scholarly journals The prognostic value of lncRNA SNHG4 and its potential mechanism in liver cancer

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Yan Jiao ◽  
Yanqing Li ◽  
Baoxing Jia ◽  
Qingmin Chen ◽  
Guoqiang Pan ◽  
...  

Abstract Background and object: Emerging evidence shows that non-coding RNA functions as new gene regulators and prognostic markers in several cancers, including liver cancer. Here, we focused on the small nucleolar RNA host gene 4 (SNHG4) in liver cancer prognosis based on The Cancer Genome Atlas (TCGA) data. Methods: The expression data and clinical information were downloaded from TCGA. Chi-square tests evaluated the correlation between SNHG4 expression and clinical parameters. Differences in survival between high and low expression groups (optic cutoff value determined by ROC) from Cox regression analysis were compared, and P-value was calculated by a log-rank test. Kaplan–Meier curves were compared with the log-rank test. GSEA and ceRNA network were conducted to explore the potential mechanism. Results: Data mining of lncRNA expression data for 371 patients with primary tumor revealed overexpression of SNHG4 in liver cancer. High SNHG4 expression was correlated with histological type (P = 0.01), histologic grade (P = 0.001), stage (P = 0.01), T classification (P = 0.004) and survival status (P = 0.013). Patients with high SNHG4 expression had poor overall survival and relapse-free survival compared with those with low SNHG4 expression. Multivariate analysis identified SNHG4 as an independent prognostic factor of poor survival in liver cancer. GSEA revealed related signaling pathway and ceRNA network explored the further mechanism. Conclusion: High SNHG4 expression is an independent predictor of poor prognosis in liver cancer.

2019 ◽  
Vol 28 (4) ◽  
pp. 439-447 ◽  
Author(s):  
Yan Jiao ◽  
Yanqing Li ◽  
Bai Ji ◽  
Hongqiao Cai ◽  
Yahui Liu

Background and Aims: Emerging studies indicate that long noncoding RNAs (lncRNAs) play a role as prognostic markers in many cancers, including liver cancer. Here, we focused on the lncRNA lung cancer-associated transcript 1 (LUCAT1) for liver cancer prognosis. Methods: RNA-seq and phenotype data were downloaded from the Cancer Genome Atlas (TCGA). Chisquare tests were used to evaluate the correlations between LUCAT1 expression and clinical features. Survival analysis and Cox regression analysis were used to compare different LUCAT1 expression groups (optimal cutoff value determined by ROC). The log-rank test was used to calculate the p-value of the Kaplan-Meier curves. A ROC curve was used to evaluate the diagnostic value. Gene Set Enrichment Analysis (GSEA) was performed, and competing endogenous RNA (ceRNA) networks were constructed to explore the potential mechanism. Results: Data mining of the TCGA -Liver Hepatocellular Carcinoma (LIHC) RNA-seq data of 371 patients showed the overexpression of LUCAT1 in cancerous tissue. High LUCAT1 expression was associated with age (p=0.007), histologic grade (p=0.009), T classification (p=0.022), and survival status (p=0.002). High LUCAT1 patients had a poorer overall survival and relapse-free survival than low LUCAT1 patients. Multivariate analysis identified LUCAT1 as an independent risk factor for poor survival. The ROC curve indicated modest diagnostic performance. GSEA revealed the related signaling pathways, and the ceRNA network uncovered the underlying mechanism. Conclusion: High LUCAT1 expression is an independent prognostic factor for liver cancer.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14541-e14541
Author(s):  
Gunjesh Kumar Singh ◽  
Hollis D'souza ◽  
Sujay Srinivas ◽  
Dilip Harindran Vallathol ◽  
Mounika Boppana ◽  
...  

e14541 Background: Anti-VEGF antibody Bevacizumab (Avastin: Roche Pharma AG) is the recommended drug for recurrent glioma. Multiple low-cost bio-similars of this drug are now available however their clinical efficacy has never been compared against the original molecule. The aim of the current analysis is to compare the overall survival (OS) between recurrent glioma patients with bio-similar and innovator molecule. Methods: Adult recurrent glioma patients treated with bevacizumab from 1st July 2015 to 30th July 2019 were identified from the Neuro-Medical Oncology database. These patients were either offered Avastin or Bevacizumab biosimilar (BevaciRel: Reliance Life sciences or Bryta: Zydus Oncosciences) depending upon the financial affordability. The primary endpoint of the study was OS. It was defined as the time in months from the start of bevacizumab to death. Progression-free survival (PFS) was defined as the time in months from the start of bevacizumab to progression or death. The time to event variables was estimated using Kaplan Meier method. The median with its 95% confidence interval (CI) was calculated using Brookmeyer and Crowley method. The estimates were compared between the original and bio-similar bevacizumab cohort using the log-rank test. The hazard ratio was calculated using COX regression analysis. Results: There were 82 patients, out of which 57 received innovator and 25 received bio-similar bevacizumab. At median follow up of 26 months, 76 patients had an event for progression. The median PFS was 3.66 (95% CI 2.08 to 5.25) and 3.3 months (95% CI 2.38 to 4.21) in innovator and bio-similar arm respectively (Log-rank test P-value = 0.072). The hazard ratio for progression was 0.61 (95% CI 0.35 to 1.05; P-value = 0.075). At the time of data cutoff, there were 69 deaths. The median OS was 5.53 (95% CI, 5.07 to 5.99) vs 7.33 months (95% CI, 5.63 to 9.03) in innovator and bio-similar arm respectively (Log-rank test P-value = 0.51). The hazard ratio for death was 1.21 (95% CI, 0.67 to 2.17; p-value = 0.51). Conclusions: In the brain tumor patients, both innovator and bio-similar bevacizumab seem to have similar clinical efficacy.


2021 ◽  
Author(s):  
Lang Li ◽  
Qiusheng Guo ◽  
Gaochen Lan ◽  
Fei Liu ◽  
Wenwu Wang ◽  
...  

Abstract Background: Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) tumorigenesis involves a combination of multiple genetic alteration processes. Constructing a survival-associated competing endogenous RNA (ceRNA) network and a multi-mRNA-based prognostic signature model can help us better understand the complexity and genetic characteristics of CESC.Methods: The RNA-seq data and clinical information of CESC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed mRNAs, lncRNAs and miRNAs were identified by edgeR package. Constructing prognostic model used the differentially expressed RNAs. The Kaplan-Meier method and log-rank test were performed to assess survival rates. The relationships between overall survival (OS) and clinical parameters were evaluated by Cox regression analysis. A survival-associated ceRNA network was constructed by multiMiR package and miRcode database. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Ontology (GO) were used to identify the functional role of the ceRNA network in the prognosis of CESC.Results: Differentially expressed 298 mRNAs, 8 miRNAs, and 29 lncRNAs were significantly associated with the prognosis of CESC. The prognostic signature model based on 4 mRNAs (OPN3, DAAM2, HENMT1, and CAVIN3) was constructed. The prognostic ability was 0.726 for this model. Patients in the high-risk group were significantly associated with worse OS. The KEGG pathways were significantly enriched in the TGF-β and Cell adhesion molecules signaling pathways.Conclusion: This study identified several potential prognostic biomarkers to construct a multi-mRNA-based prognostic model for CESC.


2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Andrea Raffaele Munafò ◽  
Annalisa Turco ◽  
Giorgia Benzoni ◽  
Barbara Cattadori ◽  
Carlo Pellegrini ◽  
...  

Abstract Aims Cardiac allograft vasculopathy (CAV) remains the ‘Achilles’ heel’ of successful long-term outcome after heart transplantation (HTx). Percutaneous coronary intervention (PCI) with bare-metal stents (BMS) and first (I) generation drug-eluting stents (DES) has been previously considered as a palliative treatment option in this setting, for the higher rate of restenosis and the lack of a survival benefit over medical therapy. Few data on the performance of second (II) generation DES in CAV are currently available. Our study aims to compare the efficacy and safety of PCI with I and II generation DES in patients with CAV. Methods and results All consecutive heart transplant patients who underwent urgent or elective PCI with I or II generation DES between 2003 and 2020 at Foundation IRCCS Polyclinic San Matteo (Pavia) were enrolled. The extent of revascularization for each patient was assessed calculating the post-procedural residual SYNTAX score. The primary endpoint was a composite of MACE [any myocardial infarction, cardiovascular death and target vessel revascularization (TVR)] at 3-year. The secondary endpoint was target lesion failure (TLF) at 3-year—composite of cardiovascular death, target vessel myocardial infarction (TV-MI) and target lesion revascularization (TLR). A total of 90 transplant patients (113 coronary lesions) were included: 28 patients (32 lesions) were treated with I generation DES and 62 patients (81 lesions) with II generation DES. No differences between the two study groups were identified in term of number of stents per patient implanted (overall 1.63 ± 0.87, P-value = 0.628), total stent length per patient [overall 26 (25th–75th : 18–44) mm, P-value = 0.486], pre-PCI [overall 8 (25th–75th: 5–15), P-value = 0.286], and post-PCI residual [overall 1.5 (25th–75th: 0–4), P-value = 0.187] SYNTAX score. In the whole study population, the primary and secondary endpoints occurred in 28 (33%) and 23 (27%) cases respectively, with a 3-year Kaplan–Meier estimate of freedom from MACE of 64%, and from TLF of 71%. No statistical differences between the two study arms were found (MACE log-rank test P-value = 0.269, TLF log-rank test P-value = 0.260). At multivariate Cox regression analysis, while treatment with II generation DES was confirmed to not predict the risk of MACE (HR: 0.70, CI: 0.32–1.5, P-value = 0.368), a borderline significant higher rate of events was found in patients with a post-PCI residual SYNTAX score >8 (HR: 2.37, CI: 0.98–5.73, P-value = 0.054). However, patients treated with II generation DES experienced a lower rate of TVR (3-year Kaplan-Meier estimate of freedom from TVR I generation DES 69% vs. II generation DES 85%, log-rank test P-value = 0.058, univariate Cox regression analysis HR: 0.4, CI: 0.13–1.07, P-value = 0.069). Conclusions In heart transplant patients with CAV, compared with I generation DES, PCI with II generation DES did not show to reduce the risk of MACE and TLF, guaranteeing however a lower rate of TVR. In this complex clinical scenario, incomplete revascularization (defined as a residual post-PCI SYNTAX score > 8) was associated with worse outcome at 3-year follow-up.


2020 ◽  
Author(s):  
Feng Huang ◽  
Yuanfei Peng ◽  
Qing Ye ◽  
Jinhu Chen ◽  
Yangming Li ◽  
...  

Abstract Background: Cartilage Intermediate Layer Protein 2 (CILP2), a glycoprotein with mutations associated with abnormal blood lipid concentrations in normal and cardiovascular diseases patients, was barely reported with clinical features of tumors. We evaluated the role of CILP2 among all stages and histology in colorectal cancer (CRC) in the Cancer Genome Altas (TCGA), and furtherly verified using immunohistochemistry assay within human CRC tissues. Materials and methods : Clinical information and RNA-seq data were derived from TCGA colorectal carcinoma cohort. CILP2 expression at mRNA level was estimated by bioinformatical analysis of TCGA cases. Tissue microarray (TMA) was constructed containing paraffin-embedded 64 pairs of CRC and matched adjacent normal tissues. The expression at protein level was detected in 64 pairs of CRC and matched adjacent normal tissues by immunohistochemical analysis. CILP2 expression level and its clinical value were estimated by bioinformatical analysis with linear and logistic regression. Survival analysis was performed between high and low groups of CILP2 expression by Cox regression analysis, and P value was calculated by log-rank test. Kaplan-Meier curves were tested by log-rank test. Results : CILP2 was significantly higher expressed in the colorectal cancer tissues when compared with paired adjacent normal tissues in TCGA cohort ( P <0.001) and in TMA cohort ( P =0.001). In addition, CILP2 high-expression was strongly correlated with T3/4 stage ( P =0.001), N1/2/3 stage ( P =0.005), M1 stage ( P =0.048), and higher clinical stage (UICC 2010 stage) ( P <0.001) in TCGA cohort, and also positively associated with T3/4 stage ( P =0.022) and higher clinical stage (UICC 2010 stage) ( P =0.03) in TMA cohort. Furthermore, CILP2 overexpression predicted poor prognosis and could be as an independent prognostic factor ( P =0.003). Conclusion : We revealed that CILP2 is associated with advanced stages and could play a role as an independent predictor of poor survival in colorectal cancer. Key words: CILP2; Colorectal cancer; TCGA; Immunohistochemistry; Prognosis


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Matsushita ◽  
B Marchandot ◽  
M Kibler ◽  
C Sato ◽  
J Heger ◽  
...  

Abstract Introduction Paravalvular leakage (PVL) following transcatheter aortic valve replacement (TAVR) is associated with greater mortality. In clinical practice, determining PVL severity after TAVR remains challenging and often requires multiparametric assessment. Purpose This study sought to evaluate the respective value of various modalities of PVL assessments, including transthoracic echocardiography (TTE), cine-angiography, aortic regurgitation index (ARI), and closure time with adenosine diphosphate (CT-ADP), in the prediction of adverse clinical outcomes. Methods We included 1044 patients from our prospective TAVR registry between February 2010 and May 2019. Major adverse cardiac and cerebrovascular events (MACCE) was defined as a composite of all-cause death, myocardial infarction, stroke, and heart failure hospitalization within 1-year. Established cutoff values of ARI (&lt;25) and CT-ADP (&gt;180 sec) were used to assess the presence of PVL after TAVR. Results Moderate to severe PVL occurred in 14.2% and 5.2% of patients as measured by TTE and angiography. The rate of patients with ARI &lt;25 and CT-ADP &gt;180 sec were 36.5% and 24.9%, respectively. Among the four modalities, PVL evaluated by angiography predicted poorer clinical outcomes (Log rank test; p=0.001), whereas TTE, ARI &lt;25, and CT-ADP &gt;180 sec were not associated with 1-year MACCE. By multivariate Cox regression analysis, moderate to severe PVL by angiography was an independent predictor of 1-year MACCE (hazard ratio: 1.96; 95% confidence interval: 1.22–3.00; p=0.007). Conclusions Paravalvular leakage measured by angiography was evidenced as the most meaningful modality in the prediction of adverse clinical outcomes. Future multicenter studies are warranted to ensure these findings in the current TAVR era. Figure 1 Funding Acknowledgement Type of funding source: None


2021 ◽  
Author(s):  
Chi-hsien Huang ◽  
Ting-Chun Lin ◽  
Ming-Yu Lien ◽  
Fu-Ming Cheng ◽  
Kai-Chiun Li ◽  
...  

Abstract BackgroundAim of this study was to evaluate the prognostic of tumor volume reduction rate (TVRR) status post induction chemotherapy (IC) in LA-HNSCC.MethodsPatients with newly diagnosed LA-HNSCC from year 2007 to 2016 at a single center were included in this retrospective study. All patients had received IC as TPF (taxotere, platinum, fluorouracil) followed by daily definitive intensity-modulated radiotherapy (IMRT) for 70 Gy in 35 fractions concurrent with or without cisplatin-based chemotherapy. Tumor volume reduction rate of the primary tumor (TVRR-T) and lymph node (TVRR-N) was measured and calculated by contrast-enhanced CT images at diagnosis, and one month after final IC cycle, and analyzed though a univariate and multivariate Cox regression model.ResultsNinety patients of the primary cancer sites at hypopharynx (31/90, 34.4%), oropharynx (29/90, 32.2%), oral cavity (19/90, 21.1%) and larynx (11/90, 12.2%) were included in this study, with a median follow-up time interval of 3.9 years. In univariate Cox regression analysis, the TVRR-T as the only variable showed a significant difference for disease-free survival (DFS) (hazard ratio [HR] 0.77, 95% confidence interval (CI) 0.63 to 0.96; P = 0.02), aside from cancer site, RECIST, age and IC dose. In multivariate Cox regression analysis, The TVRR-T was also an independently significant prognostic factor for DFS (HR 0.77, 95% CI 0.62 to 0.97; P = 0.02). At a cutoff value using TVRR-T of 50% in Kaplan-Meier survival analysis, the DFS was significant higher with TVRR-T ≥ 50% group (log-rank test, p = 0.024), and also a trend of improved OS. (log-rank test, p = 0.069).ConclusionsTVRR-T was related to improved DFS and trend of improved OS. Other factors including patient’s age at diagnosis, the primary cancer site, and RECIST, were not significantly related to DFS.


2020 ◽  
Author(s):  
Yue Zhao ◽  
Xiangjun Kong ◽  
Hongbing Wang

Abstract Background: Lung cancer is one of the most common cancers, with high morbidity and mortality. MiRNAs are proved to play important roles in various human cancers. In our study, we aimed to explore the prognostic value of miR-181 in lung cancerMethods: Quantitative real-time polymerase chain reaction (QRT-PCR) was used to detect the expression level of miR-181 in lung cancer tissues and the paired non-cancerous tissues. The relationship between miR-181 expression and clinicopathologic parameters were analyzed by chi-square test. Kaplan-Meier method with log rank test was applied for overall survival analysis. Furthermore, the Cox regression analyses were performed to evaluate the prognostic value of miR-181 in lung cancer.Results: Down-regulated miR-181 expression was observed in lung cancer tissues (P<0.001), moreover, its expression was significantly correlated with TNM stage (P=0.015) and metastasis (P=0.000). In addition, lung cancer patients with lower miR-181 expression level had poorer overall survival than those with higher expression (log rank test, P=0.011). Cox regression analysis suggested that miR-181 was an independent prognostic factor for lung cancer (HR=1.961, 95%CI=1.135-3.388, P=0.016).Conclusion: MiR-181 may be a tumor suppressor gene in lung cancer, which can predict outcomes for the patients.


2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Chao Li ◽  
Wu Yao ◽  
Congcong Zhao ◽  
Guo Yang ◽  
Jingjing Wei ◽  
...  

Background. Esophageal cancer is one of the most deadly malignant tumors. Among the common malignant tumors in the world, esophageal cancer is ranked seventh, which has a high mortality rate. Long noncoding RNAs (lncRNAs) play an important role in the occurrence and development of various tumors. lncRNAs can competitively bind microRNAs (miRNAs) with mRNA, which can regulate the expression level of the encoded gene at the posttranscriptional level. This regulatory mechanism is called the competitive endogenous RNA (ceRNA) hypothesis, and ceRNA has important research value in tumor-related research. However, the regulation of lncRNAs is less studied in the study of esophageal cancer. Methods. The Cancer Genome Atlas (TCGA) database was used to download transcriptome profiling data of esophageal cancer. Gene expression quantification data contains 160 cancer samples and 11 normal samples. These data were used to identify differentially expressed lncRNAs and mRNAs. miRNA expression data includes 185 cancer samples and 13 normal samples. The differentially expressed RNAs were identified using the edgeR package in R software. Then, the miRcode database was used to predict miRNAs that bind to lncRNAs. MiRTarBase, miRDB, and TargetScan databases were used to predict the target genes of miRNAs. Cytoscape software was used to draw ceRNA network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using DAVID 6.8. Finally, multifactor cox regression was used to screen lncRNAs related to prognosis. Results. We have screened 1331 DElncRNAs, 3193 DEmRNAs, and 162 DEmiRNAs. Among them, the ceRNA network contains 111 lncRNAs, 11 miRNAs, and 63 DEmRNAs. Finally, we established a prediction model containing three lncRNAs through multifactor Cox regression analysis. Conclusions. Our research screened out three independent prognostic lncRNAs from the ceRNA network and constructed a risk assessment model. This is helpful to understand the regulatory role of lncRNAs in esophageal cancer.


2020 ◽  
Author(s):  
Zhi-Cheng Liu ◽  
Yan-Qing Li ◽  
Yan Jiao ◽  
Yue-Chen Zhao

Abstract Background: Liver cancer (LC) is a common malignancy with very high morbidity. Pyruvate dehydrogenase kinases (PDKs) are regulators of mitochondrial pyruvate dehydrogenase complexes (PDCs) and play an important role in regulating cellular energy metabolism. In this study, The Cancer Genome Atlas (TCGA) database was used to analyze the expression of PDK2 mRNA in LC, and to explore the value of PDK2 in the diagnosis and prognosis of LC.Methods: The TCGA database, containing the clinical data of 373 LC patients, includes information on PDK2 expression values. The receiver operating characteristic (ROC) curve of PDK2 was drawn to evaluate its diagnostic ability. Patients were divided into PDK2 high- and low-expressing groups by threshold levels. The Chi-square test was used to evaluate the correlation between PDK2 levels and clinicopathological characteristics. The Kaplan-Meier estimator and Cox regression analysis were performed to assess the effect of PDK2 levels on survival outcomes.Results: PDK2 expression in LC tissue was lower than that in normal liver tissues. According to the area under the curve (AUC) value calculated by ROC, PDK2 has a considerable diagnostic value for LC prognosis. The decreased expression of PDK2 is associated with clinical parameters, such as histologic grade ( P =0.0001), radiation therapy ( P =0.0490), vital status ( P =0.0240), and overall survival (OS) ( P =0.0222). Multivariate analysis shows that decreased PDK2 level is an independent risk factor for predicting poor prognosis in LC.Conclusions: PDK2 has a significant impact on the prognosis of LC and is a potential biomarker for the diagnosis and prognosis of LC.


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