Global burden of esophageal cancer attributable to high BMI in 204 countries and territories: 1990-2019.

BACKGROUND: Esophageal cancer (EC), a common and fatal disease, includes two histological subtypes; esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (ECA). To aid policymakers in the allocation of resources for the prevention and treatment of EC, updated data on EC deaths and disability-adjusted life years (DALYs) attributable to high body mass index (BMI) are necessary. The objective of this study was to identify trends in EC associated with high BMI between 1990 and 2019 using 2019 Global Burden of Disease data. METHODS: In this observational population-based study, epidemiological data on the association between high BMI and EC were obtained from GBD 2019. The age-standardized mortality rate (ASMRs) and disability-adjusted life year rate (ASDRs) attributable to high BMI-related EC were stratified by year, age, country, and sociodemographic index (SDI). The estimated annual percentage change (EAPC) was calculated to evaluate the temporal trends of the ASMRs and ASDRs between 1990 and 2019. RESULTS: In 2019, the proportion of EC deaths and DALYs attributed to high BMI was 18.1% and 18.9%, respectively, resulting in 89 904 (95% confidence interval [CI]: 27 879-171 255) deaths and 2 202 314 (95% CI: 681 901-4 173 080) DALYs. High BMI-related deaths and DALYs showed a strong upward trend, increasing by more than two-fold since 1990. East Asia and Western Europe showed the highest risk of EC mortality and DALYs attributable to high BMI; China and the USA bear the greatest burden. The ASMR and ASDR increased in five SDI regions. CONCLUSIONS: The incidence of EC is increasing, particularly in developing nations, which may be attributed to the prevalence of high BMI. To mitigate the impact of high BMI on the incidence of EC, it is important to increase awareness of its deleterious effects, which may alleviate the burden of this disease.

Perioperative Toripalimab Plus Chemotherapy for Patients With Resectable Non-Small Cell Lung Cancer: The Neotorch Randomized Clinical Trial.

Importance: Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown. Objective: To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone. Design, Setting, and Participants: This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The data cutoff date for this interim analysis was November 30, 2022. Interventions: Patients were randomized in a 1:1 ratio to receive 240 mg of toripalimab or placebo once every 3 weeks combined with platinum-based chemotherapy for 3 cycles before surgery and 1 cycle after surgery, followed by toripalimab only (240 mg) or placebo once every 3 weeks for up to 13 cycles. Main Outcomes and Measures: The primary outcomes were event-free survival (assessed by the investigators) and the major pathological response rate (assessed by blinded, independent pathological review). The secondary outcomes included the pathological complete response rate (assessed by blinded, independent pathological review) and adverse events. Results: Of the 501 patients randomized, 404 had stage III NSCLC (202 in the toripalimab + chemotherapy group and 202 in the placebo + chemotherapy group) and 97 had stage II NSCLC and were excluded from this interim analysis. The median age was 62 years (IQR, 56-65 years), 92% of patients were male, and the median follow-up was 18.3 months (IQR, 12.7-22.5 months). For the primary outcome of event-free survival, the median length was not estimable (95% CI, 24.4 months-not estimable) in the toripalimab group compared with 15.1 months (95% CI, 10.6-21.9 months) in the placebo group (hazard ratio, 0.40 [95% CI, 0.28-0.57], P < .001). The major pathological response rate (another primary outcome) was 48.5% (95% CI, 41.4%-55.6%) in the toripalimab group compared with 8.4% (95% CI, 5.0%-13.1%) in the placebo group (between-group difference, 40.2% [95% CI, 32.2%-48.1%], P < .001). The pathological complete response rate (secondary outcome) was 24.8% (95% CI, 19.0%-31.3%) in the toripalimab group compared with 1.0% (95% CI, 0.1%-3.5%) in the placebo group (between-group difference, 23.7% [95% CI, 17.6%-29.8%]). The incidence of immune-related adverse events occurred more frequently in the toripalimab group. No unexpected treatment-related toxic effects were identified. The incidence of grade 3 or higher adverse events, fatal adverse events, and adverse events leading to discontinuation of treatment were comparable between the groups. Conclusions and Relevance: The addition of toripalimab to perioperative chemotherapy led to a significant improvement in event-free survival for patients with resectable stage III NSCLC and this treatment strategy had a manageable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT04158440.

Plasma cell-free DNA 5-hydroxymethylcytosine and whole-genome sequencing signatures for early detection of esophageal cancer.

Esophageal cancer is a highly incidence and deadly disease with a poor prognosis, especially in developing countries. Owing to the lack of specific symptoms and early diagnostic biomarkers, most patients are diagnosed with advanced disease, leading to a 5-year survival rate of less than 15%. Early (n = 50) and middle-advanced (n = 50) esophageal squamous cell carcinoma (ESCC) patients, as well as 71 healthy individuals, underwent 5-hydroxymethylcytosine (5hmC) sequencing on their plasma cell-free DNA (cfDNA). A Northern Chinese cohort of cfDNA 5hmC dataset of 150 ESCC patients and 183 healthy individuals were downloaded for validation. A diagnostic model was developed using cfDNA 5hmC signatures and then improved by low-pass whole genome sequencing (WGS) features of cfDNA. Conserved cfDNA 5hmC modification motifs were observed in the two independent ESCC cohorts. The diagnostic model with 5hmC features achieved an AUC of 0.810 and 0.862 in the Southern and Northern cohorts, respectively, with sensitivities of 69.3-74.3% and specificities of 82.4-90.7%. The performance was well maintained in Stage I to Stage IV, with accuracy of 70-100%, but low in Stage 0, 33.3%. Low-pass WGS of cfDNA improved the AUC to 0.934 with a sensitivity of 82.4%, a specificity of 88.2%, and an accuracy of 84.3%, particularly significantly in Stage 0, with an accuracy up to 80%. 5hmC and WGS could efficiently differentiate very early ESCC from healthy individuals. These findings imply a non-invasive and convenient method for ESCC detection when clinical treatments are available and may eventually prolong survival.

Inhibition of BPHL inhibits proliferation in lung carcinoma cell lines.

Background: Lung cancer is one of the most common human malignant tumors and the leading cause of cancer death worldwide. Biphenyl hydrolase-like (BPHL) is a gene encoding the human BPHL enzyme, a serine hydrolase that catalyzes the hydrolytic activation of amino acid ester prodrugs of nucleoside analogs such as valacyclovir and valganciclovir. However, the role of BPHL in lung cancer is still unknown. Methods: In this study, we assessed the effect BPHL knockdown on the proliferation, apoptosis, colony formation, metastasis, and cell cycle of cancer cells. BPHL knockdown NCI-H1299 and A549 cells demonstrated decreased proliferation, as measured by Celigo cell counting. The MTT assay results were consistent with Celigo cell counting. Caspase 3/7 activity increased significantly in the NCI-H1299 and A549 cells after shBPHL knockdown. Decreased colony formation in the NCI-H1299 and A54 cells after shBPHL knockdown, as measured by crystal violet staining. Transmigration assay using a Transwell demonstrated that there were significantly fewer migrating cells in the lower chamber in the BPHL knockdown NCI-H1299 and A549 cells. Cell cycle analysis by Propidium Iodide (PI) staining and fluorescence activated cell sorter (FACS). We also explored the effect of BPHL knockdown on tumor growth in a mouse model of tumor implantation in nude mice. Results: We found that the knockdown of BPHL gene expression by short hairpin RNA (shRNA) leads to a decrease in proliferation, colony formation, and metastasis and an increase in apoptosis in two lung adenocarcinoma (LUAD) cell lines in vitro. BPHL knockdown induces decreased tumor growth, colony formation, and metastasis; increased apoptosis; and altered cell cycle destruction. BPHL knockdown results in decreased tumor growth in vivo. Moreover, BPHL knockdown A549 cells demonstrated slower growth compared to control cells upon implantation in nude mice, confirming the in vitro findings. Conclusions: In this study, the data indicate that BPHL potentially promotes proliferation, inhibits apoptosis, and increases colony formation and metastasis in lung cancer. Overall, our study suggests that BPHL may be a gene that promotes tumor growth in lung cancer.

LncReader: identification of dual functional long noncoding RNAs using a multi-head self-attention mechanism.

Long noncoding ribonucleic acids (RNAs; LncRNAs) endowed with both protein-coding and noncoding functions are referred to as 'dual functional lncRNAs'. Recently, dual functional lncRNAs have been intensively studied and identified as involved in various fundamental cellular processes. However, apart from time-consuming and cell-type-specific experiments, there is virtually no in silico method for predicting the identity of dual functional lncRNAs. Here, we developed a deep-learning model with a multi-head self-attention mechanism, LncReader, to identify dual functional lncRNAs. Our data demonstrated that LncReader showed multiple advantages compared to various classical machine learning methods using benchmark datasets from our previously reported cncRNAdb project. Moreover, to obtain independent in-house datasets for robust testing, mass spectrometry proteomics combined with RNA-seq and Ribo-seq were applied in four leukaemia cell lines, which further confirmed that LncReader achieved the best performance compared to other tools. Therefore, LncReader provides an accurate and practical tool that enables fast dual functional lncRNA identification.

Functional design and biomechanical evaluation of 3D printing PEEK flexible implant for chest wall reconstruction.

BACKGROUND AND OBJECTIVE: Rigid reconstruction of chest wall defect seriously affects the postoperative respiratory owing to neglecting the functional role of natural costal cartilage. In the study, a 3D printing PEEK flexible implant was developed to restore the deformation capability during breathing motion. MATERIALS AND METHODS: Bionic spring structures in different region of implant were designed by taking into consideration of the anatomical morphology and materials properties of costal cartilage. The biomechanical properties of the rigid and flexible implants under the chest compression were compared through the finite element analysis. Two kinds of chest wall implant samples were fabricated with fused deposition modeling (FDM) technology to evaluate experimentally the mechanical behaviors. Finally, the restoration ability of respiratory function from the flexible implant was investigated in vivo. RESULTS: The flexible implant exhibited the similar stiffness to the natural thorax and satisfied the strength demand in the chest compression. The maximal impact force of flexible implant reached to 536 N. The fatigue failure of complete flexible implant was revealed from the initiation and propagation of interlaminar crack to the fracture in a zigzag manner. Animal experiments validated that the parameters characterizing respiratory could be recovered to the preoperative and normal state. CONCLUSIONS: In the study, the flexible implant provided these advantages for perfect replication of thoracic shape, reliable safety, and great deformation capability to response respiratory movement, which given a superior treatment for chest wall reconstruction.

A deep learning based CT image analytics protocol to identify lung adenocarcinoma category and high-risk tumor area.

We present a protocol which implements deep learning-based identification of the lung adenocarcinoma category with high accuracy and generalizability, and labeling of the high-risk area on Computed Tomography (CT) images. The protocol details the execution of the python project based on the dataset used in the original publication or a custom dataset. Detailed steps include data standardization, data preprocessing, model implementation, results display through heatmaps, and statistical analysis process with Origin software or python codes. For complete details on the use and execution of this protocol, please refer to Chen et al. (2022).

CircRNA PTPRM Promotes Non-Small Cell Lung Cancer Progression by Modulating the miR-139-5p/SETD5 Axis.

Introduction: Circular RNAs (circRNAs) are important regulators in various cancers, especially hepatocellular carcinoma. However, the role of circ RNA PTPRM (circPTPRM) in the development of non-small-cell lung cancer (NSCLC) remains unclear. Methods: We collected 26 clinical specimens (corresponding to 26 normal lung tissues) of lung adenocarcinoma and the expression of mir-139-5p and circPTPRM were first detected. Cell proliferation was detected by EdU method, invasion/migration ability of cells was evaluated by transwell method. And the correlation between circPTPRM and mir-139-5p was detected by luciferase reporter gene and RNA pull-down assay. Finally, we verified our hypothesis with BALB/c nude mice. Results: Through bioinformatics software, we found that circPTPRM was negatively correlated with mir-139-5p, and then we used human adenocarcinoma tissue samples to further verify their relationship and get the same result. EdU method, transwell method, and luciferase assay, RNA pull-down assay were applied, and the results show that the knockdown of circPTPRM inhibit proliferation, migration, and invasion of cells can be reversed by mir-139-5p inhibitor. Next, we used Starbase v2.0 to identify the target site of miR-139-5p and focused on SET domain containing 5 (SETD5). We derive the hypothesis by verifying the relationship between miR-139-5p and SETD5 that circPTPRM may interact with miR-139-5p/SETD5 axis. At last, we evaluated the effects of circPTPRM, SETD5, and miR-139-5p on tumor growth in vivo using BALB/c nude mice to prove the hypothesis. Conclusion: We thus conclude that circPTPRM promotes the progression of NSCLC by regulating the miR-139-5p/SETD5 axis.

High-throughput membrane-anchored proteome screening reveals PIEZO1 as a promising antibody-drug target for human esophageal squamous cell carcinoma.

BACKGROUND: Esophageal carcinoma is one of the most fatal cancers worldwide. In China, over 90% of esophageal cancer patients are diagnosed with esophageal squamous cell carcinoma (ESCC). Currently, the survival and prognosis of ESCC patients are not satisfying because of insufficient early screening and lack of efficacious medication. Accumulating studies have suggested that antibody-drug conjugates (ADC) represent a promising antitumor strategy. METHOD: Here, we carried out a specific membrane proteome screening with ESCC patients' samples using a high-throughput antibody microarray to uncover potential targets for ADC development. Candidates were validated with expression and cytotoxicity evaluation both in vitro and in vivo. RESULTS: Our data have shown that the Piezo-Type Mechanosensitive Ion Channel Component 1 (PIEZO1) is particularly overexpressed in human ESCC tumors and can be efficiently internalized when bound with its monoclonal antibody. Furthermore, the PIEZO1 antibody combined with monomethyl auristatin E (MMAE) can specifically kill PIEZO1 high-expressed ESCC tumor cells by inducing cell cycle arrest and apoptosis. More importantly, the Anti-PIEZO1-MMAE can significantly suppress tumor progression in ESCC xenograft tumor models without any obvious side effects. CONCLUSION: Taken together, our work demonstrates that PIEZO1 is a promising target to develop ADCs for human ESCC treatment, providing a new strategy for ESCC patients' personalized therapy.

Machine vision-assisted identification of the lung adenocarcinoma category and high-risk tumor area based on CT images.

Computed tomography (CT) is a widely used medical imaging technique. It is important to determine the relationship between CT images and pathological examination results of lung adenocarcinoma to better support its diagnosis. In this study, a bilateral-branch network with a knowledge distillation procedure (KDBBN) was developed for the auxiliary diagnosis of lung adenocarcinoma. KDBBN can automatically identify adenocarcinoma categories and detect the lesion area that most likely contributes to the identification of specific types of adenocarcinoma based on lung CT images. In addition, a knowledge distillation process was established for the proposed framework to ensure that the developed models can be applied to different datasets. The results of our comprehensive computational study confirmed that our method provides a reliable basis for adenocarcinoma diagnosis supplementary to the pathological examination. Meanwhile, the high-risk area labeled by KDBBN highly coincides with the related lesion area labeled by doctors in clinical diagnosis.

Olmesartan Attenuates Single-Lung Ventilation Induced Lung Injury via Regulating Pulmonary Microbiota.

Single-lung ventilation (SLV) associated acute lung injury is similar to ischemia reperfusion (IR) injury which is usually occurred during lung surgery. Olmesartan (Olm), a novel angiotensin receptor blocker (ARB), has been reported to ameliorate organ IR injury. Several recent studies have shown that lung microbiota may be involved in pulmonary diseases, but the effect of pulmonary microbiota in SLV-induced lung injury has not been reported. This study aims to determine the mechanism of how Olm attenuates SLV induced lung injury. Our data showed that 7 days Olm treatment before modeling markedly alleviated SLV-induced lung injury by suppressing inflammation and reactive oxygen species. Bronchoalveolar lavage fluid samples from the injured side were collected for 16S rRNA gene-based sequencing analysis and 53 different bacteria at the genus and species levels were identified. Furthermore, the injured lung samples were collected for metabolomics analysis using liquid chromatography-mass spectrometry analyses to explore differential metabolites. The Kyoto Encyclopedia of Genes and Genomes (KEGG) was applied to analyze the correlation between differential metabolites and lung microbiota. A total of 38 pathways were identified according to differential metabolites and 275 relevant pathways were enriched via analyzing the microbial community, 24 pathways were both identified by analyzing either metabolites or microbiota, including pyrimidine metabolism, purine metabolism, aminoacyl-tRNA biosynthesis and ATP-binding cassette transporter. Besides classical blockage of the renin-angiotensin II system, Olm could also alleviate SLV-induced lung injury by rewiring the interaction between pulmonary microbiota and metabolites.

5-methylcytosine RNA methylation regulators affect prognosis and tumor microenvironment in lung adenocarcinoma.

Background: Accumulating evidence has shown that 5-methylcytosinec (m5C) RNA methylation plays an essential role in tumorigenesis. However, the roles of m5C regulators in the prognosis, tumor microenvironment (TME), and immunotherapy responses of lung adenocarcinoma (LUAD) have not been fully analyzed. Methods: Based on 14 m5C RNA regulators, we evaluated the m5C RNA modification patterns in patients with LUAD (n=594) in The Cancer Genome Atlas (TCGA). Unsupervised clustering analysis was performed to confirm distinct m5C modification patterns. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to investigate the biological functions of differentially expressed genes (DEGs) among different m5C RNA modification patterns. An m5C signature (m5Csig) was constructed using least absolute shrinkage and selection operator (LASSO) algorithms. The GSE72094 cohort (n=442) from the Gene Expression Omnibus (GEO) was used to validate m5Csig. A receiver operating characteristic (ROC) model was constructed to evaluate the sensitivity and specificity of m5Csig. Tumor-infiltrating immune cells (TIICs) between the high- and low-risk groups were estimated using the Cell Type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm. Results: We identified 3 m5C RNA modification clusters. Overall survival (OS) differed among the 3 clusters. The m5Csig, including TRDMT1, NSUN1, NSUN4, NSUN7, and ALYREF, was constructed to classify patients with LUAD into high- and low-risk groups. The high-risk group, with more immune cell infiltration, had a significantly poorer OS than that the low-risk group, which was associated with better response to immune checkpoint blockade therapy. Conclusions: The present study revealed that m5C RNA regulators play a significant role in TME regulation in LUAD. The m5Csig can predict the prognosis of patients with LUAD and might provide novel strategies for tumor immunotherapy.

CircSCAP interacts with SF3A3 to inhibit the malignance of non-small cell lung cancer by activating p53 signaling.

BACKGROUND: Circular RNA (circRNA) has been recently identified as a critical regulator during carcinogenesis. However, the biological function and potential underlying mechanisms of circRNAs in lung cancer remain to be further elucidated. METHODS: Here, we first evaluated the differentially expressed circRNAs between tumor and the matched adjacent nontumor tissues (3 pairs) of lung cancer patients via circRNA microarray. The expression of top five dysregulated circRNAs were tested in lung cancer cell lines and the circSCAP with concordant alteration in microarray data and cell lines was selected for further investigation. Then we validated the expression level of circSCAP in tumor and corresponding adjacent tissues (161 pairs) from a lung cancer cohort by RT-PCR analysis followed by correlation and prognosis analysis between circSCAP and clinical characteristics. Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer diagnosis (about 80% in the cohort used in this study). Therefore, we focused the role of circSCAP in NSCLC in the present study. In vitro and in vivo assays were performed to study the biological function of circSCAP in NSCLC. Biotin-labeled RNA pulldown and RNA immunoprecipitation (RIP) assays were carried out to identify the proteins directly interacting with circSCAP. The molecular mechanism of circSCAP-driven tumor suppression was demonstrated by immunoblotting, immunoprecipitation and luciferase reporter assays. In vitro and in vivo rescue experiments were conducted to verify the role of the circSCAP/SF3A3/p53 signaling axis in NSCLC. RESULTS: We screened the expression profiles of human circRNAs in lung cancer tissues and found that hsa_circ_0065214 (termed as circSCAP) was significantly decreased. Kaplan-Meier analysis showed that patients with low level of circSCAP had a significantly poor prognosis. Gain- and loss-of-function experiments suggested that circSCAP played an important role in NSCLC cell proliferation, cell migration and apoptosis. Mechanistically, circSCAP directly binds to the SF3A3 protein, facilitating the reduction of SF3A3 by promoting its ubiquitin-proteasome-mediated degradation, which enhances the expression of MDM4-S to finally activate its downstream p53 signaling. CONCLUSION: These findings illustrate a novel circSCAP/SF3A3/p53 signaling axis involved in suppressing the malignance of NSCLC and provide a promising target for NSCLC prognosis prediction and treatment.

Dielectric property measurements for the rapid differentiation of thoracic lymph nodes using XGBoost in patients with non-small cell lung cancer: a self-control clinical trial.

Background: One of the important criteria for thoracic surgeons in making surgical strategies is whether the thoracic lymph nodes (LNs) are metastatic. Frozen section (FS) is widely used as an intraoperative diagnostic method, which is time-consuming and expensive. The dielectric property, including permittivity and conductivity, varies with different tissues. The extreme gradient boosting (XGBoost) is a powerful classifier and widely used. Thus, this study aims to develop the rapid differentiation method combining dielectric property and XGBoost, and assess its efficacy on the thoracic LNs in patients with non-small cell lung cancer (NSCLC). Methods: This was a single center self-control clinical trial with paraffin pathology section (PPS) results as gold diagnosis. The LNs from the pathologically diagnosed patients with NSCLC were recruited, which were measured by open-ended coaxial probe for the dielectric property within 1-4,000 MHz after removal from the patients and then were sent to perform FS and PPS diagnosis. The XGBoost combining with dielectric property was developed to differentiate malignant LNs from benign LNs. The classified efficacy was determined using the receiver operator characteristic (ROC) curve and area under the curve (AUC). Results: A total of 204 LNs from 67 NSCLC patients were analyzed. The mean values of the two parameters differed significantly (P<0.001) between benign and malignant LNs. The AUC for permittivity and conductivity were 0.850 [95% confidence interval (CI): 0.786 to 0.915; P<0.001] and 0.887 (95% CI: 0.828 to 0.946; P<0.001), respectively. The AUC was 0.893 (95% CI: 0.834 to 0.951; P<0.001) when the two parameters were combined. After the application of the XGBoost, the AUC was 0.968 (95% CI: 0.918 to 1.000; P<0.001), and the accuracy was 87.80%. Its sensitivity was 58.33% and the specificity was 100%. When the Synthetic Minority Oversampling Technique (SMOTE) algorithm was used, the AUC was 0.954 (95% CI: 0.883 to 1.000; P<0.001) and the accuracy was 92.68%. Its sensitivity was 83.33% and the specificity was 96.55%. Conclusions: This method might be useful for thoracic surgeons during surgery, for its relatively high efficacy in rapid differentiation of LNs for patients with NSCLC.

RAD6 Positively Affects Tumorigenesis of Esophageal Squamous Cell Carcinoma by Regulating Histone Ubiquitination of CCNB1.

Objective Esophageal carcinoma (ESCA) is deadly cancer worldwide with unknown etiology. This study aimed to investigate the impact and mechanism of RAD6 on the development of Esophageal squamous cell carcinoma (ESCC).Expressions of RAD6A and RAD6B in ESCA were investigated from TCGA dataset and their expressions in tissue sample of ESCA patients and cells were determined. Functional experiments were conducted to explore the impact of RAD6A and RAD6B on malignant characteristics of several kinds of ESCC cells. Animal experiment was established and injected with RAD6A and RAD6B shRNA to evaluate the effect on tumor growth.RAD6A and RAD6B were up-regulated in ESCC cells and tissues. Overexpressed RAD6A and RAD6B similarly increased ESCC cell proliferation, invasion and migration and silencing of RAD6 exerted opposite effects. Knockdown of RAD6A suppressed tumor growth and decreased the level of H2B, as data demonstrated positive correlation between RAD6A and CCNB1 in ESCC tissues.Collectively, this study elucidates that RAD6 is up-regulated in ESCC and promotes the progression of ESCC through up-regulation of CCNB1 to enhance H2B ubiquitination. These evidence provide a novel insight into the pathogenesis of ESCC and might contribute to the development of targeted therapy.

Integrative pan cancer analysis reveals the importance of CFTR in lung adenocarcinoma prognosis.

Cystic fibrosis (CF) and cystic fibrosis transmembrane conductance regulator (CFTR) mutations have been shown to be associated with the risk of a variety of cancers. However, the clinical significance of aberrant CFTR gene expression in human tumors remains unknown. The expression profiles and prognostic landscapes of CFTR in human cancers were identified from the PubMed, OVID, CNKI, TCGA, ONCOMINE, PrognoScan, and GEPIA databases. Over 11, 000 cancer samples from the literature, GEPIA database, and PrognoScan database were included in this study. In general, CFTR has various expression and prognostic profiles in cancers, but the results from cross-database and meta-analyses revealed that CFTR is a robust biomarker for LUAD prognosis. Collectively, this study suggests that CFTR is an important prognostic biomarker for LUAD survival, implying that it could be used as a prognostic biomarker and therapeutic target for LUAD.

Trends, Symptoms, and Outcomes of Resectable Giant Mediastinal Tumors.

Describing the changes in surgical procedures and factors affecting the surgical outcome of patients who have undergone complete resection of giant mediastinal tumors (GMTs, diameter ≥ 10 centimeters) could improve preoperative decision-making and prognostic evaluations. We accessed data from three sources, which are case reports on surgical treatment of GMTs from PubMed, Web of Science, and EMBASE until June 1, 2019; patients with resected GMT from the Surveillance, Epidemiology, and End Results (SEER) database; and retrospective review of medical records in our institution from 2000 to 2019. The worldwide distribution, clinicopathological characteristics, symptom profile, prognosis of patients with GMT resection, and nomogram for surgical outcome prediction are reported. A total of 242 rare GMT cases from four continents (Asia, North America, South America, and Europe) were included. The median age of the patients was 40 (IQR: 27, range: 13-83) years, and the male-to-female ratio was 1.57:1. Dyspnea, shortness of breath, cough, and chest pain or discomfort were the major symptoms at presentation. The prognosis of benign and low-grade malignant GMTs was superior to that of high-grade malignant GMTs. Tumor malignancy played the most critical role in predicting postoperative survival, followed by longest tumor diameter and a posterior mediastinum location. The findings of this study suggest that the number of successful GMT surgeries has increased over the last decade and describe clinical features of GMTs. Physicians should prioritize tumor malignancy as a leading factor in predicting outcome rather than tumor size.