiological processes. Previous studies confirmed that LAMP1 showed high expression in astrocytoma. The purpose of this study was to investigate the expression levels of LAMP1 and to discuss its roles in ESCC. METHODS: We collected 610 tissue samples of ESCC patients to construct tissue microarrays, which were subsequently stained by immunohistochemistry with LAMP1 antibody. RESULTS: After immunohistochemical staining, a total of 584 patients, including 453 men and 131 women, were analysed. The positive immunostaining was mainly located at the cytoplasm. The LAMP1 expression levels were significantly different between different T status (P<0.001), TNM stages (P<0.01) and degrees of tumor histological differentiation (P<0.001). Besides, LAMP1 expression levels were positively correlated with TNM stages (P<0.05). The higher the TNM stages, the higher the LAMP1 expression levels. Similar results also appeared in degrees of tumor histological differentiation (P<0.01), but not in ages, genders, tumor size, T status, lymphatic metastasis and tumor locations (P>0.05). CONCLUSION: LAMP1 is involved in the TNM stages and histological differentiation of the ESCC. Targeted therapy for LAMP1 may be a promising novel therapeutic strategy against poorly differentiated ESCC.	esophagus
Post-trimodality expression levels of metadherin (MTDH) as a prognostic biomarker for esophageal adenocarcinoma patients.	Resectable esophageal adenocarcinoma (EAC) patients often receive chemoradiation followed by surgery. However, most patients experience recurrences. Overexpression of MTDH, an oncoprotein with multiple functions, has been found to be associated with poor prognosis in breast cancer, glioblastoma, melanoma and various gastrointestinal malignancies, but not in EAC. We sought to establish its role in resistant EAC (post-treatment residual EAC). MTDH was assessed by immunohistochemistry in resected EAC, and results were correlated with clinical outcomes. MTDH expression was detectable in 72.5% (50/69) of patients, while expression levels were high (positive) in 50.7% (35/69). Of 69 patients analyzed, 25 had no relapse and 44 patients had a relapse (8 with local-regional and 36 with distant). The median follow-up duration was 3 years (0.4-11.6). The median overall survival was not associated with MTDH status (2.79 years for MTDH-negative and 3.60 years for MTDH-positive patients, p = 0.121). In addition, MTDH was not associated with either the type of relapse (local or distant), baseline clinical stage, tumor grade, presence of signet ring cells, surgical (yp) stage, percentage of residual EAC or presence of lymphovascular invasion. Our data reveal that MTDH is not a prognostic biomarker in resistant EAC after trimodality therapy.	esophagus
Node-Negative Esophageal Cancer With Short-Interval Isolated Metastasis to the Gallbladder: A Case Report.	A 55 year old male smoker presented with clinical T3N0 esophageal adenocarcinoma of the GE junction. He completed neoadjuvant chemoradiotherapy with carboplatin/paclitaxel and 5040cGy of radiation. He had limited clinical response on restaging but no evidence of metastatic disease and completed a minimally invasive three field esophagectomy. This was complicated by a chyle leak requiring thoracic duct embolization from which he recovered well. Surgical pathology showed no apparent nodal disease or metastases but a poorly differentiated primary tumor with signet-cell features. Approximately 3 months after his surgery, he developed right upper quadrant abdominal pain and elevated liver function tests and was taken for laparoscopic cholecystectomy. Gallbladder pathology demonstrated poorly differentiated adenocarcinoma with extensive lymphovascular invasion with immunohistochemistry analysis and comparison with the original surgical specimen confirming metastatic adenocarcinoma of esophageal origin. Literature review suggests that signet cell features and limited response to neoadjuvant therapy point to a more aggressive biology in esophageal cancer and increase the risk of metastatic disease, even in the setting of node negativity.	esophagus
MicroRNA and target mRNA selection through invasion and cytotoxicity cell modeling and bioinformatics approaches in esophageal squamous cell carcinoma.	This study analyzed microRNA (miRNA) and mRNA expression profiles and investigated the biological characteristics of ESCC by using invasion and cytotoxicity cell models. miRNA profiles were evaluated through miRNA microarray. Transwell chamber and nedaplatin (NDP) were used to construct invasion and cytotoxicity cell models. Invasion Transwell and cytotoxicity assays were performed to examine the invasiveness and proliferation in the cell models. Functional miRNAs were selected from dysregulated miRNAs through qRT-PCR. Biometric Research Program (BRB)-array tools, Cytoscape plugins, and DAVID were utilized to find potential mRNAs targeted by these two miRNAs between ESCC and paired normal adjacent tissues. Our microarray obtained 11 dysregulated miRNAs expressed in three paired ESCC samples from Kazakhs (ethnicity in Northwestern China). qRT-PCR demonstrated the miRNA expression in the invasion and cytotoxicity cell models. miR‑652-5p and miR‑21‑5p exhibited a consistent expression level in the microarray and cell models. Bioinformatics revealed that the potential targets of PLD1, MSH2, STC1, and DSG1 might be involved in ESCC invasion and proliferation. Cell models with bioinformatics approaches may help distinguish functional genes. miR‑652-5p, miR‑21‑5p, and their potential target genes may participate in ESCC development and metastasis.	esophagus
Clonality analysis of synchronous gastro-oesophageal junction carcinoma and distal gastric cancer by whole-exome sequencing.	Gastro-oesophageal junction (GEJ) carcinoma and distal gastric cancer (GC) have distinct epidemiology and clinical features and their relationship is uncertain. Synchronous multiple gastric cancers located mostly at proximal and distal sites provide rare specimens for investigating the comprehensive genomic relationships among these cancers in the context of identical genetic circumstances. Formalin-fixed, paraffin-embedded (FFPE) samples from 12 patients with synchronous GEJ carcinoma and distal GC were collected in this study. Whole-exome sequencing (WES) was performed using normal tissues as a control. Mutational profiling, clonality analysis, a detailed clinico-pathological review, determination of MSI status, EBER in situ hybridization (ISH), and programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) immunohistochemical staining were performed. Twenty-three of the 24 samples were microsatellite-stable (MSS). Subclonal analysis revealed that nine pairs of GEJ and distal GC tumours in neoadjuvant chemotherapy naïve patients developed independently from different origins. Two patients who received neoadjuvant chemotherapy shared clonal origins with highly similar somatic alterations. The remaining one patient who shared a rare mutation died within 6.2 months at the N3 stage. However, the enriched pathway identified from the overall mutation spectra in distal GC and GEJ carcinoma showed the close relationship of these cancers. Thus, although these cancers may have similar characteristics, histopathological and genetic profiling from single tumour specimens may still underestimate the mutational burden and somatic heterogeneity of multiple GCs. In addition, this series of cases also showed a PD-L1 expression rate of 58.3% and 66.7% in distal GC and GEJ carcinoma, respectively, with all the cases expressing PD-1. This result suggests the potential benefit of immunotherapeutic treatments. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.	esophagus
Clinical Outcomes of Resectable Esophageal Cancer with Supraclavicular Lymph Node Metastases Treated with Curative Intent.	BACKGROUND: In the seventh edition of the Union for International Cancer Control (UICC) TNM classification, supraclavicular lymph node (SCLN) in regard to thoracic esophageal cancer (EC) is regarded as a distant organ, therefore, if resectable, SCLN metastasis is considered a candidate for systemic chemotherapy. The purpose of this study was to clarify the survival outcome in patients with resectable thoracic EC with SCLN metastases (M1LYM) treated with curative intent. PATIENTS AND METHODS: Clinical outcomes in patients with resectable thoracic EC with SCLN metastases (M1LYM) treated by esophagectomy or definitive chemoradiotherapy (dCRT) were retrospectively analyzed. RESULTS: A total of 102 patients were divided in three groups: Surgery with perioperative therapy, n=45; surgery alone, n=19; and dCRT, n=38. Overall, median progression-free survival and median survival time were 9.3 and 26.7 months, respectively. The median survival time was 27.5 months in the group treated with surgery with perioperative treatment, 50.6 months in those treated with surgery alone, and 22 months in the dCRT group. No significant survival difference was seen among the three groups. CONCLUSION: Over 30% of patients with resectable M1LYM treated with curative intent achieved long-term survival.	esophagus
Neoadjuvant chemotherapy or chemoradiation for patients with advanced adenocarcinoma of the oesophagus? A propensity score-matched study.	BACKGROUND: Multimodal therapies are the standard of care for advanced adenocarcinomas of the oesophagus and gastro-oesophageal junction (AEG Types I and II). Only three randomised trials have compared preoperative chemotherapy with and without radiation. The results showed a small benefit for combined chemoradiation. In the meantime, newer therapy protocols are available. AIM: In a propensity-score matched study, we analysed patients with locally advanced AEG type I or II, treated with chemotherapy (FLOT-protocol) or chemoradiation (CROSS-protocol), followed by oesophagectomy, in a single high-volume centre. PATIENTS AND METHODS: Between 2011 and 2015, 137 patients with advanced (cT3NxcM0) adenocarcinoma received pre-operative therapy; 70% had chemoradiation (CROSS-protocol) and 30% had chemotherapy (FLOT-protocol). After propensity-score matching, 40 patients from the CROSS-group were selected for analysis. Postoperative histopathological response and prognosis were analysed. RESULTS: The two groups were comparable according to the matching criteria age, gender, tumour location, and year of surgery. R0-resection was achieved in 97% of patients in the CROSS-group and 85% of the FLOT-group (p = 0.049). Major response of the primary tumour was evident more often in the CROSS-group (17/40 pts. 43%) versus FLOT-group (11/40 pts. 27%) as well no lymph node metastasis (ypN0 = 68% versus ypN0 = 40%) (p = 0.014). Prognosis were not significantly different between the two groups. In multivariate analysis, only ypN-category was an independent prognostic factor. CONCLUSION: Compared to FLOT-chemotherapy, neoadjuvant chemoradiotherapy with the CROSS-protocol in locally advanced adenocarcinoma AEG types I and II resulted in better response by the primary tumour and less lymph node metastasis but without superior survival.	esophagus
Comparative Quantitative Lymph Node Assessment in Localized Esophageal Cancer Patients After R0 Resection With and Without Neoadjuvant Chemoradiation Therapy.	INTRODUCTION: The effects of neoadjuvant chemoradiation therapy on lymph node retrieval during esophagectomy for patients with esophageal cancer are unclear. The aim of this study was to quantify lymph node retrieval after R0 esophagectomy and to assess its impact on overall survival in induction therapy patients. METHODS: One hundred seventy-four consecutive patients underwent esophagectomy with or without induction therapy from 2008 to 2015 for esophageal cancer. Total lymph nodes, positive lymph nodes, and lymph node ratios were compared between two groups of patients: those treated with either upfront surgery or those treated with neoadjuvant chemoradiation therapy followed by surgery. Comparisons were made using Student's t test. Overall survival was obtained and compared using Kaplan Meier survival curves. RESULTS: Total lymph node counts were less in the induction therapy group (p = 0.027), while positive lymph node counts and lymph node ratios did not differ between groups (p = 0.262 and p = 0.310, respectively). In the neoadjuvant chemoradiation followed by surgery group, overall survival was significantly shorter for patients who had any positive lymph nodes in the pathologic specimen (p = 0.0065). CONCLUSIONS: Total lymph node counts were significantly lower in the induction therapy group, while positive lymph node counts and lymph node ratios did not differ from the upfront surgery group. Although overall survival was not different between groups, it was decreased within the induction therapy cohort among those who had any positive lymph nodes retrieved at surgery. This study confirms that unstratified gross lymph node counts do not substantially relate to prognosis in the heterogeneous population of locally advanced esophageal cancer patients who may or may not have had neoadjuvant chemoradiation.	esophagus
Regulation of SPOCK1 by dual strands of pre-miR-150 inhibit cancer cell migration and invasion in esophageal squamous cell carcinoma.	Analysis of our microRNA (miRNA) expression signatures of human cancers based on RNA sequencing have shown that both strands of pre-miR-150, miR-150-5p (the guide strand) and miR-150-3p (the passenger strand), are significantly reduced in cancer tissues. We have investigated the functional significance of both strands of pre-miR-150 in cancer cells. The aim of this study was to investigate the antitumor function of these miRNAs and how these miRNAs regulated oncogenic targets in esophageal squamous cell carcinoma (ESCC). Ectopic expression studies demonstrated that both strands of pre-miR-150 miRNA inhibited ESCC cancer cell migration and invasion, indicating that both miR-150-5p and miR-150-3p acted as antitumor miRNAs. A combination of genome-wide gene expression analyses and in silico database searches showed that SPOCK1 (SPARC/osteonectin, cwcv and kazal-like domains proteoglycan 1) was a candidate target of miR-150-5p and miR-150-3p in ESCC cells. Luciferase reporter assays showed that SPOCK1 was directly regulated by these miRNAs. Silencing of SPOCK1 by small interfering RNA inhibited cancer cell migration and invasion. Overexpression of SPOCK1/SPOCK1 was confirmed by real-time PCR methods and immunohistochemistry. Taken together, downregulation of both strands of pre-miR-150 and overexpression of SPOCK1 are involved in ESCC pathogenesis. The involvement of passenger strand miRNAs in the regulation of cancer cell aggressiveness is a novel concept in RNA research.	esophagus
miR612 is associated with esophageal squamous cell carcinoma development and metastasis, mediated through TP53.	MicroRNAs (miRNAs) serve an important role in the regulation of gene expression. In the present study, differential expressions of miRNAs were compared between esophageal squamous cell carcinoma (ESCC) tissues and normal esophageal tissues. In combination with miRNA target prediction databases, a significantly increased expression of miR‑612 was discovered in ESCC. The relationship between miR‑612 and TP53 gene expression and their roles in ESCC invasion and metastasis was further studied by reverse transcription‑quantitative polymerase chain reaction and western blotting in EC109 cells and cancer tissues. The EC109 cell invasion and migration were significantly reduced after miR‑612 expression was inhibited. The levels of wild type TP53 protein and mRNA were lower in ESCC tissues compared to the normal esophageal epithelium. In addition, the mRNA and protein expression levels were reported as downregulated further in tumors with metastasis than in tumors without. In conclusion, miR‑612 is identified as associated with ESCC development and metastasis, likely through the regulation of TP53 expression, which could be a potential therapeutic target.	esophagus
Comparison of DVH-based plan verification methods for VMAT: ArcCHECK-3DVH system and dynalog-based dose reconstruction.	The purpose of this study was comparing dose-volume histogram (DVH)-based plan verification methods for volumetric modulated arc therapy (VMAT) pretreatment QA. We evaluated two 3D dose reconstruction systems: ArcCHECK-3DVH system (Sun Nuclear corp.) and Varian dynalog-based dose reconstruction (DBDR) system, developed in-house. Fifteen prostate cancer patients (67.6 Gy/26 Fr), four head and neck cancer patient (66 Gy/33 Fr), and four esophagus cancer patients (60 Gy/30 Fr) treated with VMAT were studied. First, ArcCHECK measurement was performed on all plans; simultaneously, the Varian dynalog data sets that contained the actual delivered parameters (leaf positions, gantry angles, and cumulative MUs) were acquired from the Linac control system. Thereafter, the delivered 3D patient dose was reconstructed by 3DVH software (two different calculating modes were used: High Sensitivity (3DVH-HS) and Normal Sensitivity (3DVH-NS)) and in-house DBDR system. We evaluated the differences between the TPS-calculated dose and the reconstructed dose using 3D gamma passing rates and DVH dose index analysis. The average 3D gamma passing rates (3%/3 mm) between the TPS-calculated dose and the reconstructed dose were 99.1 ± 0.6%, 99.7 ± 0.3%, and 100.0 ± 0.1% for 3DVH-HS, 3DVH-NS, and DBDR, respectively. For the prostate cases, the average differences between the TPS-calculated dose and reconstructed dose in the PTV mean dose were 1.52 ± 0.50%, -0.14 ± 0.55%, and -0.03 ± 0.07% for 3DVH-HS, 3DVH-NS, and DBDR, respectively. For the head and neck and esophagus cases, the dose difference to the TPS-calculated dose caused by an effect of heterogeneity was more apparent under the 3DVH dose reconstruction than the DBDR. Although with some residual dose reconstruction errors, these dose reconstruction methods can be clinically used as effective tools for DVH-based QA for VMAT delivery.	esophagus