scholarly journals Identification of prognostic factors for intrahepatic cholangiocarcinoma using long non-coding RNAs-associated ceRNA network

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhichen Kang ◽  
Lixin Guo ◽  
Zhuo Zhu ◽  
Rongfeng Qu
2020 ◽  
Author(s):  
Zhichen Kang ◽  
Lixin Guo ◽  
Zhuo Zhu ◽  
Rongfeng Qu

Abstract Background: Accumulating amount of evidence has highlighted the important roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in tumor pathogenesis. However, the roles of long non coding RNAs (lncRNAs) in the lncRNA-related ceRNA network of intrahepatic cholangiocarcinoma (ICC) still remain enigmatic. The current study aims to identify prognostic factors in the lncRNA-related ceRNA network of ICC.Methods: The transcriptome sequencing data of lncRNAs, messenger RNA (mRNA) and microRNA (miR) were downloaded from the SRA and TCGA databases. Differentially expressed lncRNAs (DElncRNAs), DEmiRs and DEmRNAs were identified and adopted to construct an lncRNA-miR-mRNA ceRNA network. ICC-associated DEmRNAs were adopted to construct the protein-protein interaction (PPI) network. The expression of the top 6 genes in the hub module was validated with mRNA transcriptome sequencing data and ICC-related gene expression dataset GSE45001, followed by GO and KEGG pathway enrichment analysis. The relationship between the hub gene-associated ceRNA network and the overall survival of patients with ICC was predicted by conducting a Kaplan-Meier survival analysis. Results: Sixty co-expressed DEmRNAs were identified in the ceRNA network. The top 6 hub genes consisted of downregulated FOS, IGF2, FOXO1 and NTF3, upregulated IGF1R, and insignificantly downregulated HGF in ICC tissues, when compared to that of normal adjacent tissues, followed by the successful construction of lncRNA-miR-hub network consisting of 86 ceRNA modules. MME-AS1 and hsa-miR-182 were associated with overall survival in ICC patients. FOS, IGF1R, IGF2, FOXO1, and NTF3 might target “TGF-β signaling pathway”, “the hedgehog signaling pathway”, “retinol metabolism”, or “type II diabetes mellitus” pathways respectively. Conclusion: These results indicate that FOS, IGF1R, IGF2, FOXO1, and NTF3 were useful prognostic factors in determining the prognosis of patients with ICC.


2020 ◽  
Author(s):  
Zhichen Kang ◽  
Lixin Guo ◽  
Zhuo Zhu ◽  
Rongfeng Qu

Abstract Background Accumulating evidence has highlighted the important roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in tumor biology. However, the roles of cancer long non coding RNAs (lncRNAs) in lncRNA-related ceRNA network of intrahepatic cholangiocarcinoma (ICC) remain enigmatic. The current study aims to identify prognostic factors in the lncRNA-related ceRNA network of ICC. Methods The transcriptome sequencing data of the lncRNAs, messenger RNA (mRNA) and microRNA (miR) were downloaded from SRA, and TCGA database respectively. Differentially expressed lncRNAs (DElncRNAs), DEmiRs and DEmRNAs were identified and adopted to construct lncRNA-miR-mRNA ceRNA network. ICC-associated DEmRNAs were adopted to construct the PPI network. The expression of the top 6 genes in the hub module was validated in mRNA transcriptome sequencing data and ICC-related gene expression dataset GSE45001, followed by GO and KEGG pathway enrichment analysis. The potential function of genes in hub module in the ceRNA network was finally subjected to GSEA. Results Sixty coexpression DEmRNAs were identified in the ceRNA network. The 6 top genes in the hub module consists of FOS, HGF, IGF2, FOXO1, NTF3 (downregulated), and IGF1R (upregulated) in ICC tissues compared to normal adjacent tissues, followed by the successful construction of lncRNA-miR-hub network with 86 ceRNA modules. FOS, IGF2 or IGF1R might regulate the development of ICC by targeting “N-glycan biosynthesis”, “α-linolenic acid metabolism” or “type II diabetes” pathways respectively. Conclusion These results show FOS, IGF2 and IGF1R serve as prognostic factors of ICC patients.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wenjie Chen ◽  
Wen Li ◽  
Zhenkun Liu ◽  
Guangzhi Ma ◽  
Yunfu Deng ◽  
...  

AbstractTo identify the prognostic biomarker of the competitive endogenous RNA (ceRNA) and explore the tumor infiltrating immune cells (TIICs) which might be the potential prognostic factors in lung adenocarcinoma. In addition, we also try to explain the crosstalk between the ceRNA and TIICs to explore the molecular mechanisms involved in lung adenocarcinoma. The transcriptome data of lung adenocarcinoma were obtained from The Cancer Genome Atlas (TCGA) database, and the hypergeometric correlation of the differently expressed miRNA-lncRNA and miRNA-mRNA were analyzed based on the starBase. In addition, the Kaplan–Meier survival and Cox regression model analysis were used to identify the prognostic ceRNA network and TIICs. Correlation analysis was performed to analysis the correlation between the ceRNA network and TIICs. In the differently expressed RNAs between tumor and normal tissue, a total of 190 miRNAs, 224 lncRNAs and 3024 mRNAs were detected, and the constructed ceRNA network contained 5 lncRNAs, 92 mRNAs and 10 miRNAs. Then, six prognostic RNAs (FKBP3, GPI, LOXL2, IL22RA1, GPR37, and has-miR-148a-3p) were viewed as the key members for constructing the prognostic prediction model in the ceRNA network, and three kinds of TIICs (Monocytes, Macrophages M1, activated mast cells) were identified to be significantly related with the prognosis in lung adenocarcinoma. Correlation analysis suggested that the FKBP3 was associated with Monocytes and Macrophages M1, and the GPI was obviously related with Monocytes and Macrophages M1. Besides, the LOXL2 was associated with Monocytes and Activated mast cells, and the IL22RA1 was significantly associated with Monocytes and Macrophages M1, while the GPR37 and Macrophages M1 was closely related. The constructed ceRNA network and identified Monocytes, Macrophages M1 and activated Mast cells are all prognostic factors for lung adenocarcinoma. Moreover, the crosstalk between the ceRNA network and TIICs might be a potential molecular mechanism involved.


2018 ◽  
Vol 19 (10) ◽  
pp. 3263 ◽  
Author(s):  
Xiaoyu Wang ◽  
Kaifan Bao ◽  
Peng Wu ◽  
Xi Yu ◽  
Can Wang ◽  
...  

Atopic dermatitis (AD) is a prevalent inflammatory skin disease characterized by its chronic nature and relapse. Ample evidence suggests that non-coding RNAs play a major role in AD pathogenesis. However, the mechanism remains unknown, particularly in AD recurrence. Dynamic morphological and cytokine changes were measured throughout the whole course of an FITC-induced AD recurrence murine model. Microarray assay and integrative analysis were performed to comprehensively explore long non-coding RNA (lncRNA), messenger RNA (mRNA), and microRNA (miRNA) networks. Our results showed that an AD recurrence model was established. Overall, 5766 lncRNAs, 4025 mRNAs, and 202 miRNAs changed after elicitation, whereas, 419 lncRNAs, 349 mRNAs, and more notably, only 23 miRNAs, were dysregulated in the remission phase. Gene ontology (GO) and KEGG pathway enrichment analyses were used to investigate the potential functions of the dysregulated genes. The altered regulation of seven miRNAs and seven lncRNAs were validated in different stages of the model. The competing endogenous RNA (ceRNA) network inferred that lncRNA humanlincRNA0490+ could compete for miR-155-5p binding, through which it might affect Pkiα expression. Altogether, our findings have provided a novel perspective on the potential roles of non-coding RNAs in AD, and suggest that specific non-coding RNAs could be new therapeutic targets against AD recurrence.


2017 ◽  
Vol Volume 10 ◽  
pp. 1441-1449 ◽  
Author(s):  
Chenyue Zhang ◽  
Haiyong Wang ◽  
Zhouyu Ning ◽  
Litao Xu ◽  
Liping Zhuang ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
pp. 56 ◽  
Author(s):  
Michael Köhler ◽  
Fabian Harders ◽  
Fabian Lohöfer ◽  
Philipp M. Paprottka ◽  
Benedikt M. Schaarschmidt ◽  
...  

Purpose: To evaluate factors associated with survival following transarterial 90Y (yttrium) radioembolization (TARE) in patients with advanced intrahepatic cholangiocarcinoma (ICC). Methods: This retrospective multicenter study analyzed the outcome of three tertiary care cancer centers in patients with advanced ICC following resin microsphere TARE. Patients were included either after failed previous anticancer therapy, including relapse after surgical resection, or for having a minimum of 25% of total liver volume affected by ICC. Patients were stratified and response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria at 3 months. Kaplan–Meier analysis was performed to analyze survival followed by cox regression to determine independent prognostic factors for survival. Results: 46 patients were included (19 male, 27 female), median age 62.5 years (range 29–88 years). A total of 65% of patients had undergone previous therapy, while 63% had a tumor volume > 25% of the entire liver volume. Median survival was 9.5 months (95% CI: 6.1–12.9 months). Due to loss in follow-up, n = 37 patients were included in the survival analysis. Cox regression revealed the extent of liver disease to one or both liver lobes being associated with survival, irrespective of tumor volume (p = 0.041). Patients with previous surgical resection of ICC had significantly decreased survival (3.9 vs. 12.8 months, p = 0.002). No case of radiation-induced liver disease was observed. Discussion: Survival after 90Y TARE in patients with advanced ICC primarily depends on disease extent. Only limited prognostic factors are associated with a general poor overall survival.


2019 ◽  
Vol 27 (4) ◽  
pp. 1147-1155 ◽  
Author(s):  
Andreas A. Schnitzbauer ◽  
Johannes Eberhard ◽  
Fabian Bartsch ◽  
Stefan M. Brunner ◽  
Güralp O. Ceyhan ◽  
...  

2020 ◽  
Vol 405 (7) ◽  
pp. 977-988
Author(s):  
Oliver Beetz ◽  
Clara A. Weigle ◽  
Sebastian Cammann ◽  
Florian W. R. Vondran ◽  
Kai Timrott ◽  
...  

Abstract Purpose The incidence of intrahepatic cholangiocarcinoma is increasing worldwide. Despite advances in surgical and non-surgical treatment, reported outcomes are still poor and surgical resection remains to be the only chance for long-term survival of affected patients. The identification and validation of prognostic factors and scores, such as the recently introduced resection severity index, for postoperative morbidity and mortality are essential to facilitate optimal therapeutic regimens. Methods This is a retrospective analysis of 269 patients undergoing resection of histologically confirmed intrahepatic cholangiocarcinoma between February 1996 and September 2018 at a tertiary referral center for hepatobiliary surgery. Regression analyses were performed to evaluate potential prognostic factors, including the resection severity index. Results Median postoperative follow-up time was 22.93 (0.10–234.39) months. Severe postoperative complications (≥ Clavien-Dindo grade III) were observed in 94 (34.9%) patients. The body mass index (p = 0.035), the resection severity index (ASAT in U/l divided by Quick in % multiplied by the extent of liver resection graded in points; p = 0.006), additional hilar bile duct resection (p = 0.005), and number of packed red blood cells transfused during operation (p = 0.036) were independent risk factors for the onset of severe postoperative complications. Median Kaplan-Meier survival after resection was 27.63 months. Preoperative leukocytosis (p = 0.003), the resection severity index (p = 0.005), multivisceral resection (p = 0.001), and T stage ≥ 3 (p = 0.013) were identified as independent risk factors for survival. Conclusion Preoperative leukocytosis and the resection severity index are useful variables for preoperative risk stratification since they were identified as significant predictors for postoperative morbidity and mortality, respectively.


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