Hub genes and their key effects on prognosis of Burkitt lymphoma.

BACKGROUND: Burkitt lymphoma (BL) is an exceptionally aggressive malignant neoplasm that arises from either the germinal center or post-germinal center B cells. Patients with BL often present with rapid tumor growth and require high-intensity multi-drug therapy combined with adequate intrathecal chemotherapy prophylaxis, however, a standard treatment program for BL has not yet been established. It is important to identify biomarkers for predicting the prognosis of BLs and discriminating patients who might benefit from the therapy. Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets. AIM: To identify hub genes and perform gene ontology (GO) and survival analysis in BL. METHODS: Gene expression profiles and clinical traits of BL patients were collected from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA) was applied to construct gene co-expression modules, and the cytoHubba tool was used to find the hub genes. Then, the hub genes were analyzed using GO and Kyoto Encyclopedia of Genes and Genomes analysis. Additionally, a Protein-Protein Interaction network and a Genetic Interaction network were constructed. Prognostic candidate genes were identified through overall survival analysis. Finally, a nomogram was established to assess the predictive value of hub genes, and drug-gene interactions were also constructed. RESULTS: In this study, we obtained 8 modules through WGCNA analysis, and there was a significant correlation between the yellow module and age. Then we identified 10 hub genes (SRC, TLR4, CD40, STAT3, SELL, CXCL10, IL2RA, IL10RA, CCR7 and FCGR2B) by cytoHubba tool. Within these hubs, two genes were found to be associated with OS (CXCL10, P = 0.029 and IL2RA, P = 0.0066) by survival analysis. Additionally, we combined these two hub genes and age to build a nomogram. Moreover, the drugs related to IL2RA and CXCL10 might have a potential therapeutic role in relapsed and refractory BL. CONCLUSION: From WGCNA and survival analysis, we identified CXCL10 and IL2RA that might be prognostic markers for BL.

Predicting MYCN amplification in paediatric neuroblastoma: development and validation of a 18F-FDG PET/CT-based radiomics signature.

OBJECTIVES: To develop and validate an 18F-FDG PET/CT-based clinical-radiological-radiomics nomogram and evaluate its value in the diagnosis of MYCN amplification (MNA) in paediatric neuroblastoma (NB) patients. METHODS: A total of 104 patients with NB were retrospectively included. We constructed a nomogram to predict MNA based on radiomics signatures, clinical and radiological features. The multivariable logistic regression and the least absolute shrinkage and selection operator (LASSO) were used for feature selection. Radiomics models are constructed using decision trees (DT), logistic regression (LR) and support vector machine (SVM) classifiers. A clinical-radiological (C-R) model was developed using clinical and radiological features. A clinical-radiological-radiomics (C-R-R) model was developed using the C-R model of the best radiomics model. The prediction performance was verified by receiver operating characteristic (ROC) curve analysis, calibration curve analysis and decision curve analysis (DCA) in the training and validation cohorts. RESULTS: The present study showed that four radiomics signatures were significantly correlated with MNA. The SVM classifier was the best model of radiomics signature. The C-R-R model has the best discriminant ability to predict MNA, with AUCs of 0.860 (95% CI, 0.757-0.963) and 0.824 (95% CI, 0.657-0.992) in the training and validation cohorts, respectively. The calibration curve indicated that the C-R-R model has the goodness of fit and DCA confirms its clinical utility. CONCLUSION: Our research provides a non-invasive C-R-R model, which combines the radiomics signatures and clinical and radiological features based on 18F-FDGPET/CT images, shows excellent diagnostic performance in predicting MNA, and can provide useful biological information with stratified therapy. CRITICAL RELEVANCE STATEMENT: Radiomic signatures of 18F-FDG-based PET/CT can predict MYCN amplification in neuroblastoma. KEY POINTS: • Radiomic signatures of 18F-FDG-based PET/CT can predict MYCN amplification in neuroblastoma. • SF, LDH, necrosis and TLG are the independent risk factors of MYCN amplification. • Clinical-radiological-radiomics model improved the predictive performance of MYCN amplification.

Dysregulated RUNX1 Predicts Poor Prognosis by Mediating Epithelialmesenchymal Transition in Cervical Cancer.

OBJECTIVE: Runt-related transcription factor 1 (RUNX1) has been proven to be over-expressed and vital in many malignancies. However, its role in cervical cancer is still unclear. METHODS: Some online databases (Oncomine, GEPIA, UALCAN, LinkedOmics, and others) were used to explore the expression level, prognostic significance, and gene mutation characteristics of RUNX1 in cervical cancer. The protein levels of RUNX1 in cervical cancer were measured by immunohistochemistry (IHC). The functional changes of cervical cancer cells were measured in vitro after decreasing RUNX1. RESULTS: Bioinformatic results revealed that RUNX1 was upregulated in cervical cancer compared to normal tissues. Moreover, over-expression of RUNX1 was significantly correlated with cervical cancer patients' clinical parameters (e.g., individual cancer stages, patients' age, nodal metastasis status, and others). Meanwhile, functional enrichment analysis of RUNX1-related genes indicated that RUNX1 was mainly involved in the epithelial-mesenchymal transition (EMT) process in cervical cancer. Furthermore, RUNX1 may be upregulated by hsamiR-616-5p and hsa-miR-766 identified by miRDB, TargetScan, and miRWalk. Finally, RUNX1 was upregulated in cervical cancer compared to normal tissues by IHC in collected cervical cancer samples. The invasion and migration abilities of cervical cancer cells were significantly reduced by repressing EMT after knocking down RUNX1 in vitro. CONCLUSION: RUNX1 was highly expressed in cervical cancer, and upregulated RUNX1 could significantly promote the invasive abilities of cervical cancer cells by inducing EMT. Therefore, RUNX1 may be a potential biomarker for early diagnosis and targeted therapy of cervical cancer.

Clinical value of 68Ga-DOTA-SSTR PET/CT in the diagnosis and detection of neuroendocrine tumors of unknown primary origin: a systematic review and meta-analysis.

BACKGROUND: The ability of 68Ga-DOTA-SSTR to detect the primary sites of neuroendocrine tumors (NETs) remains undetermined, and the clinical benefit of this imaging agent is not clear. PURPOSE: To evaluate the diagnostic accuracy of 68Ga-DOTA-SSTR for carcinoma unknown primary (CUP) neuroendocrine tumors and to further analyze the detection rate of 68Ga-DOTA-SSTR for primary and metastatic sites. MATERIAL AND METHODS: A comprehensive literature search of PubMed/MEDLINE and ScienceDirect was performed in October 2019 in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. We critically reviewed all studies based on the PICOS criteria. QUADAS-2 was used to evaluate the quality of the methodology of the included studies. RESULTS: A total of 10 studies (484 patients, mean age = 56.6 ± 4.3 years) were included in the study. The pooled sensitivity and specificity of 68Ga-DOTA-SSTR in identifying CUP-NETs were 82% and 55%, respectively. The area under the receiver operating characteristic curve was 69%. Regarding metastasis sites, 68Ga-DOTA-SSTR found the most metastases in the liver (57.9%), followed by the lymph nodes (22.8%), bones (12.8%), lung (2.8%), and others (1.7%). The pooled detection rate of 68Ga-DOTA-SSTR for CUP-NETs was 61%. CONCLUSION: The present study demonstrated the high diagnostic sensitivity of 68Ga-DOTA-SSTR for CUP-NETs. 68Ga-DOTA-SSTR PET/CT was highly effective in locating the primary and metastatic sites of CUP-NETs.

Roles of F-18-Fluoro-2-Deoxy-Glucose PET/Computed Tomography Scans in the Management of Post-Transplant Lymphoproliferative Disease in Pediatric Patient.

Post-transplant lymphoproliferative disease is a well-known complication in transplant recipients. Evaluating the extent and stage of disease is important for management and follow-up. As a combination of anatomic and functional imaging, PET/CT is a sensitive and specific tool to stage and detect occult disease compared with conventional imaging. PET/CT also has a role in monitoring treatment response. Although PET/CT has been shown to be potentially useful in adults, evidence in children is insufficient. This review provides an overview of the use of PET/CT in post-transplant lymphoproliferative disease, especially in pediatric patients.

Hepatopulmonary Syndrome Mimics Pulmonary Embolism on Pulmonary Ventilation/Perfusion SPECT/CT Study.

A 64-year-old woman with a history of cirrhosis and progressive difficulty breathing underwent pulmonary ventilation/perfusion SPECT to evaluate possible pulmonary embolism. The images demonstrated multiple mismatched ventilation/perfusion defects in both lungs, suggesting pulmonary embolism. However, there was also Tc-MAA radioactivity in the brain and bilateral kidney, with a right-to-left shunting rate of 8.8%. In addition, CT pulmonary angiography did not demonstrate embolus. The findings indicated that perfusion defects were caused by hepatopulmonary syndrome.

Neural metabolic activity in idiopathic tinnitus patients after repetitive transcranial magnetic stimulation.

BACKGROUND: The central mechanism of idiopathic tinnitus is related to hyperactivity of cortical and subcortical auditory and non-auditory areas. Repetitive transcranial magnetic stimulation (rTMS) is a well-tolerated, non-invasive potential treatment option for tinnitus. AIM: To investigate the changes of neural metabolic activity after rTMS in chronic idiopathic tinnitus (IT) patients. METHODS: Eleven patients underwent rTMS (1 Hz, 90% motor threshold, 1000 stimuli/day for consecutive 10 d) on the left temporoparietal region cortex. Tinnitus handicap inventory (THI) and visual analogue score (VAS) were assessed at baseline and posttreatment. All patients underwent 18F-fluorodeoxyglucose (FDG) positron emission tomography to evaluate the neural metabolic activity. Data were preprocessed using statistical parametric mapping and Gretna software to extract the regions of interest (ROIs). The correlation between brain areas involved and THI scores was analyzed. RESULTS: Baseline and posttreatment parameters showed no significant difference regarding THI score (t = 1.019, P = 0.342 > 0.05) and VAS (t = 0.00, P = 1.0 > 0.05). Regions with the highest FDG uptake were the right inferior temporal gyrus (ITG), right parahippocampa gyrus (PHG), right hippocampus, rectus gyrus, left middle frontal gyrus, and right inferior frontal gyrus in IT patients. After rTMS treatment, IT patients showed increased activities in the right PHG, right superior temporal gyrus, right superior frontal gyrus, anterior insula, left inferior parietal lobule, and left precentral gyrus, and decreased activities in the left postcentral gyrus and left ITG. The ROIs in the right parahippocampa gyrus and right superior frontal gyrus were positively correlated with THI scores (r = 0.737, P = 0.037 < 0.05; r = 0.735, P = 0.038 < 0.05). CONCLUSION: Our study showed that 1-Hz rTMS directed to the left temporo-parietal junction resulted no statistically significant symptom alleviation. After treatment, brain areas of the limbic and prefrontal system showed high neutral metabolic activity. The auditory and non-auditory systems together will be the target for rTMS treatment.

Tim3/galectin-9 alleviates the inflammation of TAO patients via suppressing Akt/NF-kB signaling pathway.

Thyroid-associated ophthalmopathy (TAO) is an autoimmune disease. Studies showed that T helper 1 (Th1), Th2, and Th17 cells play important roles in the pathology of TAO. Tim-3 and its only known ligand Galectin-9 (Gal-9) is related to the suppression of Th1 and Th17 cytokine secretion. This study aims to investigate the role of Tim3/Gal-9 in the inflammatory response of TAO. In this study, the levels of Tim3, Gal-9, and cytokines of Th1 (TNF-α and IFN-γ), Th2 (IL-4), and Th17 (IL-17) cells were analyzed in the blood samples of TAO patients and healthy controls as well as in orbital fibroblasts. Tim3 overexpression and Gal-9 neutralizing antibody were used in TAO and LPS-stimulated control orbital fibroblasts to further investigate the role and mechanism of Tim3/Gal-9 on the inflammation of TAO. We found Tim3 and Gal-9 expression was significantly downregulated in TAO patients and further lower in active TAO than inactive TAO or controls. Th1, Th2, and Th17 cytokines were all increased in TAO patients. Th1 and Th17 cytokines were higher in active TAO patients than in inactive TAO patients, while Th2 cytokines were enhanced in inactive TAO. Tim3 overexpression decreased the levels of Th1 and Th17 cytokines, but not Th2 cytokine in TAO or LPS-stimulated control orbital fibroblasts. These effects were abrogated by Gal-9 neutralizing antibody. Moreover, Tim3 reduced the levels of p-Akt and p-p65 in TAO or LPS-induced control orbital fibroblasts that were reversed by Gal-9 blocking. In conclusion, Tim3/Gal-9 alleviates the inflammation of TAO patients via suppressing Akt/NF-κB signaling pathway.

Incidence of vascular anomalies and variants associated with unilateral venous pulsatile tinnitus in 242 patients based on dual-phase contrast-enhanced computed tomography.

BACKGROUND: A comprehensive assessment of various vascular anomalies and variants associated with venous pulsatile tinnitus (PT) by radiography is essential for therapeutic planning and improving the clinical outcome. This study evaluated the incidence of various vascular anomalies and variants on the PT side and determined whether these lesions occurred as multiple or single entities. METHODS: The dual-phase contrast-enhanced computed tomography images of 242 patients with unilateral venous PT were retrospectively reviewed. The vascular anomalies and variants on the symptomatic and asymptomatic sides were analyzed, and the incidences of anomalies or variants on each side were compared. The number of anomalies and variants on the symptomatic side in each patient was calculated. RESULTS: (1) A total 170 patients (170/242) had more than one anomaly or variant on the symptomatic side, and 58 patients (58/242) had a single lesion on tomography. (2) There was a statistically significant difference in the incidence of dehiscent sigmoid plate (P = 0.000), lateral sinus stenosis (P = 0.014), high jugular bulb (P = 0.000), sigmoid sinus diverticulum (P = 0.000), jugular bulb diverticulum (P = 0.000), dehiscent jugular bulb (P = 0.000), and a large emissary vein (P = 0.006) between the symptomatic and asymptomatic sides. (3) Dehiscent sigmoid plate (86.4%) was the most frequent lesion on the symptomatic side, followed by lateral sinus stenosis (55.8%), high jugular bulb (47.1%), sigmoid sinus diverticulum (34.3%), jugular bulb diverticulum (13.6%), dehiscent jugular bulb (13.6%), large emissary vein (4.1%), sinus thrombosis (1.2%), and petrosquamosal sinus (0.8%). CONCLUSIONS: Various vascular anomalies and variants occur more frequently on the venous PT side. Preliminary findings suggest that venous PT patients may have multiple vascular anomalies or variants on the symptomatic side.

Incidental finding of Tc-99m MDP bone scintigraphy in a case of X-linked spondyloepiphyseal dysplasia tarda.

A 26-year-old male presented with a history of backache and multijoint pain over the preceding 15 years. Bone scintigraphy demonstrated a short spine in addition to abnormally increased activity in multiple joints. The patient was eventually diagnosed to have X-linked spondyloepiphyseal dysplasia tarda.

Comparison of different diagnostic methods for differentiating biliary atresia from idiopathic neonatal hepatitis.

AIM: To retrospectively analyze different methods in differentiating biliary atresia from idiopathic neonatal hepatitis. METHODS: Sixty-nine infants with cholestatic jaundice and final diagnosis of idiopathic neonatal hepatitis (INH) and biliary atresia (BA) were studied retroprospectively from January 2004 to December 2006. A thorough history and physical examination were undertaken. All cases underwent abdominal magnetic resonance cholangiography (MRCP), ultrasonography (US), hepatobiliary scintigraphy (HBS), HBS single-photon emission computer tomography (HBS SPECT), and operation or percutaneous liver biopsy. The accuracy, sensitivity, specificity, and predictive values of these various methods were compared. RESULTS: There were 39 girls and 30 boys, among whom 35 had INH (age, 61+/-17 days) and 34 had BA (age, 64+/-18 days). The mean age at onset of jaundice was significantly lower in cases of BA when compared to INH cases (9+/-13 vs. 20+/-21 days; P=.032). The diagnostic accuracy of different methods was as follows: liver biopsy, 97.1%; HBS SPECT, 91.30%; MRCP, 71.01%; HBS, 66.67%; US, 65.22%. CONCLUSION: Our results indicate that biopsy of the liver is considered as the most reliable method to differentiate INH from BA. The accuracy of HBS SPECT is higher than that of MRCP, HBS, and US. There was no significant difference in diagnostic accuracy among MRCP, HBS, and US.

Primary osteogenic sarcoma of breast detected on Tc-99m MIBI scintigraphy and Tc-99m MDP skeletal scintigraphy.

A 64-year-old woman presented with a painless breast mass. Tc-99m methoxyisobutylisonitrile scintigraphy of both breasts showed a local area of abnormal uptake in the left breast in 5 min and 2 h. A skeletal scan showed very intense concentration of activity in the primary breast tumor in the left breast. A left mastectomy and an axillary dissection were performed. The predominant histologic type of the mass was an osteosarcoma, and the diagnosis of a primary osteogenic sarcoma of the breast was made. Primary osteogenic sarcoma of the breast is rare and represents less than 1% of all primary breast malignancies.

[The diagnostic value of FDG coincidence imaging combined with serum tumor marker assays for pulmonary lesions].

OBJECTIVE: To evaluate the performance of 18F-FDG three-head tomography with coincidence imaging and serum tumor marker assays in identifying lung lesions in 104 patients with abnormal findings on chest X-ray or computer tomography. METHODS: A prospective evaluation of 18F-FDG coincidence imaging and the measurement of 3 serum markers for lung cancer ( carcinoembryonic antigen, CYFRA21-1 and neuron specific enolase) were performed within one week in 104 inpatients with suspected lung malignancy. All images were analyzed visually. It was considered positive for malignancy if the 18F-FDG uptake was increased relative to that in the adjacent lung tissue, and was focal. The serum tumor marker test was considered positive for malignancy if the serum level of at least one marker was elevated. RESULTS: 66 patients were proven to have lung cancer by pathology, and 38 patients had benign lung diseases. The sensitivity, specificity, accuracy of 18F-FDG coincidence imaging and serum tumor markers in assessing lung cancers were 80. 0% , 77. 2% , 77. 9% and 56. 0% , 60. 9%, 64. 4% , respectively. 18F-FDG coincidence images in assessing lung lesions showed significantly higher sensitivity, specificity and accuracy than serum tumor markers. Four patients with lung cancer had negative findings on 18F-FDG coincidence images but showed positive serum markers. CONCLUSION: 18F-FDG coincidence imaging is a powerful tool for evaluating patients with lung lesions suggestive of malignancy. Although the determination of serum marker levels is less accurate than 18F-FDG coincidence imaging, the combination of a positive 18F-FDG coincidence result and positive tumor markers may be helpful in improving the diagnosis of lung cancers.