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1.
Nucleic Acids Res ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31670377

RESUMO

Noncoding RNAs (ncRNAs) play crucial regulatory roles in a variety of biological circuits. To document regulatory interactions between ncRNAs and biomolecules, we previously created the NPInter database (http://bigdata.ibp.ac.cn/npinter). Since the last version of NPInter was issued, a rapidly growing number of studies have reported novel interactions and accumulated numerous high-throughput interactome data. We have therefore updated NPInter to its fourth edition in which are integrated 600 000 new experimentally identified ncRNA interactions. ncRNA-DNA interactions derived from ChIRP-seq data and circular RNA interactions have been included in the database. Additionally, disease associations were annotated to the interacting molecules. The database website has also been redesigned with a more user-friendly interface and several additional functional modules. Overall, NPInter v4.0 now provides more comprehensive data and services for researchers working on ncRNAs and their interactions with other biomolecules.

2.
Medicine (Baltimore) ; 98(39): e17198, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574828

RESUMO

BACKGROUND: The aim of our study was to assess the value of serum human epididymis protein 4 (HE4) to diagnose lung cancer and provide reliable scientific conclusions to guide clinical practice. METHODS: A systematic search of the PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature, and WANFANG databases was conducted to identify all studies examining serum HE4 in the diagnosis of lung cancer published up to June, 2017. The Quality Assessment of Diagnostic Accuracy Studies tool was used to evaluate the methodological quality of each trial. The meta-analysis was performed using STATA software and Review Manager 5.3. RESULTS: There were 21 studies involving 1883 cases and 1696 controls included in our meta-analysis. The pooled sensitivity and specificity of HE4 for diagnosing lung cancer were 0.73 (95% confidence interval [CI] 0.68-0.78) and 0.86 (95% CI 0.81-0.91), respectively. The positive likelihood ratio and negative likelihood ratio were 5.4 (95% CI 3.8-7.5) and 0.31 (95% CI 0.26-0.37), respectively. The diagnostic odds ratio was 17 (95% CI 12-26). The area under the curve of the summary receiver-operating characteristic curve was 0.86 (95% CI 0.83-0.89). Race, assay method, type of cancer, sample size, and publication date might be sources of heterogeneity in our meta-analysis. Subgroup analyses showed that the sensitivity in Caucasians was higher than that in Asians (0.81, 95% CI 0.71-0.91; and 0.71, 95% CI 0.66-0.77, respectively), but the specificity in Asians was better than that in Caucasians (0.87, 95% CI 0.81-0.92; and 0.85, 95% CI 0.73-0.97, respectively). The chemiluminescent microparticle immunoassay had the highest sensitivity, with 0.79 (95% CI 0.73-0.97), and the enzyme-linked immunosorbent assay had the highest specificity, with 0.87 (95% CI 0.79-0.94). HE4 had high diagnostic efficacy when screening for small cell lung cancer with the highest specificity (0.90, 95% CI 0.77-1.00). CONCLUSIONS: HE4 is a relatively promising and effective biomarker for the diagnosis of lung cancer. Furthermore, given the limitations of our study, additional large-scale and well-designed studies are needed in the future.


Assuntos
Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico , Proteínas/análise , Biomarcadores Tumorais/sangue , Humanos , Razão de Chances , Sensibilidade e Especificidade
3.
BMJ ; 367: l5460, 2019 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-31591158

RESUMO

OBJECTIVE: To compare the efficacy and safety of first line treatments for patients with advanced epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC). DESIGN: Systematic review and network meta-analysis. DATA SOURCES: PubMed, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and several international conference databases, from inception to 20 May 2019. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Published and unpublished randomised controlled trials comparing two or more treatments in the first line setting for patients with advanced EGFR mutated NSCLC were included in a bayesian network meta-analysis. Eligible studies reported at least one of the following clinical outcome measures: progression free survival, overall survival, objective response rate, and adverse events of grade 3 or higher. RESULTS: 18 eligible trials involved 4628 patients and 12 treatments: EGFR tyrosine kinase inhibitors (TKIs; osimertinib, dacomitinib, afatinib, erlotinib, gefitinib, and icotinib), pemetrexed based chemotherapy, pemetrexed free chemotherapy, and combination treatments (afatinib plus cetuximab, erlotinib plus bevacizumab, gefitinib plus pemetrexed based chemotherapy, and gefitinib plus pemetrexed). Consistent with gefitinib plus pemetrexed based chemotherapy (hazard ratio 0.95, 95% credible interval 0.72 to 1.24), osimertinib showed the most favourable progression free survival, with significant differences versus dacomitinib (0.74, 0.55 to 1.00), afatinib (0.52, 0.40 to 0.68), erlotinib (0.48, 0.40 to 0.57), gefitinib (0.44, 0.37 to 0.52), icotinib (0.39, 0.24 to 0.62), pemetrexed based chemotherapy (0.24, 0.17 to 0.33), pemetrexed free chemotherapy (0.16, 0.13 to 0.20), afatinib plus cetuximab (0.44, 0.28 to 0.71), and gefitinib plus pemetrexed (0.65, 0.46 to 0.92). Osimertinib and gefitinib plus pemetrexed based chemotherapy were also consistent (0.94, 0.66 to 1.35) in providing the best overall survival benefit. Combination treatments caused more toxicity in general, especially erlotinib plus bevacizumab, which caused the most adverse events of grade 3 or higher. Different toxicity spectrums were revealed for individual EGFR-TKIs. Subgroup analyses by the two most common EGFR mutation types indicated that osimertinib was associated with the best progression free survival in patients with the exon 19 deletion, and gefitinib plus pemetrexed based chemotherapy was associated with the best progression free survival in patients with the Leu858Arg mutation. CONCLUSIONS: These results indicate that osimertinib and gefitinib plus pemetrexed based chemotherapy were associated with the best progression free survival and overall survival benefits for patients with advanced EGFR mutated NSCLC, compared with other first line treatments. The treatments resulting in the best progression free survival for patients with the exon 19 deletion and Leu858Arg mutations were osimertinib and gefitinib plus pemetrexed based chemotherapy, respectively. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018111954.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Mutação , Biomarcadores Tumorais/genética , Receptores ErbB/genética , Humanos , Meta-Análise em Rede
4.
Sci Rep ; 9(1): 14452, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31595001

RESUMO

High-grade injuries of complete acromioclavicular (AC) joint disruption (types IV - VI) are typically treated surgically. Since the coracoclavicular (CC) ligament is most often used for stabilizing the AC joint, most reconstruction techniques to treat dislocation of this joint rely upon CC interval fixation. A TightRope system is usually used to augment the CC ligament to treat acute AC dislocations with arthroscopic assistance. The conventional arthroscopic technique employing one TightRope system is associated with some complications, including anterior subluxation of the clavicle and clavicular bony avulsion as a consequence of rotational movements. As an alternative, two TightRope systems can be used to anatomically reconstruct the CC ligament to avoid these complications. We present a new CC guider with which the surgeon can replicate the native CC ligament complex orientation using two TightRope systems via two minimally invasive incisions without arthroscopic assistance. This procedure relies upon the accommodation and stable placement of the clavicle and coracoid bone tunnels for the two TightRope systems in place of the trapezoid and conoid of the CC ligament. We retrospectively reviewed the outcomes for 16 patients with acute dislocation of the AC joint that had been treated by a single surgeon using a double-button fixation system. An independent reviewer conducted functional testing of these patients, including the use of Disability of Arm, Shoulder and Hand (DASH), Constant and visual analog scale (VAS) scores. Standard radiographs were used for assessing the CC distance for the impacted shoulder relative to that of the unaffected contralateral shoulderThe new CC guider leads to an excellent cosmetic result. Our clinical results show that this technique can be easily performed and is similarly invasive to other current arthroscopic techniques.

5.
Sensors (Basel) ; 19(20)2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31658617

RESUMO

Hospitals need to invest a lot of manpower to manually input the contents of medical invoices (nearly 300,000,000 medical invoices a year) into the medical system. In order to help the hospital save money and stabilize work efficiency, this paper designed a system to complete the complicated work using a Gaussian blur and smoothing-convolutional neural network combined with a recurrent neural network (GBS-CR) method. Gaussian blur and smoothing (GBS) is a novel preprocessing method that can fix the breakpoint font in medical invoices. The combination of convolutional neural network (CNN) and recurrent neural network (RNN) was used to raise the recognition rate of the breakpoint font in medical invoices. RNN was designed to be the semantic revision module. In the aspect of image preprocessing, Gaussian blur and smoothing were used to fix the breakpoint font. In the period of making the self-built dataset, a certain proportion of the breakpoint font (the font of breakpoint is 3, the original font is 7) was added, in this paper, so as to optimize the Alexnet-Adam-CNN (AA-CNN) model, which is more suitable for the recognition of the breakpoint font than the traditional CNN model. In terms of the identification methods, we not only adopted the optimized AA-CNN for identification, but also combined RNN to carry out the semantic revisions of the identified results of CNN, meanwhile further improving the recognition rate of the medical invoices. The experimental results show that compared with the state-of-art invoice recognition method, the method presented in this paper has an average increase of 10 to 15 percentage points in recognition rate.

7.
J Cell Physiol ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31637718

RESUMO

Colorectal neoplasms are a type of malignant digestive system tumor that has become the third-highest morbidity tumor in China and the fourth leading cause of cancer-related death worldwide. The role of the gastrointestinal (GI) microbiome in bile acid metabolism, inflammation, and insulin resistance and its strong correlation with the occurrence and development of colorectal neoplasms have gradually led to it becoming a target area of tumor research. Fibroblast growth factor (FGF) 19 is a hormone that is secreted in mainly the ileum and can regulate bile acid biosynthesis, improve inflammation, and regulate insulin resistance. The relationship of the GI microbiome, FGF19 and its carcinogenic activities in colorectal neoplasms enticed us to search for potential targets and research ideas for the clinical diagnosis and treatment of colorectal neoplasms.

8.
ACS Appl Mater Interfaces ; 11(43): 39574-39585, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31589019

RESUMO

In the past few decades, intracellular calcium overload has been shown to induce cell death through multiple signaling pathways. In this study, we used BAPTA-AM, a well-known membrane-permeable Ca2+ chelator, to prevent cell injury by allaying the intracellular calcium overload. We explored the clinical potentials of BAPTA-AM-loaded liposome (BAL) in the treatment of the acute liver failure (ALF) mouse model, which is characterized by severe hepatic necrosis and apoptosis. We discovered that BAL can significantly inhibit D-GalN-induced LO2 cell damage as it increased cell viability by 60% and downregulated the LPS-stimulated inflammatory response in RAW 264.7 macrophages by reversing the morphological change and modulating TNF-α and NF-κB expressions. Through systemic administration, BAL can rapidly accumulate in damaged liver tissue and exhibit excellent treatment effects on the D-GalN/LPS-induced ALF mouse model, including elevation of the survival rate (from 10 to 80%), recovery of normal liver indexes and liver health indicators, improvement of liver blood microcirculation (increased the blood flow volume by 80% and flow rate by 60%), and blood coagulation. The underlying hepatoprotective effect of BAL is presumably based on the antinecrosis and antiapoptosis abilities attributed to its inhibition on oxidative stress, restriction on TNF-α receptor, and mitochondria-mediated apoptotic pathway by effectively clearing the overloaded intercellular calcium. BAL holds great potential as a new therapeutic strategy for ALF treatment, and its prominent cell rescue ability provides ample opportunities for the treatment of many other diseases that are characterized by rapid and massive cell damage.

9.
Int Rev Immunol ; : 1-23, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31662000

RESUMO

Infectious diseases are a major challenge for the poultry industry that causes widespread production losses. Thus, management and control of poultry health and diseases are essential for the viability of the industry. Toll-like receptors are best characterized as membrane-bound receptors that perform a central role in immune homeostasis and disease resistance by recognition of pathogen-associated molecular patterns. In response to pathogen recognition, TLRs initiate both innate and adaptive immune responses which may help to develop immunomodulatory therapeutics for TLR associated diseases. Vaccination produces specific immunity in the animal's body towards pathogens. However, due to certain disadvantages of vaccines, (inactivation of attenuated pathogens into the virulent strains and weak immunogenicity of inactivated vaccines) there is a crucial need to develop the safe and effective therapeutic intervention. TLR ligands have been classified as a potential adjuvant against the infectious diseases in farm animals. TLR adjuvants induce both specific and nonspecific immune responses in chickens to combat several bacterial, viral and parasitic diseases. Therefore, the aim of this review was to explore the chicken TLR4 and their role in immune responses and disease resistance to develop disease resistance poultry breeds in future.

11.
FEBS Lett ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31665817

RESUMO

Pullulanases are well-known debranching enzymes hydrolyzing α-1,6-glycosidic linkages. To date, engineering of pullulanase is mainly focused on catalytic pocket or domain tailoring based on structure/sequence information. Saturation mutagenesis-involved directed evolution is, however, limited by the low number of mutational sites compatible with combinatorial libraries of feasible size. Using Bacillus naganoensis pullulanase as a target protein, here we introduce the "evolutionary coupling saturation mutagenesis" (ECSM) approach: residue pair co-variances are calculated to identify residues for saturation mutagenesis, focusing directed evolution on residue pairs playing important roles in natural evolution. Evolutionary coupling (EC) analysis identified seven residue pairs as evolutionary mutational hotspots. Subsequent saturation mutagenesis yielded variants with enhanced catalytic activity. The functional pairs apparently represent distant sites affecting enzyme activity.

12.
Nucleic Acids Res ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31599330

RESUMO

The leaf senescence database (LSD) is a comprehensive resource of senescence-associated genes (SAGs) and their corresponding mutants. Through manual curation and extensive annotation, we updated the LSD to a new version LSD 3.0, which contains 5853 genes and 617 mutants from 68 species. To provide sustainable and reliable services for the plant research community, LSD 3.0 (https://bigd.big.ac.cn/lsd/) has been moved to and maintained by the National Genomics Data Center at Beijing Institute of Genomics, Chinese Academy of Sciences. In the current release, we added some new features: (i) Transcriptome data of leaf senescence in poplar were integrated; (ii) Leaf senescence-associated transcriptome data information in Arabidopsis, rice and soybean were included; (iii) Senescence-differentially expressed small RNAs (Sen-smRNA) in Arabidopsis were identified; (iv) Interaction pairs between Sen-smRNAs and senescence-associated transcription factors (Sen-TF) were established; (v) Senescence phenotypes of 90 natural accessions (ecotypes) and 42 images of ecotypes in Arabidopsis were incorporated; (vi) Mutant seed information of SAGs in rice obtained from Kitbase was integrated; (vii) New options of search engines for ecotypes and transcriptome data were implemented. Together, the updated database bears great utility to continue to provide users with useful resources for studies of leaf senescence.

13.
Org Lett ; 21(18): 7635-7638, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31507178

RESUMO

A diphenyl-diselenide-mediated Claisen-type rearrangement/cyclization of propargylic aryl ethers under metal-free conditions is developed, affording various naphthofuran-2-carboxaldehydes in moderate to excellent yield. The broad substrate scope and excellent functional group compatibility suggest that it can be a straightforward and powerful method to access naphthofuran-2-carboxaldehydes in a highly regioselective manner. Moreover, this reaction can be scaled up to the gram scale.

14.
Acta Biochim Biophys Sin (Shanghai) ; 51(10): 1008-1015, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31559412

RESUMO

Tumor necrosis factor α-induced protein 8-like-1 (TIPE1) functions as an activator or a repressor in a tumor cell type-specific manner. However, the role of TIPE1 in breast cancer, especially regarding metastasis, is unknown. In this study, we aimed to investigate the TIPE1 expression in breast cancer tissues, the biological functions, and the underlying mechanisms of TIPE1 regarding the metastatic properties of breast cancer cells. The results of immunohistochemical staining and western blot analysis indicated that TIPE1 expression was associated with tumor size and lymph node metastasis, and the expression of TIPE1 was downregulated in the tissues of patients with lymph node metastasis. Transwell and wound healing assay results showed that TIPE1 inhibited the invasive and migratory capacities of breast cancer cells. Moreover, the epithelial-mesenchymal transition (EMT) was suppressed in TIPE1-overexpressing cells, as demonstrated by western blot analysis. In addition, western blot analysis also showed that TIPE1 reduced the expression levels of MMP2 and MMP9 and decreased the phosphorylation level of ERK. These results suggested that TIPE1 might suppress the invasion and migration of breast cancer cells and inhibit EMT primarily via the ERK signaling pathway. Our findings revealed the anti-tumor metastasis role of TIPE1 in breast cancer and TIPE1 might be a new candidate prognostic indicator and a potential molecular target for the treatment of breast cancer.

15.
Arch Oral Biol ; 108: 104509, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31494437

RESUMO

OBJECTIVE: To describe and compare cytokines levels in clinically healthy sites of dental implants and natural teeth. MATERIALS AND METHODS: A total of 90 dental implants in 71 periodontal healthy patients with function time of less than 6 months after the completion of the implant prosthesis were included in this study. PICF (peri-implant crevicular fluid) and GCF (gingival crevicular fluid) samples were collected from implants and the contralateral natural teeth. In addition, we performed a dynamic collection of crevicular fluid from 18 dental implants and their contralateral natural teeth at four time nodes (first day, first week, first month, third month). The profiles of 45 common cytokines in PICF and GCF were analyzed by Luminex multiplex assays. RESULTS: The total volume of PICF was significantly higher when compared to the volume of GCF (p < 0.01). In contrast, the concentrations of IL-18, IL-2, IL-23, IL-21, IL-1α, IL-12p70, VEGF-A, HGF, FGF-2, BDNF, PlGF-1, MIP-1ß, TNF-α, and IFN-γ in PICF were significantly lower than those in GCF (p < 0.05). In the longitudinal component of the study, the cytokines found in PICF underwent a brief wave of expression in the 3-month period, with the smallest gap difference of cytokine expression between the PICF and the GCF being at first month. CONCLUSIONS: This study observed that the levels of 14 cytokine profiles were lower in PICF than in GCF. Within the implants load for one month, the levels of above differential cytokines in PICF increased and gradually approached the cytokine profiles in GCF.

16.
Chem Phys Lipids ; : 104832, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31560875

RESUMO

Bone diseases are notoriously difficult diseases to treat due to the comparatively low blood flows in bone tissue. Therefore, targeting delivery of drugs to bone may not only enhance the treatment efficacy, but also reduce the quantity of drug administered. In order to increase the distribution of paclitaxel (PTX) in bone, in this study, a series of novel dendritic aspartic acid derivatives were designed and synthesized as liposome ligands to deliver PTX to bone effectively. The liposomes were prepared by thin film hydration method and its particle size, zeta potential, encapsulation efficiency, release profile, stability, hemolysis were also characterized. All the aspartic acid-coated liposomes showed more than 60% binding rates to hydroxyapatite (HAP), especially the PTX-Asp8-Lip exhibited dramatic binding rates (> 97%) after 24 h. Moreover, the bone-targeting study in vivo indicated that all liposomes could improve the accumulation of PTX in bone, among which, the PTX-Asp8-Lip showed the best affinity due to the increase of aspartic acid residues exposed on the liposome surface. These results provided a novel and effective entry to the development of bone-targeting drugs.

17.
J Alzheimers Dis ; 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31561366

RESUMO

Most of the loci identified by genome-wide association studies (GWAS) for late-onset Alzheimer's disease (LOAD) are in strong linkage disequilibrium (LD) with nearby variants all of which could be the actual functional variants, often in non-protein-coding regions and implicating underlying gene regulatory mechanisms. We set out to characterize the causal variants, regulatory mechanisms, tissue contexts, and target genes underlying these associations. We applied our INFERNO algorithm to the top 19 non-APOE loci from the IGAP GWAS study. INFERNO annotated all LD-expanded variants at each locus with tissue-specific regulatory activity. Bayesian co-localization analysis of summary statistics and eQTL data was performed to identify tissue-specific target genes. INFERNO identified enhancer dysregulation in all 19 tag regions analyzed, significant enrichments of enhancer overlaps in the immune-related blood category, and co-localized eQTL signals overlapping enhancers from the matching tissue class in ten regions (ABCA7, BIN1, CASS4, CD2AP, CD33, CELF1, CLU, EPHA1, FERMT2, ZCWPW1). In several cases, we identified dysregulation of long noncoding RNA (lncRNA) transcripts and applied the lncRNA target identification algorithm from INFERNO to characterize their downstream biological effects. We also validated the allele-specific effects of several variants on enhancer function using luciferase expression assays. By integrating functional genomics with GWAS signals, our analysis yielded insights into the regulatory mechanisms, tissue contexts, genes, and biological processes affected by noncoding genetic variation associated with LOAD risk.

18.
Int J Med Sci ; 16(8): 1078-1088, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31523169

RESUMO

Yunnan Baiyao (YB) as a kind of famous Chinese herbal medicine, possessed hemostatic, invigorating the circulation of blood, and anti-inflammatory effects. Identifying strategies to protect patients at risk for hospital-acquired pressure ulcers (HAPU) is essential. Herein, our results showed that YB treatment can effectively reduce the acne wound area and improve efficacy in a comparative study of 60 cases HAPU patients with S. aureus positive of acne wound pathogens. Furthermore, YB inhibited HIa expression and suppressed accessory gene regulator (agr) system controlled by regulatory RNA II and RNA III molecule using pALC1740, pALC1742 and pALC1743 S. aureus strain linked to gfpuvr reporter gene. Moreover, YB downregulated cao mRNA expression and inhibited coagulase activity by RT-PCR, slide and tube coagulase test. Additionally, YB downregulated seb, sec, sed, and tsst-1 mRNA expression to suppress enterotoxin and tsst-1 secretion and adhesion function related genes sarA, icaA, and cidA mRNA expression. Taken together, the data suggest that YB may reduce HAPU via suppressing virulence gene expression and biofilm formation of S. aureus.

19.
Front Immunol ; 10: 2064, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31543879

RESUMO

T cells recognize antigens as peptides bound to major histocompatibility complex (MHC) proteins through T cell receptors (TCRs) on their surface. To recognize a wide range of pathogens, each individual possesses a substantial number of TCRs with an extremely high degree of variability. It remains controversial whether germline-encoded TCR repertoire is shaped by MHC polymorphism and, if so, what is the preference between MHC genetic variants and TCR V gene compatibility. To investigate the "net" genetic association between MHC variations and TRBV genes, we applied quantitative trait locus (QTL) mapping to test the associations between MHC polymorphism and TCR ß chain V (TRBV) genes usage using umbilical cord blood (UCB) samples of 201 Chinese newborns. We found TRBV gene and MHC loci that are predisposed to interact with one another differ from previous conclusions. The majority of MHC amino acid residues associated with the TRBV gene usage show spatial proximities in known structures of TCR-pMHC complexes. These results show for the first time that MHC variants bias TRBV gene usage in UCB of Chinese ancestry and indicate that germline-encoded contacts influence TCR-MHC interactions in intact T cell repertoires.

20.
J Cell Physiol ; 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31556110

RESUMO

Studies have shown that microRNAs (miRNAs) play a vital role in tumor progression and patients' prognosis. Therefore, we aimed to construct a miRNA model for forecasting the survival of hepatocellular carcinoma (HCC) patients. The gene expression data of 433 patients with HCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus public databases were remined by survival analysis and receptor manipulation characteristic curve (ROC). A prognostic model including six miRNAs (hsa-mir-26a-1-3p, hsa-mir-188-5p, hsa-mir-212-5p, hsa-mir-149-5p, hsa-mir-105-5p, and hsa-mir-132-5p) were constructed in the training dataset (TCGA, n = 333). HCC patients were stratified into a high-risk group and a low-risk group with significantly different survival (median: 2.75 vs. 8.93 years, log-rank test p < .001). Then we proved its performance of stratification in another independent dataset (GSE116182, median: 2.55 vs 6.96 years, log-rank test p = .008). Cox regression analysis showed that the prognostic model was an independent prognostic indicator for HCC patients. Then time-dependent ROC analyses were performed to test the prognostic ability of the model with that of TNM staging, we found the model had a better performance, especially at 5 years (AUC = 0.76). Functional prediction showed that the genes targeted by the six prognostic miRNAs in the prognostic model were highly expressed in the P53-related pathway. In conclusion, we constructed a prognostic miRNA model that could indicate the survival of HCC patients.

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