CircDCAF8 promotes the progression of hepatocellular carcinoma through miR-217/NAP1L1 Axis, and induces angiogenesis and regorafenib resistance via exosome-mediated transfer.

BACKGROUND: Circular RNAs (circRNAs), which are a new type of single-stranded circular RNA, have significant involvement in progression of many diseases, including tumors. Currently, multiple circRNAs have been identified in hepatocellular carcinoma (HCC). Our study aims to investigate the function and mechanism of circDCAF8 in HCC. METHODS: The expression of circDCAF8 (hsa_circ_0014879) in HCC and para-carcinoma tissue samples was determined using quantitative real-time polymerase chain reaction (qRT-PCR). The biological function of circDCAF8 in HCC was confirmed by experiments conducted both in vitro and in vivo. And the relationship between circDCAF8, miR-217 and NAP1L1 was predicted by database and verified using qRT-PCR, RNA-binding protein immunoprecipitation (RIP) and dual-luciferase reporter assays. Exosomes isolated from HCC cells were utilized to assess the connection of exosomal circDCAF8 with HCC angiogenesis and regorafenib resistance. RESULTS: CircDCAF8 is upregulated in HCC tissues and cell lines, and is linked to an unfavourable prognosis for HCC patients. Functionally, circDCAF8 was proved to facilitate proliferation, migration, invasion and Epithelial-Mesenchymal Transformation (EMT) in HCC cells. Animal examinations also validated the tumor-promoting characteristics of circDCAF8 on HCC. Besides, exosomal circDCAF8 promoted angiogenesis in HUVECs. Mechanistically, circDCAF8 interacted with miR-217 and NAP1L1 was a downstream protein of miR-217. CircDCAF8 promoted NAP1L1 expression by sponging miR-217. In addition, exosomes may transfer circDCAF8 from regorafenib-resistant HCC cells to sensitive cells, where it would confer a resistant phenotype. CONCLUSION: CircDCAF8 facilitates HCC proliferation and metastasis via the miR-217/NAP1L1 axis. Meanwhile, circDCAF8 can promote angiogenesis and drive resistance to regorafenib, making it a viable therapeutic target for HCC patients.

M2 macrophage-secreted exosomes promote metastasis and increase vascular permeability in hepatocellular carcinoma.

BACKGROUND: Metastasis is a key feature of malignant tumors and significantly contributes to their high mortality, particularly in hepatocellular carcinoma (HCC). Therefore, it is imperative to explore the mechanism of tumor metastasis. Recently, tumor-associated macrophages (TAMs) have been demonstrated to promote tumor progression, while TAM-derived molecules involved in HCC metastasis warrant further investigation. METHODS: THP-1 was treated with IL-4 (Interleukin-4) and IL-13 (Interleukin-13) for M2 polarized macrophages. Exosomes derived from M2 macrophages were characterized. Then, HCC cells or human umbilical vein endothelial cells (HUVECs) were co-cultured with M2 macrophages or treated with M2 macrophage-secreted exosomes. Next, Transwell®, Scratch assay, tube formation, and endothelial permeability assays were performed. Moreover, RT-PCR, western blotting, immunofluorescence, and ELISA were used to assess mRNA and protein expression levels. Finally, the miRNA expression profiles of exosomes derived from M2 and M0 macrophages were analyzed. RESULTS: M2 macrophage infiltration was correlated with metastasis and a poor prognosis in HCC patients. M2-derived exosomes were absorbed by HCC and HUVEC cells and promoted the epithelial-mesenchymal transition (EMT), vascular permeability, and angiogenesis. Notably, MiR-23a-3p levels were significantly higher in M2-derived exosomes and hnRNPA1 mediated miR-23a-3p packaging into exosomes. Phosphatase and tensin homolog (PTEN) and tight junction protein 1 (TJP1) were the targets of miR-23a-3p, as confirmed by luciferase reporter assays. Lastly, HCC cells co-cultured with M2-derived exosomes secreted more GM-CSF, VEGF, G-CSF, MCP-1, and IL-4, which in turn further recruited M2 macrophages. CONCLUSIONS: Our findings suggest that M2 macrophage-derived miR-23a-3p enhances HCC metastasis by promoting EMT and angiogenesis, as well as increasing vascular permeability. Video Abstract.

M2 Macrophage-Derived Exosomes Facilitate HCC Metastasis by Transferring αM ß2 Integrin to Tumor Cells.

BACKGROUND AND AIMS: The development and progression of hepatocellular carcinoma (HCC) is dependent on its local microenvironment. Tumor-associated macrophages (TAMs) are deemed a key factor for the tumor microenvironment and attribute to contribute to tumor aggressiveness. However, the detailed mechanism underlying the pro-metastatic effect of TAMs on HCC remains undefined. APPROACH AND RESULTS: The present study proved that TAMs were enriched in HCC. TAMs were characterized by an M2-polarized phenotype and accelerated the migratory potential of HCC cells in vitro and in vivo. Furthermore, we found that M2-derived exosomes induced TAM-mediated pro-migratory activity. With the use of mass spectrometry, we identified that integrin, αM ß2 (CD11b/CD18), was notably specific and efficient in M2 macrophage-derived exosomes (M2 exos). Blocking either CD11b and/or CD18 elicited a significant decrease in M2 exos-mediated HCC cell metastasis. Mechanistically, M2 exos mediated an intercellular transfer of the CD11b/CD18, activating the matrix metalloproteinase-9 signaling pathway in recipient HCC cells to support tumor migration. CONCLUSIONS: Collectively, the exosome-mediated transfer of functional CD11b/CD18 protein from TAMs to tumor cells may have the potency to boost the migratory potential of HCC cells, thus providing insights into the mechanism of tumor metastasis.

MiR-3174 promotes proliferation and inhibits apoptosis by targeting FOXO1 in hepatocellular carcinoma.

INTRODUCTION: MicroRNAs (miRNAs) have been confirmed to play a crucial part in oncogenesis. Several studies suggested that MiR-3174 act as a tumor promoter in various Malignant neoplasm. However, the biological function of miR-3174 in hepatocellular carcinoma (HCC) still highly unexplored. METHODS: We screened differentially over-expressed miRNAs by The Cancer Genome Atlas (TCGA) and the GEO databases. The expression of miR-3174 in HCC cells and tissues was detected by qRT-PCR. The cellular behaviors of transfected cells were respectively examined by colony formation assays, EdU Assays and flow cytometry. Forkhead box O1 transcription factor (FOXO1) was predicted and confirmed as a direct target of miR-3174 by bioinformatics analysis and dual-luciferase reporter gene assay. RESULTS: MiR-3174 was up-regulated in HCC tissues and cells, and the expression level of it was highly associated with tumor size and Edmondson grade. Our study pioneering validates that upregulated miR-3174 promote cell proliferation and inhibit cell apoptosis in vitro and in vivo. Meanwhile, our study verified that miR-3174 regulate Bim, P21, cyclin D1 and c-MYC expression by directly targeting FOXO1. CONCLUSION: The upregulated miR-3174 promote cell proliferation and inhibit cell apoptosis by downregulating FOXO1 expression in HCC. MiR-3174 may be a novel candidate for targeted delivery of miRNA therapeutics for HCC patients.

5-Hydroxytryptamine Receptor 1D Aggravates Hepatocellular Carcinoma Progression Through FoxO6 in AKT-Dependent and Independent Manners.

Serotonin and its receptors have been shown to play critical regulatory roles in cancer biology. Nevertheless, the contributions of 5-hydroxytryptamine 1D (5-HT1D), an indispensable member of the serotonergic system, to hepatocellular carcinoma (HCC) remain unknown. The present study demonstrated that the 5-HT1D expression level was significantly up-regulated in HCC tissues and cell lines. The 5-HT1D expression level was closely correlated with unfavorable clinicopathological characteristics. Survival analyses show that elevated 5-HT1D expression level predicts poor overall survival and high recurrence probability in HCC patients. Functional studies revealed that 5-HT1D significantly promoted HCC proliferation, epithelial-mesenchymal transition, and metastasis in vitro and in vivo. Mechanistically, 5-HT1D could stabilize PIK3R1 by inhibiting its ubiquitin-mediated degradation. The interaction between 5-HT1D and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) enhanced the expression of FoxO6 through the PI3K/Akt signaling pathway; FoxO6 could also be directly transcriptionally activated by 5-HT1D in an Akt-independent manner. MicroRNA-599 was found to be an upstream suppressive modulator of 5-HT1D. Additionally, 5-HT1D could attenuate tryptophan hydroxylase 1 expression through the PI3K/Akt/cut-like homeobox 1 axis in HCC. Conclusion: Herein, we uncovered the potent oncogenic effect of 5-HT1D on HCC by interacting with PIK3R1 to activate the PI3K/Akt/FoxO6 pathway, and provided a potential therapeutic target for HCC.

circLARP4 induces cellular senescence through regulating miR-761/RUNX3/p53/p21 signaling in hepatocellular carcinoma.

Circular RNAs (circRNAs), a novel class of non-coding RNAs, have emerged as indispensable modulators in human malignancies. Aberrant cellular senescence is a phenotype observed in various cancers. The association of circRNAs with cellular senescence in tumors is yet to determined. Here, we investigated the role of circLARP4 in cellular senescence and cell proliferation in hepatocellular carcinoma (HCC). Downregulated circLARP4 level was observed in HCC tissues and cell lines. Low expression level of circLARP4 independently predicted poor survival outcome. Gain-of-function and loss-of-function assays demonstrated that circLARP4 suppressed HCC cell proliferation, mediated cell cycle arrest and induced senescence in vitro. Levels of p53 and p21, 2 key regulatory molecules in cellular senescence, were increased in circLARP4-overexpressed HCC cells and decreased in circLARP4-silenced HCC cells. In vivo experiments further confirmed the tumor-suppressing activity of circLARP4. Further mechanistic studies showed that circLARP4 dampened HCC progression by sponging miR-761, thereby promoting the expression level of RUNX3 and activating the downstream p53/p21 signaling. Our study revealed the role of circLARP4/miR-761/RUNX3/p53/p21 signaling in HCC progression, providing a potential survival predictor and therapeutic candidate for HCC.

Photocontrolled Healable Structural Color Hydrogels.

Structural color hydrogels with healable capability are of great significance in many fields, however the controllability of these materials still needs optimizing. Thus, this work presents a healable structural color hydrogel with photocontrolling properties. The component parts of the hydrogel are a graphene oxide (GO) integrated inverse opal hydrogel scaffold and a hydrogel filler with reversible phase transition. The inverse opal scaffold provides stable photonic crystal structure and the hydrogel filler is the foundation of healing. Taking advantage of the prominent photothermal conversion efficiency of GO, the healable structural color material is imparted with photocontrolled properties. It is found that the structural color hydrogel shaped in complex patterns can heal under near-infrared (NIR) irradiation. These features indicate that the optical controllable healable structural color hydrogel can be employed in various applications, such as constructing complex objects, repairing tissues, and so on.

PRDM8 exhibits antitumor activities toward hepatocellular carcinoma by targeting NAP1L1.

Hepatocellular carcinoma (HCC) is a major leading cause of cancer mortality worldwide. PRDI-BF1 and RIZ homology domain containing 8 (PRDM8) is a key regulator in neural development and testis steroidogenesis; however, its role in liver carcinogenesis remains to be investigated. In this study, PRDM8 was found to be down-regulated in HCC, which was linked with shorter recurrence-free survival. Lentiviral-based overexpression and knockdown approaches showed that PRDM8 inhibited HCC cell proliferation, migration, and invasion. PRDM8 caused G1/S cell cycle arrest and induced apoptosis. An in vivo tumor model confirmed the antitumor role of PRDM8 in HCC growth and metastasis. Mechanistic study showed that PRDM8 suppressed the PI3K/AKT/mTOR signaling cascade through the regulation of nucleosome assembly protein 1-like 1 (NAP1L1). Conclusion: PRDM8 as a functional tumor suppressor is frequently down-regulated in HCC. Through regulating NAP1L1, PRDM8 inhibits PI3K/AKT/mTOR signaling in HCC. PRDM8 is a potential target for therapies of HCC. (Hepatology 2018).

Precoagulation with microwave ablation for hepatic parenchymal transection during liver partial resection.

PURPOSE: To evaluate the feasibility of precoagulation with microwave ablation (MWA) for hepatic parenchymal transection during liver partial resection. METHODS: A total of 66 eligible patients were enrolled in this double-blind, randomized, controlled study. Patients were randomized to receive either the traditional clamp-crushing method (Control group) or the MWA precoagulation method (MWA group) for hepatic parenchymal transection during liver partial resection. The operative time, hepatic portal occlusion time, intraoperative blood loss and transfusion, postoperative complications and recovery outcomes were compared. RESULTS: Compared to the Control group, the MWA group had significantly less intraoperative blood loss. Fewer red blood cell transfusions were observed in the MWA group but without statistical significance. The MWA group showed significantly higher serum alanine aminotransferase and aspartate aminotransferase levels at day 1 postoperatively, but no differences between the MWA and Control groups were found at days 3 and 7. There were no significant differences in terms of operative time, hepatic portal occlusion time, postoperative total bilirubin levels, human albumin solution consumption or length of hospital stay. Postoperative complications such as impaired renal function, pyrexia, admission to ICU, abscess, biliary leakage, intrahepatic and distant tumor recurrence and in-hospital mortality were comparable between the two groups. CONCLUSION: Precoagulation with MWA reduced intraoperative blood loss with similar postoperative complications, providing a safe, effective, novel alternative for hepatic parenchymal transection during liver partial resection. Additional results from larger series are recommended to confirm these findings.

Using Bioluminescence Turn-On To Detect Cysteine in Vitro and in Vivo.

Cysteine (Cys) is an essential amino acid and plays important roles in many biological processes. Bioluminescence (BL) is advantageous in sensitivity but BL probes that were intentionally developed for the selective detection of Cys were rarely reported. Herein, employing a fast conjugate addition between Cys and acrylic ester, we synthesized a caged BL probe acrylic ester luciferin (1) and used it to selectively detect Cys in vitro and image Cys in living cells and in tumor sites. We envision that, in the future, probe 1 might be used for evaluating the Cys roles in more biological processes.

MicroRNA-873 Promotes Cell Proliferation, Migration, and Invasion by Directly Targeting TSLC1 in Hepatocellular Carcinoma.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has the third highest mortality rate among all cancers. MicroRNAs are a class of endogenous, single-stranded short noncoding RNAs. The purpose of this study was to study the role of microRNA-873 in HCC. METHODS: The expression of miRNA-873 and tumor suppressor in lung cancer 1 (TSLC1) in HCC tissues and cell lines was detected by real-time quantitative RT-PCR (RT-qPCR) or western blot. A CCK-8 assay was used to examine cell proliferation; flow cytometry was used to assess the cell cycle; the Transwell migration assay was used to test for metastasis. Luciferase assays were performed to assess whether TSLC1 was a novel target of miRNA-873. RESULTS: We showed that miRNA-873 was upregulated in HCC tissues and cell lines compared with the normal control. Knockdown of miRNA-873 inhibited the growth and metastasis of HepG2 and accelerated G1 phase arrest, while overexpression of miRNA-873 had the opposite effect. The dual-luciferase reporter assays revealed that TSLC1 was a novel target of miRNA-873. Further study showed that TSLC1 was decreased in HCC tissues and cell lines. There was a negative correlation between the expression levels of TSLC1 and miRNA-873. The effect of miRNA-873 overexpression was neutralized by TSLC1. We also found that miRNA-873 activated the PI3K/AKT/mTOR signaling pathway and promoted HCC. CONCLUSIONS: Our data demonstrated that miRNA-873 promoted HCC progression by targeting TSLC1 and provided a new target for the therapy of HCC.

A Meta-Analysis of the Diagnostic Accuracy of Circular RNAs in Digestive System Malignancy.

BACKGROUND/AIMS: Circular RNAs (circRNAs), a novel class of noncoding RNAs, have been found to be dysregulated in various cancers. However, the clinical application value of these circRNAs in digestive system cancers remains to be clarified. We aimed to comprehensively explore the potential role of circRNAs as diagnostic indicators in digestive system malignancies. METHODS: Relevant studies were systematically retrieved from PubMed, Web of Science and the Cochrane Library. The data that were required to complete 2 × 2 contingency tables were obtained from the included studies. Stratified analyses by cancer type, sample size and publication year were performed. RESULTS: Thirteen studies with 2,276 individuals were included in the meta-analysis. The pooled sensitivity and specificity of circRNAs in the diagnosis of digestive system malignancy were 0.72 [95% confidence interval (CI): 0.65-0.77] and 0.77 (95% CI: 0.72-0.81), respectively. The overall positive likelihood ratio was 3.09 (95% CI: 2.64-3.62), and the overall negative likelihood ratio was 0.37 (95% CI: 0.31-0.44). The pooled diagnostic odds ratio was 8.38 (95% CI: 6.86-10.25), and the overall area under the curve was 0.81 (95% CI: 0.77-0.84), indicating good discriminative ability of circRNAs as biomarkers for digestive system malignancy. CONCLUSION: circRNAs distinguish patients with digestive system cancer from controls with relatively high diagnostic accuracy. circRNAs may be used as potential biomarkers for the diagnosis of digestive system malignancy.

Bioinspired Photonic Barcodes with Graphene Oxide Encapsulation for Multiplexed MicroRNA Quantification.

Multiplexed microRNA (miRNA) quantification has a demonstrated value in clinical diagnosis. In this paper, novel mussel-inspired photonic crystal (PhC) barcodes with graphene oxide (GO) encapsulation for multiplexed miRNA detection are presented. Using the excellent adhesion capability of polydopamine, the dispersed GO particles can be immobilized on the surfaces of the PhC barcodes to form an additional functional layer. The GO-decorated PhC barcodes have constant characteristic reflection peaks because the GO immobilization process not only maintains their periodic microstructure but also enhances their stability and anti-incoherent light-scattering capability. The immobilized GO particles are shown to enable high-sensitivity miRNA screening on the surface of the PhC barcodes by integration with a hybridization chain reaction amplification strategy. Because the PhC barcodes have stable encoding reflection peaks, multiplexed low-abundance miRNA quantification can also be achieved rapidly, accurately, and reproducibly by employing different GO-decorated PhC barcodes. These features should make GO-encapsulated PhC barcodes ideal for many practical applications.

Application of microwave ablation in the emergent control of intraoperative life-threatening tumor hemorrhage during hepatic surgeries.

PURPOSE: This study was designed to evaluate the efficacy and safety of microwave ablation (MWA) in the treatment of intraoperative life-threatening tumour haemorrhage during hepatic surgeries. METHODS: Three cases of MWA application in the emergent control of life-threatening hepatic tumour haemorrhage were analysed and reported. RESULTS: Satisfactory hemostasis for hepatic tumour rupture was achieved by MWA in all three cases. No major complications, such as post-operative haemorrhage, bile duct injury, liver abscess, colon perforation, skin burns, tumour seeding or renal dysfunction, were identified. CONCLUSIONS: MWA may be a feasible, effective and simple strategy for the emergent control of intraoperative hepatic tumour bleeding. To the best of our knowledge, this study represents the first reported cases of this novel application of MWA.

Clinical value of octamer-binding transcription factor 4 as a prognostic marker in patients with digestive system cancers: A systematic review and meta-analysis.

BACKGROUND AND AIM: The role of octamer-binding transcription factor 4 (Oct4) has been implicated in the clinical prognosis of various kinds of digestive system cancers, but the results remain controversial. The purpose of this meta-analysis is to assess the potential role of Oct4 as a prognostic marker in digestive system tumors. METHODS: Relevant articles were retrieved from Pubmed, Web of Science, and Cochrane Library up to July 2016. The software Stata 12.0 was used to analyze the outcomes, including overall survival (OS), disease-free survival, recurrence-free survival, and clinicopathological characteristics. RESULTS: A total of 13 eligible studies with 1538 patients were included. Elevated Oct4 expression was significantly associated with poor OS (pooled hazard ratio [HR] = 2.183, 95% confidence interval [CI]: 1.824-2.612), disease-free survival (pooled HR = 1.973, 95% CI: 1.538-2.532), and recurrence-free survival (pooled HR = 2.209, 95% CI: 1.461-3.338) of digestive system malignancies. Subgroup analyses showed that cancer type, sample size, study quality, and laboratory detection method did not alter the significant prognostic value of Oct4. Additionally, Oct4 expression was found to be an independent predictive factor for OS (HR = 2.068, 95% CI: 1.633-2.619). No significant association was found between Oct4 and clinicopathological features of digestive system malignancies. CONCLUSION: This study provided evidence of Oct4 and/or its closely related homolog protein as a predictive factor for patients with digestive system cancers. More large-scale clinical studies on the prognostic value of Oct4 are warranted.

Comparative Profiling of Triple-Negative Breast Carcinomas Tissue Glycoproteome by Sequential Purification of Glycoproteins and Stable Isotope Labeling.

BACKGROUND: Women with triple negative breast cancers (TNBCs) have a poor prognosis due to lack of suitable targeted therapies. Changes in the protein glycosylation are increasingly being recognized as an important modification associated with cancer etiology. METHODS: In an attempt to identify TNBC biomarkers with greater diagnostic and prognostic capabilities, hydrazide- based chemistry method combined with LC-MS/MS were used to purify and identify N-linked glycopeptides or glycoproteins of tissues from TNBC patients. RESULTS: A total of 550 unique N-linked glycoproteins were identified, among these proteins, 72 unique N-linked glycoproteins were significantly regulated in tumor tissues, of which 56 proteins were upregulated and 16 proteins were downregulated. To assess the validity of the results, three selected proteins including Vascular endothelial growth factor receptor 1, Insulin receptor, Tissue factor pathway inhibitor were selected for western blot analysis, and these proteins were found as potential biomarkers of TNBC. The top three pathways of differentially expressed glycoproteins participated in were caveolar-mediated endocytosis signaling, agrin interactions at neuromuscular junction and LXR/RXR activation. CONCLUSION: This work provides potential glycoprotein markers to function as a novel tissue-based biomarker for TNBC.

Mitochondrial Proteomics Approach Reveals Voltage-Dependent Anion Channel 1 (VDAC1) as a Potential Biomarker of Gastric Cancer.

BACKGROUND/AIMS: Gastric cancer (GC) remains the second leading cause of cancer-related deaths in the world. Successful early cancer detection is hampered by lack of highly sensitive and specific biomarkers. Mitochondrial dysfunction contributes to an aggressive carcinogenic phenotype of many cancers. We hypothesized that changes in the mitochondrial proteome are required to support development of GC. METHODS: TMT method followed by mass spectrometry analysis was utilized to quantify alterations in protein abundance in mitochondria enriched between noncancer and gastric cancer tissues. RESULTS: Of a total data set that included 738 identified proteins, about 40.1% were found to be mitochondrial and associated proteins. Among them, 234 proteins were at least 1.5-fold up- or down-regulated in the gastric cancer compared with the adherent normal tissues. A number of markers (e.g. HSP70, HSP60, HSP90, leucine-rich pentatricopeptide repeat containing (LRPPRC), SOD2 and cathepsin B) were previously reported as biomarkers of GC. Additionally, several potential biomarkers participated in mitochondrial oxidative phosphorylation and active fatty acid oxidation were firstly identified differentially expressed in GC samples. Our findings also suggest that VDAC1 may be a novel biomarker for GC. CONCLUSION: The results show that subcellular proteomics of tumor tissue is feasible and a promising avenue for exploring oncogenesis.

Clinicopathological significance and prognostic value of the expression of the cancer stem cell marker CD133 in hepatocellular carcinoma: a meta-analysis.

To conduct a meta-analysis to assess the association between CD133 expression and clinicopathological significance and prognostic value in hepatocellular carcinoma patients. Studies were identified via an electronic comprehensive literature search through the Pubmed, Chinese CNKI, and Wanfang databases. This meta-analysis was performed using Stata statistical software version 12.0. The outcomes included various clinicopathological and survival parameters (P < 0.05 was consider to indicate a statistical significance). A total of 21 studies comprising 2592 patients were included in this meta-analysis. CD133 overexpression was significantly associated with a series of clinicopathological parameters, such as low tumor differentiation (pooled odds ratio (OR) = 2.26, 95% CI: 1.59-3.21, P < 0.00001), advanced tumor stage (pooled OR = 2.17, 95% CI: 1.70-2.77, P < 0.00001), vascular invasion (pooled OR = 2.06, 95% CI: 1.25-3.39, P = 0.005), and vascular thrombosis (pooled OR = 1.47, 95% CI: 1.08-1.99, P = 0.015). However, CD133 expression was not correlated with hepatitis, cirrhosis, α-fetoprotein level, tumor number, tumor size, encapsulation, or metastasis. Regarding survival outcome, CD133 overexpression was significantly correlated with poor overall survival (pooled hazard ratio (HR) = 2.01, 95% CI: 1.45-2.80, P = 0.00002) and poor disease-free survival (pooled HR = 1.82, 95% CI: 1.45-2.29, P < 0.00001). This meta-analysis indicated that CD133 overexpression is significantly associated with clinicopathological factors and poorer survival outcome.

Plasma membrane proteomic analysis of human Gastric Cancer tissues: revealing flotillin 1 as a marker for Gastric Cancer.

BACKGROUND: Gastric cancer remains the second leading cause of cancer-related deaths in the world. Successful early gastric cancer detection is hampered by lack of highly sensitive and specific biomarkers. Plasma membrane proteins participate and/or have a central role in the metastatic process of cancer cells and are potentially useful for cancer therapy due to easy accessibility of the targets. METHODS: In the present research, TMT method followed by mass spectrometry analysis was used to compare the relative expression levels of plasma membrane proteins between noncancer and gastric cancer tissues. RESULTS: Of a total data set that included 501 identified proteins, about 35% of the identified proteins were found to be plasma membrane and associated proteins. Among them, 82 proteins were at least 1.5-fold up- or down-regulated in gastric cancer compared with the adherent normal tissues. CONCLUSIONS: A number of markers (e.g. annexin A6, caveolin 1, epidermal growth factor receptor, integrin beta 4) were previously reported as biomarkers of GC. Additionally, several potential biomarkers participated in endocytosis pathway and integrin signaling pathways were firstly identified as differentially expressed proteins in GC samples. Our findings also supported the notion that flotillin 1 is a potential biomarker that could be exploited for molecular imaging-based detection of gastric cancer. Together, the results show that subcellular proteomics of tumor tissue is a feasible and promising avenue for exploring oncogenesis.

PNPLA3 polymorphisms (rs738409) and non-alcoholic fatty liver disease risk and related phenotypes: a meta-analysis.

BACKGROUND AND AIM: One single-nucleotide polymorphisms (SNPs) rs738409 in the patatin-like phospholipase domain-containing 3 gene (PNPLA3) has been implicated in susceptibility to non-alcoholic fatty liver disease (NAFLD) across different populations. One meta-analysis confirmed this association, but within it, only two Asian studies were included. This meta-analysis aimed to investigate the association in Asian population. METHODS: All eligible case-control studies were identified by searching through PubMed and Chinese language databases (CNKI and WanFang) up to July 1, 2014. Pooled estimates (odds ratio [OR] and standardized mean difference) were used to assess the strength of associations in fixed or random-effects models. RESULTS: A total of 12 studies with 4495 cases and 7431 controls were included. SNP rs738409 G allele was confirmed as a risk factor for NAFLD (G allele vs C allele: OR = 1.92, 95% confidence interval [95%CI]: 1.54-2.39). In addition, based on studies with certain clinical measurements data, G allele carriers were more likely to have higher level of serum alanine aminotransferase (ALT) (standard mean difference [SMD] = 7.03, 95% CI: 2.47-11.60), and higher fibrosis score (SMD = 0.39, 95% CI: 0.18-0.60). CONCLUSION: This study provided evidence of SNP rs738409 G allele as a strong risk factor of NAFLD susceptibility and higher level of serum ALT in Asian population.