Candidate Prognostic Biomarker Research Articles

Discovery of Prognostic Markers for Early-Stage High-Grade Serous Ovarian Cancer by Maldi-Imaging.

With regard to relapse and survival, early-stage high-grade serous ovarian (HGSOC) patients comprise a heterogeneous group and there is no clear consensus on first-line treatment. Currently, no prognostic markers are available for risk assessment by standard targeted immunohistochemistry and novel approaches are urgently required. Here, we applied MALDI-imaging mass spectrometry (MALDI-IMS), a new method to identify distinct mass profiles including protein signatures on paraffin-embedded tissue sections. In search of prognostic biomarker candidates, we compared proteomic profiles of primary tumor sections from early-stage HGSOC patients with either recurrent (RD) or non-recurrent disease (N = 4; each group) as a proof of concept study. In total, MALDI-IMS analysis resulted in 7537 spectra from the malignant tumor areas. Using receiver operating characteristic (ROC) analysis, 151 peptides were able to discriminate between patients with RD and non-RD (AUC > 0.6 or < 0.4; p < 0.01), and 13 of them could be annotated to proteins. Strongest expression levels of specific peptides linked to Keratin type1 and Collagen alpha-2(I) were observed and associated with poor prognosis (AUC > 0.7). These results confirm that in using IMS, we could identify new candidates to predict clinical outcome and treatment extent for patients with early-stage HGSOC.

Cognitive decline in Parkinson's disease is associated with reduced complexity of EEG at baseline.

Parkinson’s disease is a neurodegenerative disorder requiring motor signs for diagnosis, but showing more widespread pathological alterations from its beginning. Compared to age-matched healthy individuals, patients with Parkinson’s disease bear a 6-fold lifetime risk of dementia. For individualized counselling and treatment, prognostic biomarkers for assessing future cognitive deterioration in early stages of Parkinson’s disease are needed. In a case–control study, 42 cognitively normal patients with Parkinson’s disease were compared with 24 healthy control participants matched for age, sex and education. Tsallis entropy and band power of the δ, θ, α, β and γ-band were evaluated in baseline EEG at eyes-open and eyes-closed condition. As the θ-band showed the most pronounced differences between Parkinson’s disease and healthy control groups, further analysis focussed on this band. Tsallis entropy was then compared across groups with 16 psychological test scores at baseline and follow-ups at 6 months and 3 years. In group comparison, patients with Parkinson’s disease showed lower Tsallis entropy than healthy control participants. Cognitive deterioration at 3 years was correlated with Tsallis entropy in the eyes-open condition (P < 0.00079), whereas correlation at 6 months was not yet significant. Tsallis entropy measured in the eyes-closed condition did not correlate with cognitive outcome. In conclusion, the lower the EEG entropy levels at baseline in the eyes-open condition, the higher the probability of cognitive decline over 3 years. This makes Tsallis entropy a candidate prognostic biomarker for dementia in Parkinson’s disease. The ability of the cortex to execute complex functions underlies cognitive health, whereas cognitive decline might clinically appear when compensatory capacity is exhausted.

Plasma Extracellular Vesicle-Derived TIMP-1 mRNA as a Prognostic Biomarker in Clear Cell Renal Cell Carcinoma: A Pilot Study.

The tumor microenvironment has gained a lot of attention from the scientific community since it has a proven impact in the development of tumor progression and metastasis. Extracellular vesicles (EVs) are now considered one of the key players of tumor microenvironment modulation. Clear cell renal cell carcinoma (ccRCC) is the most lethal urological neoplasia and presents a high metastatic potential, which reinforces the need for the development of more effective predictive biomarkers. Our goal was to evaluate the applicability of EV-derived matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) as prognostic biomarkers for ccRCC. To do so, we studied the plasma EV content of 32 patients with localized ccRCC and 29 patients with metastatic ccRCC. We observed that patients with localized disease and tumors larger than 7 cm presented higher levels of plasma EV-derived TIMP-1 mRNA when compared with patients presenting smaller tumors (p = 0.020). Moreover, patients with metastatic disease presented higher levels of EV-derived TIMP-1 mRNA when compared with patients with localized disease (p = 0.002) and when we stratified those patients in high and low levels of TIMP-1 EV-derived mRNA, the ones presenting higher levels had a lower overall survival (p = 0.030). EV-derived TIMP-1 mRNA may be a good prognostic biomarker candidate for ccRCC.

Multimodal Evoked Potentials as Candidate Prognostic and Response Biomarkers in Clinical Trials of Multiple Sclerosis.

Evoked potentials (EPs) measure quantitatively and objectively the alterations of central signal propagation in multiple sclerosis and have long been used for diagnosis. More recently, their utility for prognosis has been demonstrated in several studies, summarizing multiple EP modalities in a single score. In particular, visual, somatosensory, and motor EPs are useful because of their sensitivity to pathology in the frequently affected optic nerve, somatosensory tract, and pyramidal system. Quantitative EP scores show higher sensitivity to change than clinical assessment and may be used to monitor disease progression. Visual EP and the visual system have served as a model to study remyelinating therapies in the setting of acute and chronic optic neuritis. This review presents rationale and evidence for using multimodal EP as prognostic and response biomarkers in clinical trials, targeting remyelination or halting disease progression in multiple sclerosis.

Label-free proteomics reveals serum proteins whose levels differ between pancreatic ductal adenocarcinoma patients with short or long survival.

Pancreatic ductal adenocarcinoma is the most common and aggressive type of pancreatic cancer, with a 5-year survival rate that is less than 10%. New biomarkers to aid in predicting the prognosis of pancreatic ductal adenocarcinoma patients are needed. Previous proteomic studies have to a great extent focused on finding proteins of value for the diagnosis of pancreatic ductal adenocarcinoma. There is a lack of studies that have profiled the serum or plasma proteome in order to discover candidates for new prognostic biomarkers. In this study, we have used ultra-performance liquid chromatography-ultra-definition mass spectrometry to analyze the serum samples of 21 pancreatic ductal adenocarcinoma patients with short or long survival. Statistical analysis discovered 31 proteins whose expression differed significantly between pancreatic ductal adenocarcinoma patients with short or long survival. Pathway analysis discovered multiple canonical pathways enriched in this data set, with several pathways having roles in inflammation and lipid metabolism. The serum proteins identified here, which include complement components and several enzymes, could be of value as candidates for new noninvasive prognostic markers.

Overexpression of miR‑518b in non‑small cell lung cancer serves as a biomarker and facilitates tumor cell proliferation, migration and invasion

Several microRNAs (miRNA/miR) have been reported to serve critical roles in tumorigenesis. The present study aimed to investigate miR-518b expression in non-small cell lung cancer (NSCLC), and determine its clinical significance and biological function in this malignancy. Reverse transcription-quantitative PCR was performed to assess miR-518b expression in NSCLC. The diagnostic value of miR-518b was determined via a receiver operating characteristic curve, while its prognostic value was assessed using the Kaplan-Meier method. Gain- and loss-of-function experiments were performed to determine the functional role of miR-518b in NSCLC progression. The results demonstrated that miR-518b expression was upregulated in NSCLC serum, tissues and cell lines compared with the corresponding normal controls. Furthermore, high miR-518b expression was significantly associated with larger tumor size, lymph node metastasis and advanced TNM stage, as well as poor overall survival in patients with NSCLC. Serum miR-518b expression was identified as a candidate diagnostic biomarker for NSCLC, with sensitivity of 88.1% and specificity of 81.7%. Furthermore, the cell experiments indicated that NSCLC cell proliferation, migration and invasion were enhanced following overexpression of miR-518b; however, these effects were reversed following miR-518b knockdown. Taken together, the results of the present study suggest that elevated miR-518b expression in NSCLC serves a potential oncogenic role by facilitating tumor cell proliferation, migration and invasion, and thus may serve as a candidate diagnostic and prognostic biomarker.

Prognostic biomarker candidates of neoadjuvant chemotherapy for luminal B-positive locally advanced breast cancer.

e12638 Background: In the last decade, the treatment approach for locally advanced breast cancer (BC) patients has partly shifted from adjuvant treatment to neoadjuvant treatment. Systemic neoadjuvant treatment can downstage the tumor for less extensive surgery and improve cosmetic outcomes. Differential subtypes of BC responded unevenly to neoadjuvant chemotherapy. Luminal B type with the relatively higher prevalence (40% in all 4 subtypes) had better therapeutic effect to neoadjuvant treatment than luminal A type, but worse than HER2-positive patients. Methods: We enrolled 87 BC patients for genotyping with multiple cancer-related genes. Among them, 17 patients were luminal A, 21 were HER2-negative luminal B, 23 were HER2-positive luminal B, 17 were HER2-positive and 9 were triple-negative. According to the RECIST, the patients were divided into 1-4 and 5 grades. Fisher test was used to analyze the difference of SNV and CNV between the two primary tumors, as well as TMB difference between post-neoadjuvant chemotherapy and past-neoadjuvant chemotherapy. Results: Base mutations in all patients showed discrepant preference between 1-4 grades and 5 grade groups, G-to-A in 1-4 grades, while A-to-G, A-to-T and G-to-T in 5 grade. In luminal B group (combine liminal B-negative and luminal B-positive groups), FLT4 gene mutation occurred more frequent in 5 grade than 1-4 grades (4/16 vs 0/28, P = 0.01). CNV analysis in NFKBIA and ZNF217 distinguished the two therapeutic efficiency groups in luminal B-positive group. The amplification of NFKBIA and ZNF217 was higher in 1-4 grades than 5 grade (8/14 vs 1/9, P = 0.036; 9/14 vs 1/9, P = 0.017). TMB difference between post and past neoadjuvant chemotherapy in luminal B-positive group was also significant in 5 grade (4.36 vs 1.99, P = 0.002). Conclusions: NFKBIA and ZNF217 amplification notably differentiated the 1-4 grades and 5 grade groups in luminal B-positive patients, suggesting the potential prognostic biomarkers of neoadjuvant chemotherapy in this locally advanced breast cancer subtype, which would be improved by further large-scale cohort study. The differences of TMB and FLT4 gene mutation were also found between the two therapeutic efficiency groups.

Dysregulation of miR-3607 predicts prognosis of hepatocellular carcinoma and regulates tumor cell proliferation, migration and invasion

BackgroundHepatocellular carcinoma (HCC) is one of the most common global malignancies with increasing morbidity and mortality. The purpose of this study was to investigate the expression levels and prognostic value of microRNA-3607 (miR-3607) in patients with HCC.MethodsThe expression of miR-3607 was estimated by quantitative real-time RT-PCR. Survival analysis using the Kaplan-Meier method and Cox regression analysis was conducted to evaluate the prognostic value of miR-3607. The functional role of miR-3607 in HCC progression was further assessed using gain- and loss-of-function experiments. Bioinformatics analysis and a dual-luciferase reporter assay were used to explore the direct targets of miR-3607.ResultsmiR-3607 expression was found to be significantly decreased in HCC tissues and cells compared with the matched tissues and cells (P < 0.001). The decreased expression of miR-3607 was associated with the patients’ tumor size and TNM stage (all P < 0.05). According to the survival curves, patients with low miR-3607 expression had poorer overall survival than those with high levels (log-rank P = 0.012). Moreover, the Cox analysis results indicated that miR-3607 expression was an independent prognostic factor for HCC. The results of cell experiments revealed that the overexpression of miR-3607 in HCC cells led to the inhibited cell proliferation, migration, and invasion. TGFBR1 was identified as a direct target of miR-3607.ConclusionThe data of this study indicated that the decreased expression of miR-3607 in HCC predicts poor prognosis and the overexpression of miR-3607 in HCC cells can suppress the tumor progression by targeting TGFBR1. This study provides a novel insight into the prognosis and treatment of HCC, and miR-3607 serves as a candidate prognostic biomarker and therapeutic target of HCC.

SIRT7 Is a Prognostic Biomarker Associated With Immune Infiltration in Luminal Breast Cancer.

Background: Sirtuin 7 (SIRT7), a protein-coding gene whose abnormal expression and function are associated with carcinogenesis. However, the prognosis of SIRT7 in different breast cancer subtypes and its correlation with tumor-infiltrating lymphocytes remain unclear.Methods: The expression and survival data of SIRT7 in patients with breast cancer were analyzed using Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interaction Analysis (GEPIA), The Human Protein Atlas (HPA), UALCAN, Breast Cancer Gene-Expression Miner (BC-GenExMiner), and Kaplan-Meier plotter databases. Also, the expression correlations between SIRT7 and immune infiltration gene markers were analyzed using TIMER and further verified the results using immunohistochemistry.Results: SIRT7 exhibited higher expression levels in breast cancer tissues than the adjacent normal tissues. SIRT7 expression was significantly correlated with sample type, subclass, cancer stage, menopause status, age, nodal status, estrogen receptor (ER), progesterone receptor (PR), and triple-negative status. High SIRT7 expression was associated with poor prognosis in breast cancer-luminal A [overall survival (OS): hazard ratio (HR) = 1.54, p = 1.70e-02; distant metastasis-free survival (DMFS): HR = 1.56, p = 2.60e-03]. Moreover, the expression of SIRT7 was positively correlated with the expression of IRF5 (M1 macrophages marker, r = 0.165, p = 1.13e-04) and PD1 (T cell exhaustion marker, r = 0.134, p = 1.74e-03). These results suggested that the expression of SIRT7 was related to M1 macrophages and T cell exhaustion infiltration in breast cancer-luminal.Conclusions: These findings demonstrate that the high expression of SIRT7 indicates poor prognosis in breast cancer as well as increased immune infiltration levels of M1 macrophages and T cell exhaustion in breast cancer-luminal. Thus, SIRT7 may serve as a candidate prognostic biomarker for determining prognosis associated with immune infiltration in breast cancer-luminal.

Characterization of KIF20A as a prognostic biomarker and therapeutic target for different subtypes of breast cancer.

The aim of the present study was to identify novel prognostic biomarkers and therapeutic targets for breast cancer; thus, genes that are frequently overexpressed in several types of breast cancer were screened. Kinesin family member20A (KIF20A) was identified as a candidate molecule during this process. Immunohistochemical staining performed using tissue microarrays from 257samples of different breast cancer subtypes revealed that KIF20A was expressed in195 (75.9%) of these samples, whereas it was seldom expressed in normal breast tissue. KIF20A protein was expressed in all types of breast cancer observed. However, it was more frequently expressed in human epidermal growth factor receptor2 (HER2)‑positive and triple‑negative breast cancer than in the luminal type. Moreover, KIF20A expression was significantly associated with the poor prognosis of patients with breast cancer. A multivariate analysis indicated that KIF20A expression was an independent prognostic factor for patients with breast cancer. The suppression of endogenous KIF20A expression using small interfering ribonucleic acids or via treatment with paprotrain, a selective inhibitor of KIF20A, significantly inhibited breast cancer cell growth through cell cycle arrest at the G2/M phase and subsequent mitotic cell death. These results suggest that KIF20A is a candidate prognostic biomarker and therapeutic target for different types of breast cancer.

MicroRNA-374b-5p Functions as a Tumor Suppressor in Non-Small Cell Lung Cancer by Targeting FOXP1 and Predicts Prognosis of Cancer Patients.

BackgroundLung cancer remains the most frequent malignancy worldwide with increasing morbidity and mortality. This study aimed to assess the expression of microRNA-374b-5p (miR-374b-5p) in tissues and cell lines of non-small cell lung cancer (NSCLC) and to evaluate the prognostic value of miR-374b-5p as well as its biological function in tumor progression.Materials and MethodsExpression of miR-374b-5p in NSCLC patients and cells was estimated using quantitative real-time PCR. The prognostic value of miR-374b-5p was evaluated using Kaplan–Meier method and Cox regression analysis. Gain-of-function and loss-of-function cell experiments were performed to examine the effects of miR-374b-5p on NSCLC cell proliferation, migration and invasion. A luciferase activity assay was used to confirm the target gene of miR-374b-5p.ResultsmiR-374b-5p expression levels were decreased in tumorous tissues and cell lines compared with the normal tissues or cells (P < 0.05). The expression of miR-374b-5p was associated with the patients’ tumor size, lymph node metastasis and TNM stage (all P < 0.05). Patients with low miR-374b-5p expression have a shorter survival time (log-rank P = 0.001), and the downregulated expression of miR-374b-5p was determined to be an independent prognostic indicator of NSCLC. In NSCLC cells, the overexpression of miR-374b-5p could inhibit NSCLC cell proliferation, migration and invasion and could directly target FOXP1.ConclusionThis study found that the decreased miR-374b-5p predicts poor prognosis of NSCLC, and the upregulation of miR-374b-5p can inhibit NSCLC cell proliferation, migration and invasion. The data obtained from this study provide a novel candidate prognostic biomarker and a potential therapeutic target for NSCLC.

The SLC Family Are Candidate Diagnostic and Prognostic Biomarkers in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common lethal subtype of renal cancer, and changes in tumor metabolism play a key role in its development. Solute carriers (SLCs) are important in the transport of small molecules in humans, and defects in SLC transporters can lead to serious diseases. The expression patterns and prognostic values of SLC family transporters in the development of ccRCC are still unclear. The current study analyzed the expression levels of SLC family members and their correlation with prognosis in ccRCC patients with data from Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), The Cancer Genome Atlas (TCGA), cBioPortal, the Human Protein Atlas (HPA), the International Cancer Genome Consortium (ICGC), and the Gene Expression Omnibus (GEO). We found that the mRNA expression levels of SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were significantly lower in ccRCC tissues than in normal tissues and the protein expression levels of SLC22A6, SLC22A7, SLC22A13, and SLC34A1 were also significantly lower. Except for SLC22A7, the expression levels of SLC22A6, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were correlated with the clinical stage of ccRCC patients. The lower the expression levels of SLC22A6, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were, the later the clinical stage of ccRCC patients was. Further experiments revealed that the expression levels of SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were significantly associated with overall survival (OS) and disease-free survival (DFS) in ccRCC patients. High SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 expression predicted improved OS and DFS. Finally, GSE53757 and ICGC were used to revalidate the differential expression and clinical prognostic value. This study suggests that SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 may be potential targets for the clinical diagnosis, prognosis, and treatment of ccRCC patients.

A Group of miRNA as Candidates for Prognostic Biomarkers of Gastric Cancer Metastasis.

An association was found between reduced expression of miR-34a, miR-146a with both metastasis to regional lymph nodes (relative risk RR=10.50 and RR=5.25, respectively) and the development of distant metastases (RR=9.50 and RR=4, 40, respectively) in gastric cancer. They are excellent classifiers: AUC>0.9 for both miRNAs. The association of miR-335 expression with metastasis to the lymph nodes is much weaker, but it is also a good classifier for identifying a group with distant metastasis (RR=5.90). A correlation was found between the expression of miR-34a and miR-146a during metastasis, which is absent in non-metastatic tumors. Thus, miR-34a, miR-146a, and miR-335 miRNAs can be proposed as candidates for biomarkers of the risk of gastric cancer metastasis.

Comprehensive Analysis of Candidate Diagnostic and Prognostic Biomarkers Associated with Lung Adenocarcinoma.

BackgroundWe aimed to screen and identify central genetic and molecular targets involved in advancement of lung adenocarcinoma (LUAD) and to perform an integrated analysis and clinical validation.Material/MethodsThe GEO2R technique was utilized to assess differentially expressed genes (DEGs) among the gene sets GSE75037, GSE85716, and GSE118370. Subsequently, gene Ontology (GO) analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) analytical methods were executed to determine related biofunctions and signaling pathways, which were annotated with tools from the Database for Annotation, Visualization and Integrated Discovery (DAVID) resource. Then, a protein-protein interaction (PPI) network complex consisting of all detected DEGs was built with the STRING web interface. Cytohubba and MCODE plug-ins for Cytoscape software and Gene Expression Profiling Interactive Analysis (GEPIA) were employed to identify the hub genes. Finally, the mRNA expression of the identified hub genes was quantitatively validated by The Cancer Genome Atlas (TCGA) database analysis and real-time quantitative polymerase chain reaction (RT-qPCR).ResultsWe screened 146 upregulated DEGs and 431 downregulated DEGs with the criteria of |logFC| >1 and P<0.05, and the GO analysis indicated that DEGs were implicated in mitotic nuclear division (biological process, BP), the nucleus (cellular component, CC), and protein binding (molecular function, MF) and were associated with multiple KEGG pathways, such as the p53 signaling pathway in cancer. Then, the top 8 genes that predicted significantly different outcomes in LUAD patients were filtered from the DEGs and selected as hub genes. The TCGA database analysis and RT-qPCR results demonstrated that these genes were differentially expressed with the same trends in LUAD tissues compared with normal tissues.ConclusionsOverall, we propose that 8 genes (PECAM1, CDK1, MKI67, SPP1, TOP2A, CHEK1, CCNB1, and RRM2) might be novel hub genes strongly associated with the progression and prognosis of LUAD.

Early Amplified Respiratory Bioactive Lipid Response Is Associated With Worse Outcomes in Pediatric Influenza-Related Respiratory Failure.

BackgroundBiomarkers are needed for early identification of patients at risk of severe complications from influenza infection, including prolonged respiratory failure and death. Eicosanoids are bioactive lipid mediators with pro- and anti-inflammatory properties produced in response to infection. This study assessed the relationships between the host bioactive lipid response, influenza viral load, and clinical outcomes.MethodsInfluenza-positive, intubated children ≤18 years old were enrolled across 26 US pediatric intensive care units (PICUs). Mass spectrometry was used to measure >100 lipid metabolites in endotracheal and nasopharyngeal samples. Influenza viral load was measured by quantitative polymerase chain reaction.ResultsAge and bacterial co-infection were associated with multiple bioactive lipids (P < .05). Influenza viral load was lower in patients with bacterial co-infection compared with those without, and pro-inflammatory bioactive lipids positively correlated with viral load in bacterially co-infected children (P < .05). Lipids associated with disease resolution correlated with viral load in patients without bacterial co-infection (P < .01). After adjusting for age and bacterial co-infection status, elevated pro- and anti-inflammatory lipids measured early in the intensive care unit course were associated with higher mortality, whereas influenza viral load and endotracheal cytokine levels were not associated with clinical outcomes. Prostaglandin E2, arachidonic acid, docosahexaenoic acid, and 12-hydroxyeicosatetraenoic acid measured within 72 hours of PICU admission predicted death or prolonged (≥28 days) mechanical ventilator support (area under the curve, 0.72–0.79; P < .02) not explained by admission illness severity.ConclusionsChildren with influenza-related complications have early bioactive lipid responses that may reflect lung disease severity. Respiratory bioactive lipids are candidate prognostic biomarkers to identify children with the most severe clinical outcomes.

Candidate genes for predicting the survival of patients with gastric cancer: a study based on The Cancer Genome Atlas (TCGA) database.

BackgroundGastric cancer (GC) is the second most frequent cause of cancer-related mortality in the world, and the five-year survival rate for GC remains very low universally. In recent years, it has become a consensus that genetic changes are associated with carcinogenesis of GC, and precision medicine based on genetic changes is one of the most popular treatments for GC patients. However, the association between some genes and GC-related protein signaling pathways is still not well understood. This study revealed that seven genes were closely related to the survival probability in GC patients.MethodsWe downloaded the gene expression data of GC patients from The Cancer Genome Atlas (TCGA) databases, and integrated bioinformatic analysis was performed, such as differential gene expression analysis, including Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathways analyses, as well as survival analysis. The r package “survival” was used to analyze the Kaplan-Meier survival analysis, which showed the associations between specific gene expressions and the outcomes of patients with GC to identify which genes could be potential prognostic biomarkers.ResultsThis study revealed that seven genes: alcohol dehydrogenase 4 (ADH4), histamine receptor H3 (HRH3), neuropeptide Y2 receptor (NPY2R), apolipoprotein AI (APOA1), N-acetylgalactosaminyltransferase 14 (GALNT14), leucine-rich repeats and IQ motif containing 1 (LRRIQ1), and coiled-coil-domain-containing 57 (CCDC57). These seven genes were closely related to the survival probability of GC patients (P<0.05).ConclusionsOur study found seven genes which could be considered as candidate prognostic biomarkers and therapeutic targets.

PD64-11 OVEREXPRESSION OF LNCRNA SUCLG2-AS1 INHIBITS CELL PROLIFERATION, MIGRATION AND INVASION THROUGH INHIBITING MAPK PATHWAY IN RENAL CELL CARCINOMA

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology III (PD64)1 Apr 2020PD64-11 OVEREXPRESSION OF LNCRNA SUCLG2-AS1 INHIBITS CELL PROLIFERATION, MIGRATION AND INVASION THROUGH INHIBITING MAPK PATHWAY IN RENAL CELL CARCINOMA Zhang Kenan*, Gong Yanqing, Cai Lin, and Gong Kan Zhang Kenan*Zhang Kenan* More articles by this author , Gong YanqingGong Yanqing More articles by this author , Cai LinCai Lin More articles by this author , and Gong KanGong Kan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000981.011AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Pervious studies have revealed that long non-coding RNAs (lncRNAs) play an important role in renal cell carcinoma. However, the detailed roles of lncRNA SUCLG2-AS1 was rarely known and remained to be elucidated. METHODS: The genes of differential expression lncRNA were identified by TCGA.The relative expression level of SUCLG2-AS1 was determined by Real-Time qPCR in a total of 60 patients with clear cell renal cell carcinoma (ccRCC) and in different renal cell carcinoma (RCC) cell lines. Overexpression experiments were performed to investigate the biological roles of SUCLG2-AS1 on RCC cell proliferation, migration and invasion. Comprehensive transcriptional analysis, RNA-FISH and western blot were performed to explore the molecular mechanisms underlying the functions of SUCLG2-AS1. RESULTS: In this study, we found that SUCLG2-AS1 was downregulated in ccRCC tissues by analyzing TCGA online RNA-seq data. Moreover, decreased SUCLG2-AS1 expression level was positive associated with pathologic states and survival. Low expression of SUCLG2-AS1 was also confirmed in ccRCC tissues and RCC cell lines. In vitro, overexpression of SUCLG2-AS1 inhibits cell proliferation, migration and invasion in RCC cell lines. In a tumor xenograft model, we confirmed that SUCLG2-AS1 overexpression could significantly inhibit the growth of RCC. Mechanistically, we found that SUCLG2-AS1 was distributed mostly in the cytoplasm Furthermore, overexpression of SUCLG2-AS1 suppressed the expression of MAPK pathway related proteins in renal cell carcinoma. CONCLUSIONS: In conclusion, our findings demonstrated that SUCLG2-AS1 act as an suppressor gene in ccRCC, which may sever as a candidate prognostic biomarker for ccRCC patients. Source of Funding: This work was supported by the National Natural Science Foundation of China (grant 81572506), the Special Health Development Research Project of Capital (grant 2016-2-4074), and the Fundamental Research Funds for the Central Universities (grant BMU2018JI002). © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1304-e1304 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Zhang Kenan* More articles by this author Gong Yanqing More articles by this author Cai Lin More articles by this author Gong Kan More articles by this author Expand All Advertisement PDF downloadLoading ...

Zinc finger protein 703 induces EMT and sorafenib resistance in hepatocellular carcinoma by transactivating CLDN4 expression

Metastasis is one of the most common reasons of hepatocellular carcinoma (HCC) death; however, the molecular mechanism underlying HCC metastasis remains incompletely defined. Here we report a new function of Zinc Finger Protein 703 (ZNF703), a member of the NET/NlZ family of zinc finger transcription factors, in promoting hepatocellular carcinoma metastasis. We demonstrated that the overexpression of ZNF703 in human HCC tissue is correlated with tumor metastasis and recurrence, it is also related with the prognosis and survival rate of patients. ZNF703 overexpression promotes HCC progression in vitro and in vivo, whereas ZNF703 knockdown has the opposite effect. In addition, ZNF703 induces epithelialmesenchymal transition (EMT) via directly binding to the CLDN4 promoter and transactivating CLDN4 expression. Downregulation of CLDN4 can attenuate ZNF703-mediated HCC metastasis, whereas upregulation of CLDN4 can reverse the decreased metastasis induced by ZNF703 knockdown. Our data revealed that ZNF703 expression is correlated with CLDN4 level, the overexpression of both ZNF703 and CLDN4 are leaded to poorer prognosis of patients with HCC. Moreover, ZNF703 knockdown can enhance the sensitivity of HCC cell to sorafenib, whereas ZNF703 overexpression has the opposite effect. These results suggested that ZNF703 might be a potential target for cancer therapies and a candidate prognostic biomarker for predicting whether patients with HCC are befitting for sorafenib treatment.

Identification of miRNA-mRNA associations in hepatocellular carcinoma using hierarchical integrative model

BackgroundThe established role miRNA-mRNA regulation of gene expression has in oncogenesis highlights the importance of integrating miRNA with downstream mRNA targets. These findings call for investigations aimed at identifying disease-associated miRNA-mRNA pairs. Hierarchical integrative models (HIM) offer the opportunity to uncover the relationships between disease and the levels of different molecules measured in multiple omic studies.MethodsThe HIM model we formulated for analysis of mRNA-seq and miRNA-seq data can be specified with two levels: (1) a mechanistic submodel relating mRNAs to miRNAs, and (2) a clinical submodel relating disease status to mRNA and miRNA, while accounting for the mechanistic relationships in the first level.ResultsmRNA-seq and miRNA-seq data were acquired by analysis of tumor and normal liver tissues from 30 patients with hepatocellular carcinoma (HCC). We analyzed the data using HIM and identified 157 significant miRNA-mRNA pairs in HCC. The majority of these molecules have already been independently identified as being either diagnostic, prognostic, or therapeutic biomarker candidates for HCC. These pairs appear to be involved in processes contributing to the pathogenesis of HCC involving inflammation, regulation of cell cycle, apoptosis, and metabolism. For further evaluation of our method, we analyzed miRNA-seq and mRNA-seq data from TCGA network. While some of the miRNA-mRNA pairs we identified by analyzing both our and TCGA data are previously reported in the literature and overlap in regulation and function, new pairs have been identified that may contribute to the discovery of novel targets.ConclusionThe results strongly support the hypothesis that miRNAs are important regulators of mRNAs in HCC. Furthermore, these results emphasize the biological relevance of studying miRNA-mRNA pairs.

Synergistic effects of depression and NR3C1 methylation on prognosis of acute coronary syndrome

High levels of methylation in the GR gene (nuclear receptor subfamily 3, group C, member 1; NR3C1) have been associated with depression and cardiovascular risk. This study aimed to investigate whether NR3C1 methylation status was associated with the long-term prognosis of acute coronary syndrome (ACS) considering depression and cardiovascular status at the early phase of ACS. A total of 969 patients with recent ACS were recruited at a tertiary university hospital in Korea. Baseline evaluations were made from 2007 to 2012, including DSM-IV depressive disorder, NR3C1 methylation, and various demographic and clinical characteristics such as cardiovascular risk markers. Over a 5~12 year follow-up after the index ACS, time to major adverse cardiac event (MACE) was investigated using Cox regression models. Higher NR3C1 methylation status was associated with depression and several cardiovascular risk markers at baseline. NR3C1 hypermethylation predicted worse long-term prognosis of ACS only in the presence of depressive disorder with significant synergistic interaction terms and independent of potential confounding factors. Synergistic effects of depressive disorder and NR3C1 hypermethylation on long-term cardiac outcomes in ACS were found. NR3C1 methylation status represents a candidate prognostic biomarker for ACS in combination with a diagnosis of depressive disorder. Further research is needed to ascertain the generalisability of these findings.