Novel Biomarker For Prognosis Research Articles

The potential prognostic values of the ADAMTS-like protein family: an integrative pan-cancer analysis.

BackgroundA disintegrin-like and metalloproteinase domain with thrombospondin type 1 motifs (ADAMTS)-like proteins, including ADAMTSL1-6 and papilin, which are part of the mammalian ADAMTS superfamily, appear to be relevant to extracellular matrix function and the regulation of ADAMTS protease activity. Their roles in tumor initiation and progression and regulating the tumor microenvironment (TME) are now recognized.MethodsIn the present study, a comprehensive investigation of the pan-cancer effects of ADAMTSLs and their associations with patient survival, drug responses, and the TME was performed by integrating The Cancer Genome Atlas (TCGA) data and annotated data resources.ResultsThe expression of ADAMTSL family members was found to be dysregulated in many cancer types. More importantly, their expression was frequently associated with patients’ overall survival (OS), drug responses, and the TME. ADAMTSL1, ADAMTSL4, and ADAMTSL5 were primarily associated with aggressive phenotypes, while PAPLN was more frequently associated with a favorable prognosis. In a non-small cell lung cancer (NSCLC) cohort, Thrombospondin Type 1 Domain Containing 4 (THSD4) (ADAMTSL6) and Papilin (PAPLN) were associated with immune checkpoint inhibitor (ICI) sensitivity in samples from the Gene Expression Omnibus repository (GSE135222). Twenty and 30 proteins related to THSD4 and PAPLN, respectively, were identified through a proteomic analysis of 18 Chinese lung adenocarcinoma patients.ConclusionsOur findings extend understandings of the role of the ADAMTSL family in cancers and are a valuable resource on their clinical utility. This article provides insight into the clinical importance of next-generation sequencing technology to identify novel biomarkers for prognosis and investigate therapeutic strategy for clinical benefit.

A Novel Prognostic Biomarker LPAR6 in Hepatocellular Carcinoma via Associating with Immune Infiltrates.

Background and AimsLPAR6 is the most recently determined G protein-coupled receptor of lysophosphatidic acid, and hardly any study has demonstrated the performance of LPAR6 in cancers. We sought to clarify the relationship of LPAR6 to prognosis potential and tumor infiltration immune cells in different cancers.MethodsThe expression of LPAR6 and its clinical characteristics were evaluated on various databases. The association between LPAR6 and immune infiltrates of various types of cancer were investigated via TIMER.ResultsWe determined that higher LPAR6 expression level was associated with a better overall survival. Additionally, high LPAR6 expression level was significantly associated with better disease-specific survival (DSS) in bladder cancer, and better overall survival (OS)/ progression-free survival (PFS)/ distant metastasis-free survival (DMFS)/ relapse-free survival (RFS) in breast cancer and some other types of cancers. Moreover, LPAR6 significantly affects the prognosis of various cancers via The Cancer Genome Atlas (TCGA). Further research exposed that the mRNA level of LPAR6 was positively coordinated with infiltrating levels of devious immune cells in hepatocellular carcinoma.ConclusionsOur results imply that LPAR6 is associated with prognosis potential and immune infiltration levels in liver cancer. Moreover, LPAR6 expression possibly contributes to the activation of CD8+ T, naive T, effector T cells and natural killer cells and inactivates T regulatory cells, decreases T cell exhaustion and regulate T helper cells in liver cancer. These discoveries imply that LPAR6 could be a novel biomarker of prognosis for indicating prognosis potential and immune-infiltrating level in hepatocellular carcinoma.

Prognostic and pathogenic role of CXC motif ligand 16 in sepsis

Chemokine CXC motif ligand 16 (CXCL16) is an important mediator that has been shown to participate in various human diseases. The role of CXCL16 in the immunopathology of sepsis remains unidentified. In this study, we found that human patients with sepsis had significantly higher soluble levels of serum CXCL16 than healthy volunteers on day of intensive care unit (ICU) admission. Soluble CXCL16 remained significantly up-regulated in the patients with sepsis, which correlated with disease severity. Furthermore, nonsurvivors displayed significantly higher admission levels of soluble CXCL16 compared with survivors of septic patients. Soluble CXCL16 levels revealed significant prognostic value for 28-day mortality, and CXCL16 was shown to be an independent predictor of 28-day mortality in the patients with sepsis. In a murine model of cecal ligation and puncture (CLP)-induced nonsevere sepsis, supplementation of recombinant CXCL16 protein could increase sepsis-induced mortality and tissue injury. Conversely, neutralizing CXCL16 by anti-CXCL16 monoclonal antibody could decrease mortality and tissue injury in CLP-induced severe sepsis. However, CXCL16 did not affect the ability of these mice to clear bacteria in CLP. Taken together, CXCL16 could be related to sepsis not only as a novel biomarker of prognosis, but also as a potential target for therapeutic intervention.

N6-Methylandenosine-Related lncRNA Signature Is a Novel Biomarkers of Prognosis and Immune Response in Colon Adenocarcinoma Patients

BackgroundColon adenocarcinoma (COAD) is the most common type of colon cancer. To date, however, the prognostic values of m6A RNA methylation-related long non-coding RNAs (lncRNAs) in COAD are largely unknown.Materials and MethodsThe m6A-related lncRNAs were identified from The Cancer Genome Atlas (TCGA) data set. Univariate and multivariate Cox regression analyses were performed to explore the prognostic m6A-related lncRNAs. Consistent clustering analysis was performed to classify the COAD patients into different subgroups based on the expression of m6A-related lncRNAs. The potential biological functions as well as differences in the stemness index and tumor immune microenvironment between different subgroups were analyzed. The prognostic m6A-related lncRNAs were used to establish an m6A-related lncRNA risk model to predict prognosis and survival status.ResultsWe identified 31 m6A-associated lncRNAs with prognostic values from the TCGA data set. Based on the expression of prognostic m6A-associated lncRNAs, TCGA-COAD patients were classified into three clusters using consistent clustering analysis. There was a low correlation of tumor stemness between the three clusters but a significant correlation with the tumor immune microenvironment as well as the tumor mutational load. Thirty-one prognostic-related m6A-associated lncRNAs were used to construct a risk model, which was further determined by survival analysis, receiver operating characteristic (ROC) curve, and univariate and multifactor Cox analysis. The m6A-related risk model demonstrates good performance in predicting prognosis and survival status. The model-based high-risk group exhibited poorer overall survival (OS) compared with the low-risk group.ConclusionIn this study, we construct a risk model that consists of 31 m6A-related lncRNAs with independent prognostic values in COAD. Our study shows the critical roles of these 31 m6A-related lncRNAs in the tumor immune microenvironment, indicating the prospect of informing prognostic stratification and the development of immunotherapeutic strategies for COAD patients.

A novel long non-coding RNA AC073352.1 promotes metastasis and angiogenesis via interacting with YBX1 in breast cancer

Breast cancer is the major cause of cancer death worldwide in women. Patients with metastasis have poor prognosis and the mechanisms of breast cancer metastasis are not completely understood. Long non-coding RNAs (lncRNAs) have been shown to have crucial roles in breast cancer development and progression. However, the underlying mechanisms by which lncRNA-driven breast cancer metastasis are unknown. The main objective of this paper is to explore a functional lncRNA and its mechanisms in breast cancer. Here we identified a novel lncRNA AC073352.1 that was significantly upregulated in breast cancer tissues and was associated with advanced TNM stages and poor prognosis in breast cancer patients. In addition, AC073352.1 was found to promote the migration and invasion of breast cancer cells in vitro and enhance breast cancer metastasis in vivo. Mechanistically, we elucidated that AC073352.1 interacted with YBX1 and stabilized its protein expression. Knock down of YBX1 reduced breast cancer cell migration and invasion and could partially reverse the stimulative effects of AC073352.1 overexpressed on breast cancer metastasis. Moreover, AC073352.1 might be packaged into exosomes by binding to YBX1 in breast cancer cells resulting in angiogenesis. Collectively, our results demonstrated that AC073352.1 promoted breast cancer metastasis and angiogenesis via binding YBX1, and it could serve as a promising, novel biomarker for prognosis and a therapeutic target in breast cancer.

Identification of potential biomarkers associated with poor prognosis in oral squamous cell carcinoma through integrated bioinformatics analysis: A pilot study

BackgroundOral squamous cell carcinoma (OSCC) is the most frequent subtype of oral cancer with 90% of the OC cases. The mortality rate of OSCC is high and the overall survival of the patients is 50%. There is a need to discover novel biomarkers for prognosis of OSCC. MethodsThe miRNA dataset GSE107830 was downloaded from the GEO database and analyzed to identify differentially expressed miRNAs (DEMs) in OSCC patients with poor prognosis compared to favorable prognosis patients. A protein-protein interaction network was constructed and analyzed. The most significant clusters in the PPI network were identified, and the biological processes (BPs) and pathways associated with each of the clusters were studied. The hub genes were identified and the survival analysis was performed to examine the potential prognostic role of the hub genes in OSCC. ResultsA total of 35 DEMs were found with the criteria of P < 0.001 and absolute value of Log2 fold change > 0.58. The most significant pathways and BPs affected in poor prognosis group were associated with ubiquitination and RNA splicing. The survival analysis revealed that the aberrant expression of 22 hub genes was significantly associated with worse overall survival in OSCC. The most significant Kaplan-Meier curves were achieved from EGF, RTN4, RAN, ACTB, and CYCS genes with the Logrank test P-value of <0.01. ConclusionsThe results showed that a total of 22 genes including EGF, RTN4, RAN, ACTB, and CYCS may be considered as potential biomarkers for prognostic aims of OSCC.

Investigation of lncRNA-mRNA co-expression network in ETV6-RUNX1-positive pediatric B-cell acute lymphoblastic leukemia.

ETV6/RUNX1 gene fusion is the most common chromosomal translocation abnormality occurred in pediatric B-cell acute lymphoblastic leukemia (B-ALL). Compared with ETV6-RUNX1-negative patients, ETV6-RUNX1-positive patients possess more improved treatment strategies but higher risk to relapse. In this research, the potential gene interaction networks were constructed intending for elucidating the pathogenesis of B-ALL. We performed the weighted gene co-expression network analysis (WGCNA) to assess the involvement of lncRNA-mRNA pairs in B-ALL patients consisting of 24 ETV6-RUNX1-positive patients and 18 ETV6-RUNX1-negative patients and found a module that was significantly associated with positive/negative trait. Gene Ontology analysis showed that mRNAs in this module were enriched in the positive regulation of MAPK cascade, positive regulation of JNK cascade, and myeloid cell differentiation pathway. To further investigate the relationship between lncRNAs and mRNAs in this significant module, we constructed the lncRNA-mRNA co-expression network. 3 lncRNAs (RP11-170J3.2, RP11-135F9.1 and RP1-151B14.9) were found at the core of the lncRNA-mRNA co-expression network, which had the most co-expression connections with mRNAs. And several related mRNAs (ACTN1, TNFRSF21 and NLRP3) had a significant correlation with the patient survival prediction. Our findings may explicate the pathogenesis of B-ALL, and the disease-associated genes could provide clues to find novel biomarkers for prognosis.

Identification of VWF as a Novel Biomarker in Lung Adenocarcinoma by Comprehensive Analysis.

Lung adenocarcinoma (LUAD) is one of the most malignant tumors with high morbidity and mortality worldwide due to the lack of reliable methods for early diagnosis and effective treatment. It’s imperative to study the mechanism of its development and explore new biomarkers for early detection of LUAD. In this study, the Gene Expression Omnibus (GEO) dataset GSE43458 and The Cancer Genome Atlas (TCGA) were used to explore the differential co-expressed genes between LUAD and normal samples. Three hundred sixity-six co-expressed genes were identified by differential gene expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA) method. Those genes were mainly enriched in ameboidal-type cell migration (biological process), collagen-containing extracellular matrix (cell component), and extracellular matrix structure constituent (molecular function). The protein-protein network (PPI) was constructed and 10 hub genes were identified, including IL6, VWF, CDH5, PECAM1, EDN1, BDNF, CAV1, SPP1, TEK, and SELE. The expression level of hub genes was validated in the GEPIA database, compared with normal tissues, VWF is lowly expressed and SPP1 is upregulated in LUAD tissues. The survival analysis showed increased expression of SPP1 indicated unfavorable prognosis whereas high expression of VWF suggested favorable prognosis in LUAD (p < 0.05). Based on the immune infiltration analysis, the relationship between SPP1 and VWF expression and macrophage, neutrophil, and dendritic cell infiltration was weak in LUAD. Quantitative real-time PCR (qRT-PCR) and western blotting were used to validate the expression of VWF and SPP1 in normal human bronchial epithelial (HBE) cell and three LUAD cell lines, H1299, H1975, and A549. Immunohistochemistry (IHC) was further performed to detect the expression of VWF in 10 cases LUAD samples and matched normal tissues. In summary, the data suggest that VWF is a potential novel biomarker for prognosis of LUAD.

Programmed Death Ligand 1 Expression as a Prognostic Marker in Patients with Advanced Biliary Tract Cancer

Background: Biliary tract cancer (BTC) is associated with poor prognosis because of its aggressive and heterogeneous nature. Programmed death ligand 1 (PD-L1) has been considered a novel biomarker for prognosis and response of immune checkpoint inhibitors in various tumors. However, there are limited data reporting on the role of PD-L1 in advanced BTC patients. Patients and Methods: We analyzed 186 patients with advanced BTC who received palliative gemcitabine and platinum between May 2010 and December 2019. All patients were evaluated for PD-L1 expression by combined positive score positivity. Results: Of the 186 patients, the primary tumor location was intrahepatic cholangiocarcinoma (IHCC) in 72 (38.7%), extrahepatic cholangiocarcinoma (EHCC) in 90 (48.4%), and gallbladder (GB) cancer in 24 (12.9%). Among all the patients, 53 (28.5%) had PD-L1 positivity. The median overall survival (OS) of patients with PD-L1 positivity or negativity was 12.1 and 15.4 months, respectively. The median progression-free survival (PFS) in patients with PD-L1 positivity or negativity was 5.7 and 7.1 months, respectively. OS and PFS were not statistically different between groups. In subgroup analysis, EHCC patients with PD-L1 negativity had more favorable OS (17.2 vs. 11.6 months, p = 0.002) and PFS (7.8 vs. 5.4 months, p = 0.005) than those who were PD-L1-positive. However, this finding was not reproduced in patients with IHCC or GB cancer. Conclusion: This study demonstrated that PD-L1 expression might be a novel prognostic biomarker in patients with EHCC but not in patients with IHCC or GB cancer.

Identification of HOXA1 as a Novel Biomarker in Prognosis of Head and Neck Squamous Cell Carcinoma.

Hox genes, a highly conserved homolog in most animals, play vital functions in cell development and organ formation. In recent years, researchers have discovered that it can act as a tumor regulator, and its members can participate in tumorigenesis by regulating receptor signaling, cell differentiation, apoptosis, migration, EMT, and angiogenesis. Hox genes and which major members play a vital role in the progress of head and neck squamous cell carcinoma (HNSCC) is still unclear. After analyzing the expression differences and prognostic value of all Hox genes through the TCGA-HNSC database, we use histochemistry stains in 52 pairs of HNSCC slices to verify the expression level of the key member-HOXA1. In correlation analysis, we found that high HOXA1 expression is related to poor pathological grade (p = 0.0077), advanced T stage (p = 0.021) and perineural invasion (PNI) (p = 0.0019). Furthermore, we used Cox univariate and multivariate regression analysis to confirm the independent predictive power of HOXA1 expression. To explore the underlying mechanisms behind HOXA1, we ran GSVA and GSEA and found fourteen mutual signaling pathways, including neuroprotein secretion and transport, tumor-associated signaling pathways, cell adhere junction and metabolic reprogramming. Finally, we found that the high expression of HOXA1 is significantly related to the decrease of CD8+ T cell infiltration and the decline of DNA methylation level. Our findings demonstrated that HOXA1, as a notable member of the HOX family, maybe an independent prognostic indicator in HNSCC.

DUOX2 As a Potential Prognostic Marker which Promotes Cell Motility and Proliferation in Pancreatic Cancer.

DUOX2 has been reported to highly express in several types of cancers. However, the prognostic significance and the biological function of DUOX2 expression with pancreatic cancer (PC) still remain unclear. The present study is aimed at investigating whether DUOX2 could act as a novel biomarker of prognosis and evaluating its effect on PC cell progression. The mRNA and protein expression of DUOX2 in PC cells and tissues were assessed by quantitative real-time PCR (RT-qPCR) and immunohistochemistry. The effect of DUOX2 expression on PC cell motility and proliferation was evaluated in vitro. The correlation between DUOX2 mRNA expression and clinicopathological features and its prognostic significance were analyzed according to the Gene Expression Profiling Interactive Analysis (GEPIA) website based on The Cancer Genome Atlas (TCGA) and the GTEx databases combined with our clinical information. According to bioinformatics analysis, we forecasted the upstream transcription factors (TFs) and microRNA (miRNA) regulatory mechanism of DUOX2 in PC. The expression of DUOX2 at transcriptional and protein level was dramatically increased in PC specimens when compared to adjacent nontumor specimens. Functionally, DUOX2 knockdown inhibited cell motility and proliferation activities. Our clinical data revealed that the patients had better postoperative overall survival (OS) with lower expression of DUOX2, which is consistent with GEPIA data. Multivariate analysis revealed that high DUOX2 expression was considered as an independent prognostic indicator for OS (P = 0.031). Based on Cistrome database, the top 5 TFs of each positively and negatively association with DUOX2 were predicted. hsa-miR-5193 and hsa-miR-1343-3p targeting DUOX2 were forecasted from TargetScan, miRDB, and DIANA-TarBase databases, which were negatively correlated with OS (P = 0.043 and P = 0.0088, respectively) and DUOX2 expression (P = 0.0093 and P = 0.0032, respectively) in PC from TCGA data. These findings suggest that DUOX2 acts as a promising predictive biomarker and an oncogene in PC, which could be a therapeutic target for PC.

Circular RNA circ-NT5C2 acts as a potential novel biomarker for prognosis of osteosarcoma.

We detected some serious inaccuracies and mistakes. Therefore, the article, "Circular RNA circ-NT5C2 acts as a potential novel biomarker for prognosis of osteosarcoma, by W.-B. Nie, L.-M. Zhao, R. Guo, M.-X. Wang, F.-G. Ye, published in Eur Rev Med Pharmacol Sci 2018; 22 (19): 6239-6244-DOI: 10.26355/eurrev_201810_16030-PMID: 30338784" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/16030.

VALUE OF COPEPTIN MEASUREMENT AS A NOVEL BIOMARKER FOR PROGNOSIS INACUTE HEART FAILURE

Abstract Background: Copeptin, C-terminal segment of pro-arginine vasopressin, is expected to be a strong novel biomarker for prognosis in acute heart failure (AHF).Participants & Methods: The study included 45 patients with acute decompensated heart failure(ADHF) to assess the relationship of serum copeptin level on admission and 72 hours after admission with adverse cardiac events (death, re-hospitalization and arrhythmias) in patients hospitalized for (ADHF) between May 2019 and November 2019 with median follow up period 6 months.Results: In this study,15 patients died, re-admission occurred in 22 patients and arrhythmias were documented in 14 patients with atrial fibrillation (n=9) and ventricular arrhythmias (n=5). Mortality rate was higher among elder smoker patients with higher heart rate, low left ventricular systolic function, higher rates of arrhythmias, impaired kidney function and high copeptin level.Furthermore, copeptin level at day 1 with cutoff value of ˃2.54 pmol/l predicted mortality with sensitivity 86.67% and specificity 53.33% while copeptin level at day 3 with cutoff value ˃ 2.74 pmol/l predicted mortality with sensitivity 93.33% and specificity 83.33%.Finally, change in copeptin level between day 1 and day 3 was associated with increased mortality. (p˂0.001)Conclusion: Copeptin is suggested to be a strong biomarker to predict adverse clinical outcomes in patients with acute decompensated heart failure including death.

Systematic Evaluation of Urinary VCAM1 as Novel Biomarker for Prognosis of Lupus Nephritis.

Lupus nephritis was established as the major cause of morbidity and mortality in systemic lupus erythematosus (SLE) patients. This severity could be monitored by laboratory prognosis with accuracy and specificity for the disease. Recently, various SLE laboratory investigations still have had improper prognosis and also possibly causing tissue injury in the patients. The present study thus aimed to systematically explore a novel urinary protein for further development into a prognosis biomarker in patients. Several urinary proteins that previously were reported with abnormal expression in SLE patients between 2014 - 2019 were comprehensively collected. These proteins were also analyzed for functional category and sites of expression using STIRNG, FUNRICH, and Uniport database. Thereafter, the level of altered protein candidate was then validated by western blotting, correlation analysis, and diagnostic performance. Vascular cell adhesion molecule-1 (VCAM1) protein was found in higher levels and also specific in SLE patients with nephritis. Moreover, VCAM1 has a role in immune response, inflammation, is expressed on plasma membrane of renal cells, and has the ability to secret into urine. The level of VCAM1 in urine of SLE patients was significantly higher than in healthy controls. The area under ROC curve (AUC) was also 0.891. Furthermore, the level of VCAM1 was dramatically associated with the severity of renal insufficiency (r = 0.738). VCAM1 may be a novel urinary biomarker for reliable prognosis of nephritis severity in SLE patients.

A bioinformatics analysis to identify novel biomarkers for prognosis of pulmonary tuberculosis

BackgroundDue to the fact that pulmonary tuberculosis (PTB) is a highly infectious respiratory disease characterized by high herd susceptibility and hard to be treated, this study aimed to search novel effective biomarkers to improve the prognosis and treatment of PTB patients.MethodsFirstly, bioinformatics analysis was performed to identify PTB-related differentially expressed genes (DEGs) from GEO database, which were then subjected to GO annotation and KEGG pathway enrichment analysis to initially describe their functions. Afterwards, clustering analysis was conducted to identify PTB-related gene clusters and relevant PPI networks were established using the STRING database.ResultsBased on the further differential and clustering analyses, 10 DEGs decreased during PTB development were identified and considered as candidate hub genes. Besides, we retrospectively analyzed some relevant studies and found that 7 genes (CCL20, PTGS2, ICAM1, TIMP1, MMP9, CXCL8 and IL6) presented an intimate correlation with PTB development and had the potential serving as biomarkers.ConclusionsOverall, this study provides a theoretical basis for research on novel biomarkers of PTB, and helps to estimate PTB prognosis as well as probe into targeted molecular treatment.

Identification of snoRNA SNORA71A as a Novel Biomarker in Prognosis of Hepatocellular Carcinoma.

Background Small nucleolar RNAs (snoRNAs) have been proved to play important roles in various cellular physiological process. Recently, dysregulation of snoRNA SNORA71A has been found involved in tumorigenesis of various malignant cancers. However, the emerging effects of SNORA71A in hepatocellular carcinoma (HCC) remain largely unclear. In this study, we aimed to explore the SNORA71A expression and its underlying significance in HCC. Methods Expression of SNORA71A in cell lines and clinical specimens was measured by quantitative real-time PCR. Then, all enrolled HCC patients were divided into low and high SNORA71A expression subgroups and then they were compared in the aspects of clinical features as well as survival outcome by respective statistical analysis methods. Results SNORA71A was significantly downexpressed in SK-HEP-1 (P = 0.001), Huh-7 (P < 0.001), Hep3B (P < 0.001), and clinical HCC specimens (P = 0.006). Comparing the clinical features between SNORA71A expression subgroups, it showed that low SNORA71A expression was significantly associated with large tumor diameter, multiple lesions, capsular invasion, bad tumor differentiation, and TNM stage (P < 0.05). Furthermore, it was found that HCC patients with lower SNORA71A expression had higher risk in postoperative tumor relapse (median time: 9.5 vs. 35.2 months; low vs. high; P < 0.001) and poor overall survival (median time: 36.8 vs. 52.9 months; low vs. high; P < 0.001). Besides, SNORA71A expression served as independent risk factors for tumor-free (HR = 0.450; 95% CI [0.263-0.770]; P = 0.004) and long-term survival (HR = 0.289; 95% CI [0.127-0.657]; P = 0.003). Conclusions Our study for the first time demonstrated that downregulation of SNORA71A could serve as a novel biomarker for clinical assessment and prognostic prediction of HCC patients.

High expression of TCN1 is a negative prognostic biomarker and can predict neoadjuvant chemosensitivity of colon cancer

Transcobalamin (TCN1) is a vitamin B12 (cobalamin)-binding protein that regulates cobalamin homeostasis. Recent studies and bioinformatic analyses have found that TCN1 is highly expressed in cancer tissues and is associated with tumour aggressiveness and poor prognosis. The present study aimed to detect TCN1 as a novel biomarker for prognosis and chemosensitivity of colon cancer. Next-generation sequencing showed that TCN1 was one of several upregulated mRNAs in colon cancer, which was verified by further bioinformatics analyses. Western blotting (n = 9) and quantitative real time polymerase chain reaction (qRT-PCR, n = 30) revealed that TCN1 was highly expressed in colon cancer tissues at both the protein and mRNA level. A total of 194 cases of colon cancer were examined by immunohistochemistry and revealed that TCN1 expression level was related to advanced stages (P < 0.005). Kaplan–Meier analysis verified that patients with lower TCN1 expression usually had longer overall survival (P = 0.008). In addition, TCN1 was highly expressed in pulmonary metastatic tumour tissues (n = 37, P = 0.025) and exhibited higher levels in right-sided colon cancer than in left-sided colon cancer (P = 0.029). TCN1 expression in specimens that had received neoadjuvant chemotherapy decreased compared with that in colonoscopy biopsy tissues (n = 42, P = 0.009). Further bioinformatics analyses verified that apoptosis pathways might have a role in high TCN1 expression. All the studies revealed that TCN1 expression in colon cancer was significantly associated with malignant biological behaviour. Therefore, TCN1 could be used as a novel biomarker for colon cancer aggressiveness and prognosis and might also be a potential biomarker for predicting neoadjuvant chemosensitivity.

110 RNA expression analysis in stage IVA-B cutaneous T-cell lymphoma to identify novel biomarkers of prognosis and diagnosis

Cutaneous T-cell lymphoma (CTCL) is a primary non-Hodgkin lymphoma and the most common primary cutaneous lymphoma. Due to its varied clinical and histological presentation, the accurate diagnosis of CTCL is difficult and therefore delayed; in advanced stages, CTCL is incurable and often fatal, though treatment-resistant phenotypes and survival time can be difficult to predict. There remains an unmet need for new and more effective diagnostic and prognostic indicators and novel therapies. To this end, malignant cells were isolated from the peripheral blood of 15 CTCL patients using antibody-magnetic bead or FACS sorting for CD3+CD4+ and CD7- and/or CD26- based on the known aberrant phenotype of the patient or positive selection for CD45RO+ CD4+ T cells in 3 healthy controls.

LncRNA and mRNA signature for prognosis prediction of glioblastoma.

Aims: We aimed to find out potential novel biomarkers for prognosis of glioblastoma (GBM). Materials & methods: We downloaded mRNA and lncRNA expression profiles of 169 GBM and five normal samples from The Cancer Genome Atlas and 129 normal brain samples from genotype-tissue expression. We use R language to perform the following analyses: differential RNA expression analysis of GBM samples using 'edgeR' package, survival analysis taking count of single or multiple gene expression level using 'survival' package, univariate and multivariate Cox regression analysis using Cox function plugged in 'survival' package. Gene ontology and Kyoto encyclopedia of genes and genomes pathway analysis were performed using FunRich tool online. Results and conclusion: We obtained differentially DEmRNAs and DElncRNAs in GBM samples. Most prognostically relevant mRNAs and lncRNAs were filtered out. 'GPCR ligand binding' and 'Class A/1' are found to be of great significance. In short, our study provides novel biomarkers for prognosis of GBM.

CREB1-induced lncRNA LEF1-AS1 contributes to colorectal cancer progression via the miR-489/DIAPH1 axis

Long non-coding RNAs (lncRNAs) have been identified as new regulatory factors in tumor progression. Lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1) was a recently identified lncRNA. This research aimed to investigate the roles and mechanisms of LEF1-AS1 in colorectal cancer (CRC). We firstly showed that LEF1-AS1 expression was upregulated in human CRC tissues and cell lines. LEF1-AS1 upregulation was demonstrated to be induced by CREB1. Clinical study revealed that high LEF1-AS1 expression was positively associated with histological grade, lymph nodes metastasis, and decreased survivals of CRC patients. Functionally, down-regulation of LEF1-AS1 using si-LEF1-AS1 decreased cell growth, migration and invasion, as well as increased apoptosis in CRC cells. Mechanically, LEF1-AS1 functioned as competing endogenous RNA (ceRNA) for miR-489 to positively recover DIAPH1, thus playing an oncogenic role in CRC pathogenesis. Overall, our observations identified a novel CRC-related lncRNA LEF1-AS1 and discovered a critical role for this lncRNA as a ceRNA in CRC pathogenesis, suggesting that it may serve as a novel biomarker for prognosis and act as a therapeutic target for CRC treatment.