eccDB: a comprehensive repository for eccDNA-mediated chromatin contacts in multi-species.

SUMMARY: We developed the eccDB database to integrate available resources for extrachromosomal circular DNA (eccDNA) data. eccDB is a comprehensive repository for storing, browsing, searching, and analyzing eccDNAs from multispecies. The database provides regulatory and epigenetic information on eccDNAs, with a focus on analyzing intrachromosomal and interchromosomal interactions to predict their transcriptional regulatory functions. Moreover, eccDB identifies eccDNAs from unknown DNA sequences and analyzes the functional and evolutionary relationships of eccDNAs among different species. Overall, eccDB offers web-based analytical tools and a comprehensive resource for biologists and clinicians to decipher the molecular regulatory mechanisms of eccDNAs. AVAILABILITY AND IMPLEMENTATION: eccDB is freely available at http://www.xiejjlab.bio/eccDB.

TRlnc: a comprehensive database for human transcriptional regulatory information of lncRNAs.

Long noncoding RNAs (lncRNAs) have been proven to play important roles in transcriptional processes and biological functions. With the increasing study of human diseases and biological processes, information in human H3K27ac ChIP-seq, ATAC-seq and DNase-seq datasets is accumulating rapidly, resulting in an urgent need to collect and process data to identify transcriptional regulatory regions of lncRNAs. We therefore developed a comprehensive database for human regulatory information of lncRNAs (TRlnc, http://bio.licpathway.net/TRlnc), which aimed to collect available resources of transcriptional regulatory regions of lncRNAs and to annotate and illustrate their potential roles in the regulation of lncRNAs in a cell type-specific manner. The current version of TRlnc contains 8 683 028 typical enhancers/super-enhancers and 32 348 244 chromatin accessibility regions associated with 91 906 human lncRNAs. These regions are identified from over 900 human H3K27ac ChIP-seq, ATAC-seq and DNase-seq samples. Furthermore, TRlnc provides the detailed genetic and epigenetic annotation information within transcriptional regulatory regions (promoter, enhancer/super-enhancer and chromatin accessibility regions) of lncRNAs, including common SNPs, risk SNPs, eQTLs, linkage disequilibrium SNPs, transcription factors, methylation sites, histone modifications and 3D chromatin interactions. It is anticipated that the use of TRlnc will help users to gain in-depth and useful insights into the transcriptional regulatory mechanisms of lncRNAs.

Prognostic Value of SSTR-derived Volumetric Parameters from a Hybrid Standardized Uptake Value Thresholding Method in Patients with 68Ga-DOTATATE-avid Stage IV Neuroendocrine Neoplasms: A preliminary study.

INTRODUCTION: The ability of PET/CT imaging to delineate neuroendocrine neoplasms (NENs) and predict prognosis in affected patients is often compromised by substantial uptake heterogeneity. We hereby proposed a hybrid standardized uptake value (SUV) thresholding algorithm to extract volumetric parameters from somatostatin receptor (SSTR) PET/CT imaging, and investigate their prognostic performance in patients with 68Ga-DOTATATE-avid stage IV NENs. METHODS: For 38 retrospectively enrolled patients, we used either fixed SUV thresholding of normal liver parenchyma (method A), 41% of the SUVmax for each lesion (method B), or a hybrid method (method A for liver metastases; fixed SUV threshold of normal bone for bone metastases; method B for primary tumors and other metastases) to quantify the whole-body SSTR-expressing tumor volume (SRETVwb) and total lesion SSTR expression (TLSREwb). Patient survival was also recorded and analyzed. RESULTS: PET/CT images revealed heterogeneous uptake of 68Ga-DOTATATE at primary and metastatic sites. Progression-free (PFS) and overall survival (OS) were negatively correlated with the extent of liver or bone metastases (P < 0.05), but not significantly correlated with tumor grade or 18F-FDG PET/CT positivity. By the hybrid method, PFS was significantly shorter in patients with high SRETVwb, and OS was significantly shorter in those with high SRETVwb and TLSREwb (P < 0.05). However, when derived from method A or method B, neither SRETVwb nor TLSREwb could predict patient outcomes. CONCLUSION: Compared with other methods used in 68Ga-DOTATATE-avid stage IV NENs, our hybrid SUV thresholding method demonstrated robustness, with greater precision, reliability, and prognostic power.

N6-methyladenosine reader YTHDC2 and eraser FTO may determine hepatocellular carcinoma prognoses after transarterial chemoembolization.

Transarterial chemoembolization (TACE) has significantly improved overall survival (OS) of unresectable hepatocellular carcinoma (HCC) patients. Unfortunately, a portion of patients show no therapeutic responses to TACE. N6-methyladenosine (m6A) as well as its epigenetic writers, erasers, and readers play a crucial role in HCC development. However, it is still largely unclear how functional small nucleotide polymorphisms (SNPs) in m6A-regulating genes contribute to prognosis of TACE-treated HCC patients. In this study, potential functional SNPs were systematically evaluated to identify their roles in the prognosis of HCC patients after TACE in a Chinese Han population. Employing multiple databases, we successfully annotated 55 candidate SNPs. After genotyping these SNPs in our TACE cohort, we identified three genetic variants in YTHDC2 (rs6594732, rs10071816, and rs2303718) and one SNP in FTO (rs7202116) having statistically significant associations with the OS of HCC patients treated with TACE. For example, multivariate Cox proportional hazards model indicated that the rs7202116 GG genotype carriers had markedly shorter OS and an 87% increased death risk compared with the AA carriers after TACE therapy (P = 0.002). When investigating functional relevance of these SNPs, we observed an allelic regulation of rs7202116 on FTO expression in HCC tissue samples, with higher tumor suppressor FTO expression among the A allele carriers. Our findings reported the first evidence supporting the prognostic value of m6A reader YTHDC2 and m6A eraser FTO SNPs in TACE-treated HCC patients. Importantly, our data implicated that m6A-regulating genes may be targets to improve therapeutic strategy for unresectable HCC patients.

Laparoscopic Kasai portoenterostomy for cystic biliary atresia: midterm follow-up results of 35 patients.

PURPOSE: To investigate the clinical characteristics of cystic biliary atresia (CBA) and evaluate the midterm follow-up outcomes after laparoscopic treatment. METHODS: We analyzed and compared data retrospectively on CBA patients (group A) and nonsyndromic type III biliary atresia (BA) patients (group B), who underwent laparoscopic Kasai portoenterostomy (LKPE) during the same period. RESULTS: There were no significant differences in operative time, conversion rate, or the incidence of any postoperative complications between groups A and B (P > 0.05). The mean age at surgery (P < 0.01), rates of clearance of jaundice (CJ), cholangitis (P < 0.05), and 5-year survival with a native liver (SNL) were significantly lower in group A than in group B. Among the 35 patients with CBA, the CJ and 5-year SNL rates were significantly better in those with type I (n = 27) than in those with type IIId (n = 8) (P < 0.05). CONCLUSIONS: LKPE is a feasible and safe procedure for CBA. The 5-year SNL after LKPE was better in patients with CBA than in those with nonsyndromic type III BA. The 5-year SNL after LKPE for type I CBA was better than that for type IIId CBA.

Applying protein-based amide proton transfer MR imaging to distinguish solitary brain metastases from glioblastoma.

OBJECTIVES: To determine the utility of amide proton transfer-weighted (APTw) MR imaging in distinguishing solitary brain metastases (SBMs) from glioblastomas (GBMs). METHODS: Forty-five patients with SBMs and 43 patients with GBMs underwent conventional and APT-weighted sequences before clinical intervention. The APTw parameters and relative APTw (rAPTw) parameters in the tumour core and the peritumoral brain zone (PBZ) were obtained and compared between SBMs and GBMs. The receiver-operating characteristic (ROC) curve was used to assess the best parameter for distinguishing between the two groups. RESULTS: The APTwmax, APTwmin, APTwmean, rAPTwmax, rAPTwmin or rAPTwmean values in the tumour core were not significantly different between the SBM and GBM groups (P = 0.141, 0.361, 0.221, 0.305, 0.578 and 0.448, respectively). However, the APTwmax, APTwmin, APTwmean, rAPTwmax, rAPTwmin or rAPTwmean values in the PBZ were significantly lower in the SBM group than in the GBM group (P < 0.001). The APTwmin values had the highest area under the ROC curve 0.905 and accuracy 85.2% in discriminating between the two neoplasms. CONCLUSION: As a noninvasive imaging method, APT-weighted MR imaging can be used to distinguish SBMs from GBMs. KEY POINTS: • APTw values in the tumour core were not different between SBMs and GBMs. • APTw values in peritumoral brain zone were lower in SBMs than in GBMs. • The APTw min was the best parameter to distinguish SBMs from GBMs.

The Development of Diabetic Retinopathy in Goto-Kakizaki Rat and the Expression of Angiogenesis-Related Signals.

The Goto-Kakizaki (GK) rat is a genetic model of type 2 diabetes. Diabetic retinopathy (DR) is a common complication of diabetes. In this study, we observed the development of DR in GK rats and the expression of some angiogenesis-related signals. GK rats were housed for 5, 6 and 7 months. Results of retinal vessels stained by cluster of differentiation 31 (CD31) showed that the number of retinal vessels was increased in GK rats at both 6 and 7 months. Retinal histological observation also evidenced such increase. Retinal mRNA expression of hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), VEGFB and its receptors (VEGFR1/2), basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF) A/B was increased in GK rats at both 6 and 7 months. Retinal mRNA expressions of matrix metalloproteinase (MMP) 2/9 and insulin-like growth factor 1 (IGF-1) were increased at 7 months. Retinal mRNA expression of pigment epithelium-derived factor (PEDF) was increased in GK rats at 6 months. Serum contents of VEGF, bFGF, PDGFA, MMP2/9, IGF-1, PEDF were increased in GK rats at both 6 and 7 months, while PDGFB was increased at 7 months. In summary, our results indicate that retinal angiogenesis occurred in GK rats at 6 and 7 months, and the expressions of some angiogenesis related factors were increased during the development of DR in GK rats.

Hepatic perivascular epithelioid cell tumor resembling hepatic adenoma and hepatocellular carcinoma on preoperative imaging: a case report.

Perivascular epithelioid cell tumor (PEComa), an uncommon mesenchymal neoplasm, arises from specialized perivascular epithelioid cells exhibiting distinct features of smooth muscle and melanocytic differentiation with unpredictable behavior. PEComa tends to occur more commonly in the uterus and kidneys; its occurrence in the liver is exceedingly rare. We presented a case of a 29-year-old woman with hepatic PEComa and evaluated the tumor with MRI, integrated 18F-fluorodeoxyglucose (FDG), and 68Ga-fibroblast activation protein inhibitor (FAPI) PET/CT scans at presentation. The patient had a history of intermittent utilization of oral contraceptive drugs for several years. An abdominal ultrasound in a physical examination from an outside institution revealed a mass in the liver. A contrast-enhanced abdominal MRI revealed restricted diffusion on diffusion-weighted imaging (DWI) and rapid contrast enhancement and washout patterns in the hepatic lesion, suggesting hepatic adenoma (HA) or hepatocellular carcinoma (HCC). Further assessment was carried out using 18F-FDG and 68Ga-FAPI PET/CT scans. The hepatic lesion was non-FDG avid, whereas increased tracer uptake was observed on the 68Ga-FAPI PET/CT. Subsequently, laparoscopic partial resection of liver segment V was performed. Immunohistochemical analyses demonstrated positive staining for HMB45, Melan-A, and SMA while showing negative results for AFP, glypican-3, hepatocyte, and arginase-1. The results were indicative of a hepatic PEComa diagnosis based on these findings. We also review the current literature on the clinical characteristics, pathological features, and challenges in the diagnosis of hepatic PEComa.

What are the demands of telegeriatrics medical services for elderly patients during the COVID-19 pandemic.

Purpose: Elderly patients are associated with a higher risk of nosocomial cross infection during the COVID-19 pandemic. Providing medical services and primary care for elderly patients is a worldwide challenge. A new telegeriatrics system was established to provide medical services and primary care for elderly patients treated by family physicians. This study aimed to describe the operation mechanism of the new system and investigate the demands of telegeriatrics medical services for elderly patients treated by family physicians during the COVID-19 pandemic. Methods: A total of 1,353 elderly patients (aged≥60) treated by family physicians were enrolled. The proportion of the top 10 diseases of elderly patients applying the new system was analyzed. Differences in main diseases between elderly patients applying telegeriatrics medical services and outpatients in hospitals were compared. Differences between the new telegeriatrics system in our study and telemedicine systems of other studies in other countries were analyzed. Results: Constituent ratios of chronic kidney disease, type 2 diabetes mellitus, and coronary heart disease have the highest rate in elderly patients applying the new telegeriatrics system. Digestive diseases, cardiovascular diseases, and neurology diseases were the top three diseases of elderly outpatients. Conclusion: This is the first time that a new telegeriatrics system has been applied to provide medical services for elderly patients treated by family physicians during the COVID-19 pandemic. Chronic kidney disease, Type 2 diabetes mellitus, and coronary heart disease were found to be the top three diseases of elderly patients applying telegeriatrics medical services during the COVID-19 pandemic, which were different from the outpatients in general hospitals. The new telegeriatrics system guarantees elderly patients get equal rights to medical services. Results will provide a basis for the government health administrative department to formulate new telegeriatrics policies for elderly patients.

Investigating the demands for mobile internet-based home nursing services for the elderly.

The great value of home nursing services in the treatment of ailments in elderly patients has attracted increasing attention. This study describes a new mobile internet-based home nursing service system and investigates the reasons for its use among elderly patients. 520 cases of mobile internet-based home nursing services were investigated. The proportion of major reasons to use mobile internet-based home nursing services among the elderly was analyzed and the satisfaction rate was investigated. The constituent ratios of nursing care for pressure ulcers, peripherally inserted central catheter (PICC), subcutaneous injection, general stoma care, psychological care, and intramuscular injection were 61.35%, 28.85%, 6.15%, 1.92%, 1.35%, and 0.38%, respectively. The satisfaction rate with mobile internet-based home nursing services among elderly patients was 100%. Considering the demand for home nursing services for elderly patients, this is the first time that a new mobile internet-based home nursing service has been applied to provide home nursing services to elderly patients and meet their home nursing service needs. Treatment for pressure ulcers, PICC, subcutaneous injection, general stoma care, psychological care, and intramuscular injection were found to be the main reasons to use mobile internet-based home nursing services among the elderly. The new mobile internet-based home nursing service system provides convenient home nursing services to elderly patients and ensures that they get equal rights in home nursing. The results provide basis for healthcare policy makers to formulate new home nursing policies for elderly patients.

Time point-independent tumor positivity of 68Ga-PSMA-PET/CT pre- and post-biopsy in high-risk prostate cancer.

OBJECTIVE: Prostate-specific membrane antigen (PSMA)-PET/CT imaging has gained increasing clinical importance for the detection and staging of high-risk primary prostate cancer (PCa). However, it is unclear whether the routine practice of prostate biopsy obscures the image finding of PSMA-PET/CT. This study aimed to compare the tumor positivity rate of PSMA-PET/CT performed pre- (PSMA-PET/CTpre) and post-biopsy (PSMA-PET/CTpost) in high-risk PCa patients. PATIENTS AND METHODS: We matched 58 PSMA-PET/CTpost with 58 PSMA-PET/CTpre studies for primary detection of high-risk PCa according to clinical characteristics. Three subgroups of PSMA-PET/CTpost were defined by the intervals after biopsy (≤ 1 week, 1 ~ 2 weeks, and 2 ~ 5 weeks). Tumor positivity rates were determined, and SUVmax of primary tumors were compared separately for the two main groups and the related subgroups. Malignant prostate tissues from 20 of these patients were examined by immunohistochemical analysis of PSMA. In addition, the values of PSMA-PET/CTpre and PSMA-PET/CTpost in assessing seminal vesicle invasion (SVI) were evaluated in patients who underwent radical prostatectomy. RESULTS: All the primary tumors were positive on PSMA-PET/CTpost and PSMA-PET/CTpre imaging, resulting in a patient-based positivity rates of 100% (58/58) in both groups. All examined IHC results (20/20) confirmed the high-level expression of PSMA. SUVmax of primary tumors did not differ between the two main groups (16.1, IQR 9.8-26.6 vs. 16.5, IQR 11.0-26.7, p > 0.05). Subgroup analysis of PSMA-PET/CTpost (≤ 1 week, 1 ~ 2 weeks, and 2 ~ 5 weeks) also showed no significant difference in tumor SUVmax (15.8, IQR 9.5-22.2; 17.8, IQR 9.8-29.2; and 15.4, IQR 10.1-30.3. p > 0.05). PSMA-PET/CTpost and PSMA-PET/CTpre exhibited similar value in SVI detection as well. CONCLUSIONS: The tumor positivity rate was consistently high for PSMA-PET/CT pre- and post-biopsy. A prior biopsy does not seem to affect the tumor positivity rate of PSMA-PET/CT in high-risk PCa.

Primary Inferior Vena Cava Leiomyosarcoma With Hepatic Metastases on FDG PET/CT.

ABSTRACT: Leiomyosarcomas originating from the inferior vena cava are very rare malignant tumors with an extremely poor prognosis. We report FDG PET/CT findings of pathology-proven hepatic metastases from leiomyosarcoma originating from the inferior vena cava in a young woman whose initial presentation was worsening abdominal and chest pain.

A Novel Approach Using FDG-PET/CT-Based Radiomics to Assess Tumor Immune Phenotypes in Patients With Non-Small Cell Lung Cancer.

PURPOSE: Tumor microenvironment immune types (TMITs) are closely related to the efficacy of immunotherapy. We aimed to assess the predictive ability of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)-based radiomics of TMITs in treatment-naive patients with non-small cell lung cancer (NSCLC). METHODS: A retrospective analysis was performed in 103 patients with NSCLC who underwent 18F-FDG PET/CT scans. The patients were randomly assigned into a training set (n = 71) and a validation set (n = 32). Tumor specimens were analyzed by immunohistochemistry for the expression of programmed death-ligand 1 (PD-L1), programmed death-1 (PD-1), and CD8+ tumor-infiltrating lymphocytes (TILs) and categorized into four TMITs according to their expression of PD-L1 and CD8+ TILs. LIFEx package was used to extract radiomic features. The optimal features were selected using the least absolute shrinkage and selection operator (LASSO) algorithm, and a radiomics signature score (rad-score) was developed. We constructed a combined model based on the clinical variables and radiomics signature and compared the predictive performance of models using receiver operating characteristic (ROC) curves. RESULTS: Four radiomic features (GLRLM_LRHGE, GLZLM_SZE, SUVmax, NGLDM_Contrast) were selected to build the rad-score. The rad-score showed a significant ability to discriminate between TMITs in both sets (p < 0.001, p < 0.019), with an area under the ROC curve (AUC) of 0.800 [95% CI (0.688-0.885)] in the training set and that of 0.794 [95% CI (0.615-0.916)] in the validation set, while the AUC values of clinical variables were 0.738 and 0.699, respectively. When clinical variables and radiomics signature were combined, the complex model showed better performance in predicting TMIT-I tumors, with the AUC values increased to 0.838 [95% CI (0.731-0.914)] in the training set and 0.811 [95% CI (0.634-0.927)] in the validation set. CONCLUSION: The FDG-PET/CT-based radiomic features showed good performance in predicting TMIT-I tumors in NSCLC, providing a promising approach for the choice of immunotherapy in a clinical setting.

Implications of protein ubiquitination modulated by lncRNAs in gastrointestinal cancers.

Long non-coding RNAs (lncRNAs) are a class of RNA transcripts longer than 200 nucleotides and mostly cannot be translated into proteins. Next-generation transcriptome sequencing of various cell types has enabled the annotation of tens of thousands of lncRNAs in human genome. Varying levels of evidence supports the implications of lncRNAs in the onset and progression of cancers. Ubiquitin is an evolutionarily conserved protein and could post-translationally mark a number of proteins. The most important proteolytic role of ubiquitination is degradation of substrate proteins by the 26S proteasome. Compiling evidences demonstrated that lncRNAs are involved in the accurate execution of protein stability programs via the ubiquitin-proteasome system. In the current review, we systematically summarize the detailed mechanisms how lncRNAs modulate ubiquitination of target proteins, regulate cancerous signaling pathways and control tumorigenesis of gastrointestinal cancers. Although there are still considerable studies on unraveling the complicated interactions between lncRNAs and proteins, we believe that lncRNAs are promising but challenging molecules which may strongly facilitate precision cancer therapeutics in the future.

Marine Biofilms with Significant Corrosion Inhibition Performance by Secreting Extracellular Polymeric Substances.

The development of environmentally friendly and sustainable corrosion protection technologies is a longstanding yet difficult problem, especially for the marine environment. The utilization of living biofilms isolated from local environments is an effective strategy for infrastructure protection. In this study, three aerobic marine bacteria, Tenacibaculum mesophilum D-6, Tenacibaculum litoreum W-4, and Bacillus sp. Y-6, with strong biofilm-forming abilities were isolated and evaluated for the corrosion protection of X80 carbon steel. The corrosion inhibitory effect of the bacteria was found to be closely related to their biofilm-forming abilities. This conclusion was corroborated by biofilm characterization, electrochemical tests, weight loss analysis, and corrosion product analysis. Moreover, secreted extracellular polymeric substances were identified to play significant roles in corrosion inhibition. Herein, we proposed a novel, eco-friendly, and cost-effective method for corrosion protection of carbon steels in the marine environment, providing guiding principles for identifying corrosion inhibitory bacteria from the local marine environment.

Correlation Between Dual-Time-Point FDG PET and Tumor Microenvironment Immune Types in Non-Small Cell Lung Cancer.

PURPOSE: Dual-time-point 18F-fluorodeoxyglucose positron emission tomography (DTP 18F-FDG PET), which reflects the dynamics of tumor glucose metabolism, may also provide a novel approach to the characterization of both cancer cells and immune cells within the tumor immune microenvironment (TIME). We investigated the correlations between the metabolic parameters (MPs) of DTP 18F-FDG PET images and the tumor microenvironment immune types (TMITs) in patients with non-small cell lung cancer (NSCLC). METHODS: A retrospective analysis was performed in 91 patients with NSCLC who underwent preoperative DTP 18F-FDG PET/CT scans. MPs in the early scan (eSUVmax, eSUVmean, eMTV, eTLG) and delayed scan (dSUVmax, dSUVmean, dMTV, dTLG) were calculated, respectively. The change in MPs (ΔSUVmax, ΔSUVmean, ΔMTV, ΔTLG) between the two time points were calculated. Tumor specimens were analyzed by immunohistochemistry for PD-1/PD-L1 expression and CD8+ tumor-infiltrating lymphocytes (TILs). TIME was classified into four immune types (TMIT I ~ IV) according to the expression of PD-L1 and CD8+ TILs. Correlations between MPs with TMITs and the immune-related biomarkers were analyzed. A composite metabolic signature (Meta-Sig) and a combined model of Meta-Sig and clinical factors were constructed to predict patients with TMIT I tumors. RESULTS: eSUVmax, eSUVmean, dSUVmax, dSUVmean, ΔSUVmax, ΔSUVmean, and ΔTLG were significantly higher in PD-L1 positive patients (p = 0.0007, 0.0006, < 0.0001, < 0.0001, 0.0002, 0.0002, 0.0247, respectively), and in TMIT-I tumors (p = 0.0001, < 0.0001, < 0.0001, < 0.0001, 0.0009, 0.0009, 0.0144, respectively). Compared to stand-alone MP, the Meta-Sig and combined model displayed better performance for assessing TMIT-I tumors (Meta-sig: AUC = 0.818, sensitivity = 86.36%, specificity = 73.91%; Model: AUC = 0.869, sensitivity = 77.27%, specificity = 82.61%). CONCLUSION: High glucose metabolism on DTP 18F-FDG PET correlated with the TMIT-I tumors, and the Meta-Sig and combined model based on clinical and metabolic information could improve the performance of identifying the patients who may respond to immunotherapy.

Serum CYR61 as a potential biomarker for the diagnosis of esophagogastric junction tumor.

BACKGROUND: Esophagogastric junction tumor (EGJ) is a rare but fatal disease with a rapid rising incidence worldwide in the late 20 years, and it lacks a convenient and safe method for diagnosis. The present study aimed to evaluate the potential of serum CYR61 as a biomarker for the diagnosis of EGJ tumor. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to estimate CYR61 levels in sera of 152 EGJ tumor patients and 137 normal controls. Receiver operating characteristics (ROC) was carried out to evaluate the diagnostic accuracy. The Mann-Whitney's U test was used to compare the difference of serum levels of CYR61 between groups. And chi-square tests were employed to estimate the correlation of the positive rate of serum CYR61 between/among subgroups. RESULTS: Serum CYR61 levels were statistically lower in EGJ tumor and early-stage EGJ tumor patients than those in normal controls (P<0.0001). The sensitivity, specificity and the area under the curve (AUC) of this biomarker in EGJ tumor were 88.2%, 43.8% and 0.691, respectively, and those for early stage of EGJ tumor were 80.0%, 66.4% and 0.722, respectively. Analyses showed that there was no correlation between the clinical data and the levels of CYR61 (P>0.05). CONCLUSION: The present study showed that CYR61 might be a potential biomarker to assist the diagnosis of EGJ tumor.

CATA: a comprehensive chromatin accessibility database for cancer.

Accessible chromatin refers to the active regions of a chromosome that are bound by many transcription factors (TFs). Changes in chromatin accessibility play a critical role in tumorigenesis. With the emergence of novel methods like Assay for Transposase-accessible Chromatin Sequencing, a sequencing method that maps chromatin-accessible regions (CARs) and enables the computational analysis of TF binding at chromatin-accessible sites, the regulatory landscape in cancer can be dissected. Herein, we developed a comprehensive cancer chromatin accessibility database named CATA, which aims to provide available resources of cancer CARs and to annotate their potential roles in the regulation of genes in a cancer type-specific manner. In this version, CATA stores 2 991 163 CARs from 23 cancer types, binding information of 1398 TFs within the CARs, and provides multiple annotations about these regions, including common single nucleotide polymorphisms (SNPs), risk SNPs, copy number variation, somatic mutations, motif changes, expression quantitative trait loci, methylation and CRISPR/Cas9 target loci. Moreover, CATA supports cancer survival analysis of the CAR-associated genes and provides detailed clinical information of the tumor samples. Database URL: CATA is available at http://www.xiejjlab.bio/cata/.

Prostate-specific membrane antigen expression in hepatocellular carcinoma, cholangiocarcinoma, and liver cirrhosis.

BACKGROUND: Primary liver cancer includes three subtypes: Hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (CCA), and combined hepatocellular carcinoma. Patients with primary liver cancer experienced poor prognosis and high mortality, so early detection of liver cancer and improved management of metastases are both key strategies to reduce the death toll from liver cancer. Prostate-specific membrane antigen (PSMA) expression in the tumor-associated neovasculature of nonprostate malignancies including liver cancer has been reported recently, but conclusive evidence of PSMA expression based on the pathological type of liver cancer remains limited. AIM: To study the expression of PSMA in HCC, CCA, and liver cirrhosis. METHODS: A total of 446 formalin-fixed paraffin-embedded (FFPE) liver tumor and liver cirrhosis tissue samples were obtained retrospectively from the Pathology Department of Tongji Hospital. Immunohistochemistry was used to detect PSMA expression in these 446 FFPE liver biopsy specimens (213 HCC, 203 CCA, and 30 liver cirrhosis). The tumor compartment and the associated neovascular endothelium were separately analyzed. PSMA expression was examined by two certified pathologists, and the final results were presented in a 4-point scoring system (0-3 points). Correlation between PSMA expression and clinicopathological information was also assessed. RESULTS: PSMA was expressed primarily in the neovascular endothelium associated with tumors. The positive rate of PSMA staining in HCC was significantly higher than that in CCA (86.8% vs 79.3%; P = 0.001) but was only 6.6% in liver cirrhosis (P = 0.000). HCC cases had more 3-score PSMA staining than CCA had (89/213, 41.8% vs 35/203, 17.2%; P = 0.001). PSMA expression correlated positively with the stage and grade of HCC and CCA. In both liver cancer subtypes, there were more PSMA+ cases in stages III-V diseases than in stages I and II. High staining intensity of PSMA was more frequently observed in liver cancers at high grade and advanced stage. There was no significant association of PSMA expression with sex, age, region, α-fetoprotein, hepatitis B surface antigen, or tumor size in both tumor subtypes. CONCLUSION: Neovascular PSMA may be a promising marker to differentiate HCC from liver cirrhosis and a prognostic marker for anti-tumor angiogenesis therapy for HCC.

Diagnostic evaluation of HER-2 as a molecular target: an assessment of accuracy and reproducibility of laboratory testing in large, prospective, randomized clinical trials.

PURPOSE: To critically assess the accuracy and reproducibility of human epidermal growth factor receptor type 2 (HER-2) testing in outside/local community-based hospitals versus two centralized reference laboratories and its effect on selection of women for trastuzumab (Herceptin)-based clinical trials. EXPERIMENTAL DESIGN: Breast cancer specimens from 2,600 women were prospectively evaluated by fluorescence in situ hybridization (FISH) for entry into Breast Cancer International Research Group (BCIRG) clinical trials for HER-2-directed therapies. RESULTS: HER-2 gene amplification by FISH was observed in 657 of the 2,502 (26%) breast cancers successfully analyzed. Among 2,243 breast cancers with central laboratory immunohistochemistry (10H8-IHC) analysis, 504 (22.54%) showed overexpression (2+ or 3+). Outside/local laboratories assessed HER-2 status by immunohistochemistry in 1,536 of these cases and by FISH in 131 cases. Overall, the HER-2 alteration status determined by outside/local immunohistochemistry showed a 79% agreement rate [kappa statistic, 0.56; 95% confidence interval (95% CI), 0.52-0.60], with FISH done by the central laboratories. The agreement rate comparing BCIRG central laboratory 10H8-IHC and outside/local laboratory immunohistochemistry was 77.5% (kappa statistic, 0.51; 95% CI, 0.46-0.55). Finally, HER-2 status, determined by unspecified FISH assay methods at outside/local laboratories, showed a 92% agreement rate (kappa statistic, 0.83; 95% CI, 0.73-0.93), with FISH done at the BCIRG central laboratories. CONCLUSIONS: Compared with the HER-2 status determined at centralized BCIRG reference laboratories, these results indicate superiority of FISH to accurately and reproducibly assess tumors for the HER-2 alteration at outside/local laboratories for entry to clinical trials.