Study on the Prognostic Values of TTC36 Correlated with Immune Infiltrates and Its Methylation in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) remains an incurable disease with a very poor clinical outcome. The purpose of this article was to investigate whether the expression or methylation of tetrapeptide repeat domain 36 (TTC36) could be used as a prognostic marker in hepatocellular carcinoma. TCGA database was used to obtain information on HCC gene expression and the associated clinical features of HCC patients. Differentially expressed genes (DEGs) were screened between 374 HCC specimens and 50 nontumor specimens. The expression and prognostic value of TTC36 were analyzed. The correlations between TTC36 and cancer immune infiltrates were investigated via TIMER. In this study, HCC specimens and nontumor specimens were compared and 35 DEGs were found between them. Among the 35 DEGs, the expression of TTC36 was significantly reduced in HCC samples compared with nontumor samples. Survival tests revealed that patients with low TTC36 expression had a shorter overall survival than patients with high TTC36 expression. TTC36 was found to be an independent predictive factor for HCC in both univariate and multivariate regression analyses. TTC36 was negatively regulated by TTC36 methylation, leading to its low expression in HCC tissues. Immune analysis revealed that TTC36 expression has significant correlations with B cell, T cell CD4+, neutrophil, macrophage, and myeloid dendritic cell. Finally, TTC36 expression was dramatically reduced in HCC cells, and overexpression greatly suppressed HCC cell proliferation and invasion, according to our experimental results. Overall, our data suggested that TTC36 could be applied as a prognostic marker for predicting outcome and immune infiltration in HCC.

Construction of a target MSNs drugcarrier loaded with siRNAGLI1 and siRNASMO aim at hedgehog signal pathway and the pharmacodynamic study of drug-carriers in the treatment of leukemia stem cells.

Leukemia stem cells (LSCs) are responsible for leukemia initiation and targeting LSCs is one strategy to treat this disease. This study aims to target LSCs using multi-siRNA loaded antibodies modified with mesoporous silica nanoparticles (MSNs). Here, both siRNAGLI1 and siRNASMO were loaded in an anti-CD34 antibody modified with MSNs, and then, the MSN@siRNAGLI1@Antibody + MSNs@siRNASMO@Antibody cocktail was used to target LSCs. Expression levels of BCL-2 in LSCs were significantly reduced whereas Bax expression was significantly increased after treatment with nano-drug carriers. In addition, these nano-drug carriers also effectively induced the apoptosis of LSCs. The MSNs@siRNAGLI1@Antibody + MSNs@siRNASMO@Antibody cocktail significantly inhibited LSCs. In short, we constructed two target MSN nano-drug carriers where loaded siRNAs can be used in a chemotherapeutic drug cocktail to improve the treatment of leukemia.

Differential Expression and Diagnostic Significance of Pre-Albumin, Fibrinogen Combined with D-Dimer in AFP-Negative Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most malignant cancers with high morbidity and mortality. Nowadays, AFP-negative hepatocellular carcinoma (AFP-NHCC) has been found in many HCC patients and AFP analysis can't be used to screen HCC in these cases. In this study, we have examined the expression patterns of pre-albumin (PA), fibrinogen, D-Dimer and their clinical significance in AFP-NHCC. We recruited 214 AFP-NHCC patients and 210 controls in the study. PA, fibrinogen and D-Dimer levels were detected by turbidimetry, clauss and immunoturbidimetry methods, respectively. Serum PA levels were significantly lower in AFP-NHCC (84.5 ± 24.7 mg/L) than that in the controls (240.6 ± 59.4 mg/L, P < 0.05). For plasma fibrinogen levels, there was no difference between the controls (2.9 ± 0.7 g/L) and AFP-NHCC (2.5 ± 0.7 g/L). Compared with AFP-NHCC (0.8 ± 0.2 mg/L), plasma D-Dimer levels were significantly lower in controls (0.1 ± 0.0 mg/L, P < 0.05). The levels of PA, fibrinogen and D-Dimer were significantly correlated with differentiation (P < 0.01), and the PA and D-Dimer values were correlated with TNM stage (P < 0.05). Moreover, PA levels were correlated with tumor size (P = 0.034). Receiver operating characteristic curve (ROC) analyses elaborated that combination of PA, fibrinogen and D-Dimer possessed a higher sensitivity (93.4%) for differentiating AFP-NHCC from the controls, but the diagnostic specificity was reduced due to the combination of fibrinogen. After adjusting for all significant outcome predictors of the univariate logistic regression analysis, low levels of PA and high levels of D-Dimer were remained independent unfavorable outcome predictors (P < 0.05). Our data suggested that the expression levels of PA, fibrinogen and D-Dimer played critical roles in AFP-NHCC tumorigenesis. Moreover, PA and D-Dimer might be considered as potential diagnostic indicators in AFP-NHCC.

The diagnostic and prognostic significance of long noncoding RNAs expression in thyroid cancer: A systematic review and meta-analysis.

OBJECTIVE: Thyroid cancer (TC) is the most common malignant endocrine-related cancer with an increasing trend worldwide. Therefore, it's in urgent need to find new markers for prognosis and diagnosis. Many long noncoding RNAs (lncRNAs) have been reported to be aberrantly expressed in TC, and may serve as biomarkers. Therefore, we performed this meta-analysis to systematically summarize the relationship between lncRNA expressions and TC. METHODS: Sources from PubMed, Embase and Web of Science were searched. A total of 16 eligible studies including 15 on clinicopahology, 5 on prognosis and 6 on diagnosis were enrolled in our meta-analysis. Revman5.3 and Stata11.0 Software were used to conduct the meta-analysis. RESULTS: For diagnostic value, lncRNAs could discriminate between TC and the normal, and yield a high overall sensitivity and specificity (0.80, 95% CI: 0.75-0.84; 0.80, 95% CI: 0.70-0.87). Meanwhile, their sensitivity and specificity were 0.74 (95% CI: 0.59-0.85) and 0.81 (95% CI: 0.73-0.88) respectively, when used to differentiate patients with lymph node metastasis (LNM) from without LNM. The summary receiver operator characteristic curve (sROC) showed that lncRNAs could be considered as valuable diagnostic markers for distinguishing TC patients from the normal (AUC = 0.84) and TC patients with LNM from TC patients without LNM (AUC = 0.85). CONCLUSIONS: In summary, our meta-analysis suggested that lncRNAs could function as potential diagnostic markers for TC and predict the LNM. In addition, the systematic review elaborated that lncRNAs might be as prognostic indicators in TC.

DNA Methylation Analysis of the SHOX2 and RASSF1A Panel in Bronchoalveolar Lavage Fluid for Lung Cancer Diagnosis.

Introduction: Currently the majority of lung cancer patients are diagnosed as advanced diseases for no sensitive and specific biomarkers exist, noninvasive biomarkers with high sensitivity and specificity are urgently needed in lung cancer diagnosis. Bronchoscopy is a standard procedure of the diagnostic work-up of patients with suspected lung cancer despite of the limited diagnostic accuracy. Besides, epigenetic changes through DNA methylation play an important role in tumorigenesis. Thus, we examined the aberrant methylation of the SHOX2 and RASSF1A in bronchoalveolar lavage fluid (BALF) in comparing with conventional cytology examination and serum CEA in order to evaluate the new diagnostic method. Patients and Methods: BALF and serum samples were collected from 322 patients at the time of diagnosis, 284 of them were pathologically confirmed lung cancer, 35 were benign lung diseases and 3 were malignancies in other systems. For all of the 322 patients, the methylation status of the SHOX2 and RASSF1A gene were detected by a new RT-PCR platform and then confirmed by sanger sequencing. Serum CEA were detected using electrochemiluminescence immunoassay. Results: Profiling data showed the consistency of RT-PCR and sanger sequencing in detecting the methylation of the SHOX2 and RASSF1A. Besides, the combination of SHOX2 and RASSF1A methylation in BALF yielded a diagnostic sensitivity of 81.0% and specificity of 97.4%. When compared with established cytology examination (sensitivity: 68.3%, specificity: 97.4%) and serum biomarker carcinoembryonic antigen (CEA) (sensitivity: 30.6%, specificity: 100.0%), the SHOX2 and RASSF1A methylation panel showed the highest diagnostic efficiency. Notably, the combination of cytology and the SHOX2 and RASSF1A methylation panel could significantly improve the diagnostic efficacy. Conclusion: The methylation analysis of the SHOX2 and RASSF1A panel in BALF with RT-PCR achieved a satisfactory sensitivity and specificity in lung cancer diagnosis, especially in an early stage. It could be used as a promising noninvasive biomarker for auxiliary diagnosis of lung cancer.

Biomarkers for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. The HCC diagnosis is usually achieved by biomarkers, which can also help in prognosis prediction. Furthermore, it might represent certain therapeutic interventions through some combinations of biomarkers. Here, we review on our current understanding of HCC biomarkers.

IQGAP1 Mediates Hcp1-Promoted Escherichia coli Meningitis by Stimulating the MAPK Pathway.

Escherichia coli-induced meningitis remains a life-threatening disease despite recent advances in the field of antibiotics-based therapeutics, necessitating continued research on its pathogenesis. The current study aims to elucidate the mechanism through which hemolysin-coregulated protein 1 (Hcp1) induces the apoptosis of human brain microvascular endothelial cells (HBMEC). Co-immunoprecipitation coupled with mass spectrometric (MS) characterization led to the identification of IQ motif containing GTPase activating protein 1 (IQGAP1) as a downstream target of Hcp1. IQGAP1 was found to be up-regulated by Hcp1 treatment and mediate the stimulation of HBMEC apoptosis. It was shown that Hcp1 could compete against Smurf1 for binding to IQGAP1, thereby rescuing the latter from ubiquitin-dependent degradation. Subsequent study suggested that IQGAP1 could stimulate the MAPK signaling pathway by promoting the phosphorylation of ERK1/2, an effect that was blocked by U0126, an MAPK inhibitor. Furthermore, U0126 also demonstrated therapeutic potential against E. coli meningitis in a mouse model. Taken together, our results suggested the feasibility of targeting the MAPK pathway as a putative therapeutic strategy against bacterial meningitis.

Identification of A Panel of Serum microRNAs as Biomarkers for Early Detection of Lung Adenocarcinoma.

Introduction: Since currently no sensitive and specific biomarkers for early detection of lung adenocarcinoma (AD) exist and the majority of AD patients are diagnosed at late stages of disease, the development of effective screening tests for early-stage lung AD is urgently needed. Serum microRNAs (miRNAs) have been documented as novel noninvasive biomarkers in tumor diagnosis; thus, we studied the profile of serum miRNA in AD patients in order to identify the differentially expressed miRNAs as potential biomarkers for early detection of AD. Patients and Methods: Serum samples were collected from 180 AD patients and 180 age- and sex-matched healthy controls. Serum miRNA profiling was performed by low-density array (LDA) using RNA extracted from blood samples of 20 patients and 20 controls. To validate the selected miRNAs, a stem-loop based RT-qPCR assay was used and serum samples from 160 patients and 160 controls were examined. Results: Profiling data showed 11 differentially expressed miRNAs in the serum samples from AD patients compared with the controls. Among them, 6 selected miRNAs in AD patients, including miR-103, miR-146a, miR-151, miR-21, miR-221, miR-222, and miR-223, were validated by RT-qPCR. In particular, the top three, miR-146a, miR-222, and miR-223, were confirmed to be significantly expressed in stage I/II AD patients compared with healthy controls. Conclusion: A panel of miRNAs with miR-146a, miR-222 and miR-223 could be used as potential noninvasive biomarkers for early detection of AD.