BackgroundDysfunctions of long non-coding RNA (lncRNAs) have been associated with the initiation and progression of hepatocellular carcinoma (HCC), but the clinicopathologic significance and potential role of lncRNA PTTG3P (pituitary tumor-transforming 3, pseudogene) in HCC remains largely unknown.MethodsWe compared the expression profiles of lncRNAs in 3 HCC tumor tissues and adjacent non-tumor tissues by microarrays. In situ hybridization (ISH) and quantitative real-time polymerase chain reaction (qRT-PCR) were applied to assess the level of PTTG3P and prognostic values of PTTG3P were assayed in two HCC cohorts (n = 46 and 90). Artificial modulation of PTTG3P (down- and over-expression) was performed to explore the role of PTTG3P in tumor growth and metastasis in vitro and in vivo. Involvement of PTTG1 (pituitary tumor-transforming 1), PI3K/AKT signaling and its downstream signals were validated by qRT-PCR and western blot.ResultsWe found that PTTG3P was frequently up-regulated in HCC and its level was positively correlated to tumor size, TNM stage and poor survival of patients with HCC. Enforced expression of PTTG3P significantly promoted cell proliferation, migration, and invasion in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, PTTG3P knockdown had opposite effects. Mechanistically, over-expression of PTTG3P up-regulated PTTG1, activated PI3K/AKT signaling and its downstream signals including cell cycle progression, cell apoptosis and epithelial-mesenchymal transition (EMT)-associated genes.ConclusionsOur findings suggest that PTTG3P, a valuable marker of HCC prognosis, promotes tumor growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in HCC and might represent a potential target for gene-based therapy.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0841-x) contains supplementary material, which is available to authorized users.
OBJECTIVE Glioma is the most common form of brain tumor and has high lethality. The authors of this study aimed to elucidate the efficiency of preoperative inflammatory markers, including neutrophil/lymphocyte ratio (NLR), derived NLR (dNLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), and prognostic nutritional index (PNI), and their paired combinations as tools for the preoperative diagnosis of glioma, with particular interest in its most aggressive form, glioblastoma (GBM). METHODS The medical records of patients newly diagnosed with glioma, acoustic neuroma, meningioma, or nonlesional epilepsy at 3 hospitals between January 2011 and February 2016 were collected and retrospectively analyzed. The values of NLR, dNLR, PLR, LMR, and PNI were compared among patients suffering from glioma, acoustic neuroma, meningioma, and nonlesional epilepsy and healthy controls by using nonparametric tests. Correlations between NLR, dNLR, PLR, LMR, PNI, and tumor grade were analyzed. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic significance of NLR, dNLR, PLR, LMR, PNI, and their paired combinations for glioma, particularly GBM. RESULTS A total of 750 patients with glioma (Grade I, 81 patients; Grade II, 208 patients; Grade III, 169 patients; Grade IV [GBM], 292 patients), 44 with acoustic neuroma, 271 with meningioma, 102 with nonlesional epilepsy, and 682 healthy controls were included in this study. Compared with healthy controls and patients with acoustic neuroma, meningioma, or nonlesional epilepsy, the patients with glioma had higher values of preoperative NLR and dNLR as well as lower values of LMR and PNI, whereas PLR was higher in glioma patients than in healthy controls and patients with nonlesional epilepsy. Subgroup analysis revealed a positive correlation between NLR, dNLR, PLR, and tumor grade but a negative correlation between LMR, PNI, and tumor grade in glioma. For glioma diagnosis, the area under the curve (AUC) obtained from the ROC curve was 0.722 (0.697-0.747) for NLR, 0.696 (0.670-0.722) for dNLR, 0.576 (0.549-0.604) for PLR, 0.760 (0.738-0.783) for LMR, and 0.672 (0.646-0.698) for PNI. The best diagnostic performance was obtained with the combination of NLR+LMR and dNLR+LMR, with AUCs of 0.777 and 0.778, respectively. Additionally, NLR (AUC 0.860, 95% CI 0.832-0.887), dNLR (0.840, 0.810-0.869), PLR (0.678, 0.641-0.715), LMR (0.837, 0.811-0.863), and PNI (0.740, 0.706-0.773) had significant predictive value for GBM compared with healthy controls and other disease groups. As compared with the Grade I-III glioma patients, the GBM patients had an AUC of 0.811 (95% CI 0.778-0.844) for NLR, 0.797 (0.763-0.832) for dNLR, 0.662 (0.622-0.702) for PLR, 0.743 (0.707-0.779) for LMR, and 0.661(0.622-0.701) for PNI. For the paired combinations, NLR+LMR demonstrated the highest accuracy. CONCLUSIONS The NLR+LMR combination was revealed as a noninvasive biomarker with relatively high sensitivity and specificity for glioma diagnosis, the differential d...
We aimed to study whether red blood cell distribution width (RDW) could be one of the variables determining the extent of liver fibrosis and inflammation in patients with biopsy-proven hepatitis B.A total of 446 hepatitis B virus-infected patients who underwent liver biopsy were divided into 2 groups: absent or mild and moderate–severe according to the severity of liver fibrosis and inflammation. The independent variables that determine the severity of liver fibrosis and inflammation were explored.RDW values increased with progressive liver fibrosis and inflammation. After adjustments for other potent predictors, liver fibrosis (moderate–severe) was independently associated with RDW, platelet, and albumin (odds ratio = 1.121, 0.987, and 0.941, respectively), whereas increased odds ratios of significant inflammation were found for RDW, alanine aminotransferase, albumin, and PLT (odds ratio = 1.146, 1.003, 0.927, and 0.990, respectively). The sensitivity and specificity of model A were 70.0% and 62.9% for detection of significant liver fibrosis [area under the receiver-operating characteristic curve (AUC) = 0.713, P < .001]. The sensitivity and specificity of model B were 66.1% and 79.4% for predicting advanced liver inflammation (AUC = 0.765, P < .001). Compared with preexisting indicators, model A achieved the highest AUC, whereas model B showed a higher AUC than RDW to platelet ratio (0.670, P < .001) and FIB-4 (0.740, P = .32).RDW may provide a useful clinical value for predicting liver fibrosis and necroinflammation in hepatitis B-infected patients with other markers.
Pregenomic RNA (pgRNA) is a direct transcription product of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), and it plays important roles in viral genome amplification and replication. This study was designed to investigate whether serum pgRNA is a strong alternative marker for reflecting HBV cccDNA levels and to analyze the correlation between serum pgRNA, serum HBV DNA, and hepatitis B surface antigen (HBsAg). A total of 400 HBV-infected patients who received nucleos(t)ide analog (NA) therapy with different clinical outcomes were involved in this research. Case groups included asymptomatic hepatitis B virus carrier (ASC), chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC) patients, with 100 patients in each group. The results showed that the levels of HBV pgRNA had significant differences between these 4 groups. Serum pgRNA levels correlated well with serum HBV DNA and HBsAg levels (HBV pgRNA levels versus HBV DNA levels, r = 0.58, P < 0.001; HBV pgRNA levels versus HBsAg levels, r = 0.47, P < 0.001). In addition, we focused on the 108 HBV-infected patients with HBV DNA levels of <500 IU/ml; it was surprising to find that in 17.57% (13/74) of cases, HBV pgRNA could be detected even when the HBV DNA level was below 20 IU/ml. In conclusion, HBV pgRNA levels in serum can be a surrogate marker for intrahepatic HBV cccDNA compared with serum HBV DNA and HBsAg. The detection of serum HBV pgRNA levels may provide a reference for clinical monitoring of cccDNA levels and the selection of appropriate timing for discontinuing antiviral therapy, especially when HBV DNA levels are below the detection limit.
We found that the JETLIA-962 chemiluminescence analyzer was of great value in diagnosis of liver fibrosis. Combining five indices improved the diagnostic efficiency and reduced the incidences of unnecessary liver biopsies. Two logistic regression equations established may be helpful in diagnosing liver fibrosis and early cirrhosis, which need to be further evaluated.
BackgroundTo determine reference intervals for serum levels of human epididymis protein 4 (HE4) in Chinese women.MethodsIn this multicenter (n = 9) study, 618 healthy women, 767 patients with non-malignant diseases, and 951 patients with malignant tumors were enrolled. Serum levels of HE4 were measured in all patients using electrochemiluminescence immunoassays. The influence of age, menopause, malignancy status and other characteristics on the levels of HE4 was evaluated using univariate and multivariate analyses. Confidence intervals (2.5–97.5 %) were determined in different populations.ResultsThere were significant differences in HE4 levels among groups with different ages, menopause or malignancy status. Higher levels of HE4 were detected in elder compared to younger, post- compare to pre- menopause and malignant compared to benign subjects. Multivariate analysis showed that menopause and malignancy status, as well as smoking and pelvic masses were independent factors involved in serum HE4 levels. In pre-menopause stage, the reference ranges of HE4 level were 29.30–68.79, 28.12–1284.83 and 34.75–981.91 pmol/L in healthy, benign and malignant populations, respectively. In post-menopause stage, the reference ranges are 35.96–114.43, 39.11–2208.70 and 39.40–1678.13 pmol/L for those populations.ConclusionsThe present study has established the reference intervals of HE4 levels in pre- and post-menopause populations with different malignancy status.Electronic supplementary materialThe online version of this article (doi:10.1186/s13048-015-0201-z) contains supplementary material, which is available to authorized users.
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