Prevalence and Impact of Frailty in Pancreatic Cancer: A Systematic Review and Meta-Analysis Based on 35,191 Patients.

BACKGROUND: Frailty has been associated with increased mortality among patients with pancreatic cancer. Nevertheless, several lines of evidence regarding the prevalence of frailty in patients with pancreatic cancer and mortality in patients with pancreatic cancer and frailty have not been thoroughly investigated and require clarification. METHODS: A systematic review and meta-analysis of studies indexed in PubMed, Scopus, Web of Science, and Embase through March 2023 were conducted, and the pooled prevalence and relative risk (RR) estimate were calculated. RESULTS: A total of 18 studies containing 35,191 patients with pancreatic cancer were included. The prevalence of frailty in pancreatic cancer was 45% (95% CI = 29-62; I2 = 99.9%; p = 0.000). In patients with pancreatic cancer, frailty was associated with increased relative risk for mortality (RR = 1.70; 95% CI = 1.30-2.22; I2 = 84.8%, p = 0.000). CONCLUSIONS: Frailty prevalence in pancreatic cancer is common and exerts a significant negative impact on the survival of patients with pancreatic cancer. Our findings are characterized by significant heterogeneity, and caution is warranted in their interpretation. However, these findings highlight the importance of evaluating frailty, which may provide prognostic data and inform decision-making priorities.

Identification of the Immune Subtypes for the Prediction of Metastasis in Pancreatic Neuroendocrine Tumors.

INTRODUCTION: Most patients with pancreatic neuroendocrine tumors (pNETs) present with unresectable or metastatic disease. Increasing evidence shows that the immune cell infiltration patterns play a pivotal role in tumor progression in pNETs. Nonetheless, there has been no comprehensive analysis of the effect of immune infiltration patterns on metastasis. METHODS: The gene expression profiling dataset and clinical data were obtained from the Gene Expression Omnibus database. Estimation of Stromal and Immune Cells in Malignant Tumors using the Expression Data and single-sample Gene Set Enrichment Analysis were used to uncover the landscape of the tumor immune microenvironment. Subtypes based on the immune infiltration patterns were identified by the unsupervised clustering algorithm. Differentially expressed genes were identified using the limma packages of R. Functional enrichment analyses of these genes were carried out using STRING, Kyoto Encyclopedia of Genes and Genomes, and Reactome. RESULTS: The landscape of immune cells in pNET samples was constructed, and three immune cell infiltration subtypes (Immunity-H, Immunity-M, and Immunity-L) were identified. Immune cell infiltration degrees and metastasis were positively correlated. A protein-protein interaction network containing 80 genes was constructed, and functional enrichment revealed that these genes were mainly enriched in immune-related pathways. Eleven metastasis-related genes were differentially expressed among three subtypes, including MMP14, MMP2, MMP12, MMP7, SPARC, MMP19, ITGAV, MMP23B, MMP1, MMP25, and MMP9. There is a certain consistency of immune infiltration pattern between the primary tumor and metastatic tumor samples. CONCLUSION: Our findings may deepen the understanding of the immune-mediated regulatory mechanisms underlying pNETs and may provide some promising targets for immunotherapy.

Sufentanil ameliorates oxygen-glucose deprivation/reoxygenation-induced endothelial barrier dysfunction in HCMECs via the PI3K/Akt signaling pathway.

Ischemic heart disease, a chronic myocardial damage disease caused by coronary artery ischemia, is the leading cause of death worldwide. The aim of the present study was to explore the efficacy of sufentanil in myocardial ischemia/reperfusion (I/R) injury. Oxygen and glucose deprivation/reoxygenation (OGD/R) was utilized to induce human cardiac microvascular endothelial cells (HCMECs) to simulate myocardial I/R injury in vitro. The Cell Counting Kit-8 assay was used to detect the effects of sufentanil on HCMECs and OGD/R-induced HCMECs. The TUNEL, lactate dehydrogenase (LDH) activity, immunofluorescence and in vitro permeability assays, were used to assess apoptosis, LDH activity, VE-cadherin protein expression levels and endothelial barrier function in OGD/R-induced HCMECs, respectively. Moreover, western blotting was performed to assess the protein expression levels of apoptosis, endothelial barrier function and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)-related proteins. The results demonstrated that sufentanil had no significant influence on the viability of HCMECs but increased the viability of OGD/R-induced HCMECs in a dose-dependent manner. Furthermore, sufentanil inhibited cell apoptosis and permeability of OGD/R-induced HCMECs but enhanced the protein expression levels of tight junction proteins, including ZO-1, Occludin, VE-cadherin and Claudin-5. Sufentanil was also demonstrated to activate the PI3K/Akt signaling pathway. In addition, the use of LY294002, an inhibitor of the PI3K/Akt signaling pathway, partially abolished the protective effects of sufentanil on apoptosis, permeability and tight junction protein expression levels. These results indicated that sufentanil ameliorated OGD/R-induced endothelial barrier dysfunction in HCMECs, potentially via the PI3K/Akt signaling pathway. The present study therefore suggested that sufentanil may serve as a novel therapeutic option for the improvement of myocardial I/R injury.

One-lung ventilation patients: Clinical context of administration of different doses of dexmedetomidine.

Background: Open and endoscopic thoracic surgeries improve surgical exposure by One-lung ventilation (OLV). The aim of this study was to investigate the effects of different doses of dexmedetomidine on inflammatory response, oxidative stress, cerebral tissue oxygen saturation (SctO2) and intrapulmonary shunt in patients undergoing one-lung ventilation (OLV). Methods: Seventy-five patients undergoing open pulmonary lobectomy in our hospital from January 2016 to December 2017 were enrolled and randomly divided into high-dose dexmedetomidine group (group D1, 1 mg/kg, n=25), low-dose dexmedetomidine group (group D2, 0.5 mg/kg, n=25) and control group (group C, n=25). Then, arterial blood and internal jugular venous blood were taken before anesthesia induction (T0) and at 15 min after twolung ventilation (T1) and 5 min (T2) and 30 min (T3) after OLV for later use. Next, the changes in hemodynamic parameters [mean arterial pressure (MAP), heart rate (HR) and pulse oxygen saturation (SpO2)] of patients were observed in each group. Enzyme-linked immunosorbent assay (ELISA) was carried out to detect serum inflammatory factors such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) and oxidative stress indicators [superoxide dismutase (SOD) and malondialdehyde (MDA)]. The changes in SctO2, arterial partial pressure of oxygen (PaO2) and intrapulmonary shunt Qs/Qt (a measurement of pulmonary shunt: right-to-left shunt fraction) were observed. Additionally, the changes in lung function indicators like lung dynamic compliance (Cdyn) and airway peak pressure (Ppeak) were determined. Results: There were no statistically significant differences in the MAP, HR and SpO2 among three groups at each observation time point (P>0.05). At T2 and T3, the levels of serum IL-6, TNF-α and IL-8 were obviously decreased in group D1 and D2 compared with those in group C (P<0.05), and the decreases in group D1 were overtly larger than those in group D2, and the decreases at T3 were markedly greater than those at T2 (P<0.05). In comparison with group C, group D1 and D2 had notably reduced levels of serum reactive oxygen species (ROS) and MDA (P<0.05) and remarkably increased SOD content (P<0.05) at T2 and T3, and the effects were markedly better in group D1 than those in group D2. Besides, they were significantly superior at T3 to those at T2 (P<0.05). The SctO2 in group D1 and D2 was evidently lowered at T2 and T3 compared with that at T0, and the decrease in group D1 was distinctly smaller than that in group D2 (P<0.05). The Qs/Qt was significantly lower in group D1 and D2 than that in group C at T2 and T3 (P<0.05), while the PaO2 content was notably raised (P<0.05), and the decrease and increase were significantly larger in group D1 than those in group D2, and they were obviously greater at T3 to those at T2 (P<0.05). At T0 and T1, no significant differences were detected in the Cdyn, Pplat and Ppeak among three groups. At T2 and T3, the Cdyn was significantly elevated, while the Pplat and Ppeak overtly declined (P<0.05), and group D1 had greater changes in comparison with group D2, and the changes were obviously more evident at T3 to those at T2 (P<0.05). Conclusions: Dexmedetomidine effectively ameliorates inflammatory response and oxidative stress, lowers oxygenation, Qs/Qt and the decrease in SctO2 and improves lung function during OLV, with good efficacy.

High expression of LAMA3/AC245041.2 gene pair associated with KRAS mutation and poor survival in pancreatic adenocarcinoma: a comprehensive TCGA analysis.

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is one of the most challenging cancers with high morbidity and mortality. KRAS mutations could occur as an early event in PAAD. The present study aimed to identify the differentially expressed lncRNAs (DE-lncRNAs) and differentially expressed mRNAs (DE-mRNAs) in KRAS-mutant PAAD to explore the pathogenesis and the underlying molecular mechanism of PAAD development. METHODS: Clinical data of TCGA-PAAD patients were downloaded from the TCGA database and subjected to survival analysis along with the KRAS mutation information data. Weighted gene correlation network analysis (WGCNA) and univariate Cox regression analysis were conducted to construct prognostic risk models to identify the hub DE-mRNAs and DE-lncRNAs associated with PAAD prognosis. GO and KEGG enrichment analyses of the identified hub DE-mRNAs were performed. Multivariate cox regression analysis was performed to analyze the overall prognosis of age, gender, pathologic_T, and KRAS mutations, following which the differences in the clinical characteristics of risk score1 and risk score2 were analyzed. Finally, the mRNAs-lncRNA-TFs regulatory network was constructed. RESULTS: Functional enrichment analysis was performed after screening 1671 DE-mRNAs and 324 DE-lncRNAs. It was observed that the associated pathways were enriched mainly in the modulation of chemical synaptic transmission, synaptic membrane, ion-gated channel activity, ligand-receptor interactions that stimulate neural tissue, among others. The univariate Cox regression analysis screened 117 mRNAs and 36 lncRNAs, and the risk ratio models of the mRNAs and lncRNAs were constructed. LAMA3 (mRNA) and AC245041.2 (lncRNA) exhibited a strong expression correlation in the respective two risk models. The genes in the samples with a high expression of these two genes were enriched in several pathways associated with transcription factors (TFs), among which the TFs ATF5, CSHL1, NR1I2, SIPA1, HOXC13, HSF2, and HOXA10 were shared by the two groups. The core enrichment genes in the common TF pathways were collated, and the mRNAs-lncRNAs-TFs regulatory network was constructed. CONCLUSION: In the present study, novel prognostic mRNAs and lncRNAs were identified, and their respective prognostic models and nomograms were constructed to guide clinical practice. An mRNAs-lncRNAs-TFs regulatory network was also constructed, which could assist further research in the future.

Different anaesthesia methods affect the development of hepatoblastoma after platelet activation.

This study aims to compare the influence of different anaesthesia methods on the mechanisms involved in the development of hepatoblastoma (HB). HB rabbit models were constructed and divided into three groups: disoprofol, pentobarbital sodium and HB groups. After anaesthesia, rabbit blood was collected from the tail vein. Haematological analysis (platelets) and an ELISA was used to measure the thrombopoietin (TPO) and 5-hydroxytryptamine (5-HT). Flow cytometry was used to determine expression of P-selectin and PAF. The expression of 5-HTR2B, PCNA, vWF, P70s6k, 4E-BP1, mTOR and FRAP was determined in the tumour itself or in vascular tissues obtained from the rabbits. The platelet content in the disoprofol group. The content or expression of TPO, 5-HT, P-selectin, PAF, 5-HTR2B, PCNA, vWF, P70s6k, 4E-BP1, mTOR and FRAP was significantly higher in the disoprofol group compared to pentobarbital sodium and HB groups. Expression of these molecules was much higher in the pentobarbital sodium group compared with the HB group. These findings suggest that disoprofol anaesthesia can promote HB development via the mTOR/p70S6K1 and FRAP signalling pathway.

A transcriptome profile in gallbladder cancer based on annotation analysis of microarray studies.

The purpose of the present study was to identify aberrantly expressed genes for gallbladder cancer based on the annotation analysis of microarray studies and to explore their potential functions. Differential gene expression was investigated in cholesterol polyps, gallbladder adenoma and gallbladder cancer using microarrays. Subsequently, microarray results were comprehensively analyzed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to determine the affected biological processes or pathways. Differentially expressed genes (DEGs) of cholesterol polyps, gallbladder adenoma and gallbladder cancer were identified. Following comprehensive analysis, 14 genes were found to be differentially expressed in the gallbladder wall of both gallbladder cancer and gallbladder adenoma. The 20 most significantly upregulated genes were only upregulated in the gallbladder wall of gallbladder cancer, but not in the gallbladder wall of cholesterol polyps and gallbladder adenoma. In addition, 182 DEGs were upregulated in the gallbladder wall of gallbladder adenoma compared with the gallbladder wall of cholesterol polyps. A total of 20 most significant DEGs were found in both the tumor and gallbladder wall of gallbladder cancer. In addition, the most significant DEGs that were identified were only upregulated in the tumor of gallbladder cancer. GO and KEGG analysis indicated that the aforementioned DEGs could participate in numerous biological processes or pathways associated with the development of gallbladder cancer. The present findings will help improve the current understanding of tumorigenesis and the development of gallbladder cancer.

LncRNA C9orf139 can regulate the growth of pancreatic cancer by mediating the miR-663a/Sox12 axis.

BACKGROUND: Recent studies have proved the important role of many oncogenic long non-coding RNAs (lncRNAs) in the progression of pancreatic cancer, but little is known about the mechanisms of tumor suppression in pancreatic cancer. AIM: To evaluate the function of tumor suppressor lncRNA C9orf139 in pancreatic cancer progression and to study the underlying mechanism. METHODS: We assigned 54 patients with pancreatic ductal adenocarcinoma treated at our hospital to the patient group and 30 normal subjects undergoing physical examination to the control group. RT-qPCR was used to measure the relative expression of C9orf139 in the tissue and serum of patients, in an attempt to investigate the prognostic value of C9orf139 in pancreatic cancer patients. The luciferase reporter gene assay was performed to determine the interaction between C9orf139 and miR-663a. The biological function of C9orf139 was assessed by in vitro assays and in vivo subcutaneous tumor formation tests in animal models. To figure out the molecular mechanism of C9orf139 to act on miR-663a/Sox12, RNA pull-down, Western blot assay, RNA immunoprecipitation assay, and co-immunoprecipitation assay were performed. RESULTS: C9orf139 level significantly increased in the tissue and serum of patients, which had clinical diagnostic value for pancreatic cancer. Patients with high C9orf139 expression had a higher risk of progressing to stage III + IV, lymph node metastasis, and poor differentiation. Cox regression analysis suggested that C9orf139, tumor-node-metastasis stage, and lymph node metastasis were independent prognostic factors in patients. The underlying mechanism of C9orf139 was that it promoted the growth of pancreatic cancer cells by modulating the miR-663a/Sox12 axis. CONCLUSION: C9orf139 is highly expressed in pancreatic cancer, qualified to be used as a potential diagnostic and prognostic marker for pancreatic cancer. Its promotion of pancreatic cancer cell growth is achieved by mediating the miR-663a/Sox12 axis.

Erratum: Identification of UBE2T as an independent prognostic biomarker for gallbladder cancer.

[This corrects the article DOI: 10.3892/ol.2020.11903.].

Mapping Intellectual Structure and Research Performance for the Nanoparticles in Pancreatic Cancer Field.

OBJECTIVE: To comprehensively analyze the global scientific outputs of nanoparticles in pancreatic cancer research. METHODS: Publications regarding the nanoparticles in pancreatic cancer research published from 1986 to 2019 were retrieved from the Web of Science Core Collection (WoSCC). Highly frequent keywords, publication years, journals, cited papers, cited journals and cited authors were identified using BICOMB software, and then a binary matrix and a co-word matrix were constructed. gCLUTO was used for double clustering of highly frequent journals. Co-citation analysis was performed using CiteSpace V software, including keywords, references, journals author or institution cooperation network. RESULTS: A total of 1171 publications were included in this study. Publications mainly came from 10 countries, led by the US (n=470) and China (n=349). Among the top 20 journals ranked by the number of citations, nanoscience nanotechnology was the leader with 300. Cluster analysis of citation network identified 12 co-citation clusters, headed by "stromal barrier" and "emerging inorganic nanomaterial". CONCLUSION: Our findings reveal the research performance and intellectual structure of the nanoparticles in pancreatic cancer research, which may help researchers understand the research trends and hotspots in this field.

Identification of UBE2T as an independent prognostic biomarker for gallbladder cancer.

Gallbladder cancer is the most common biliary tract malignant tumor, with unfavorable patient outcomes. The present study aimed to identify potential diagnostic or prognostic biomarkers for gallbladder cancer. To do so, differentially expressed genes in the gallbladder walls and tumor tissues of patients with gallbladder cancer were analyzed via microarray. Furthermore, a protein-protein interaction network was constructed and genes with a degree score >10 were selected as hub genes. As ubiquitin conjugating enzyme E2T (UBE2T) was considered to be a hub gene, its expression was assessed via reverse transcription-quantitative (RT-q)PCR and immunohistochemistry (IHC). In addition, the association between UBE2T expression and the clinicopathological characteristics of patients with gallbladder cancer was analyzed using the χ2 test. Furthermore, all patients were divided into high- and low groups based on UBE2T expression level and overall survival analysis was performed. Univariate and multivariate Cox regression analyses were performed to determine whether UBE2T may serve as an independent risk factor for gallbladder cancer. The results demonstrated that UBE2T expression was upregulated in the gallbladder walls and tumor tissues of patients with gallbladder cancer. Furthermore, UBE2T expression level was confirmed to be upregulated following RT-qPCR, and results from IHC demonstrated that UBE2T was predominantly expressed in the cytoplasm of gallbladder cancer cells. In addition, high UBE2T expression level was associated with clinical stage, T classification, N classification and M classification. The results from Univariate and multivariate analyses indicated that UBE2T expression level may be considered as an independent risk factor for gallbladder cancer. Taken together, the findings from this study suggested that high UBE2T expression level may contribute to the poor prognosis of patients with gallbladder cancer, and that UBE2T may act as an independent prognostic biomarker for these patients.

Effect of CEACAM6 silencing on the biological behavior of human gallbladder cancer cells.

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is abnormally expressed in various malignant tumors and thus represents a potential biomarker, although information regarding its role in gallbladder cancer (GBC) is limited. This study aimed to evaluate the expression of CEACAM6 in GBC and the effect of CEACAM6 gene silencing on the proliferation, migration, invasion and apoptosis of human GBC cells. Immunochemistry was used to evaluate CEACAM6 expression in 95 GBC specimens and 40 peritumoral tissue specimens. GBC-SD and SGC-996 cell lines were used for in vitro experiments. CEACAM6 was knocked down by transfection of targeted small interfering RNA (siRNA), and reverse-transcription quantitative PCR and western blot analysis were used to detect knockdown efficiency. Cell Counting Kit-8 and colony formation assays were undertaken to evaluate cell proliferation. Variations in cell migration and invasion were detected by wound-healing and Transwell assays, respectively. Flow cytometry was applied to measure cell apoptosis and cell cycle distribution. CEACAM6 gene expression was significantly greater in GBC tissues than in peritumoral tissues, and its positive expression was associated with poor prognosis. CEACAM6 mRNA and protein expression in the CEACAM6 siRNA treatment group was significantly lower than that in the negative control group and the blank group. CEACAM6 knockdown inhibited GBC cell proliferation, migration and invasion but promoted cell apoptosis. Western blot analysis of invasion- and apoptosis-related proteins matrix metalloproteinase-2, Vimentin, BCL-2 and BAX further confirmed CEACAM6 mRNA depletion promoted cell apoptosis and inhibited invasion. Additionally, CEACAM6 mRNA depletion affected the progression of the GBC cell cycle to increase cell distribution in G0/G1 phase, and to reduce it in G2/M phase and S phase. These findings indicated that CEACAM6 overexpression may be related to the tumorigenesis and development of GBC. In summary, depletion of CEACAM6 mRNA suppressed the malignant biological behaviors of human gallbladder cancer cells.

Propofol suppresses hepatocellular carcinoma by inhibiting NET1 through downregulating ERK/VEGF signaling pathway.

Hepatocellular carcinoma (HCC) is the leading cause of tumor death in China with high mortality since its strong metastatic potential. Currently, treatment against advanced HCC is poorly efficient and thus screening new drugs to prevent the HCC invasion is of great significance to improve the survival rate of patients with HCC. From the results of this study, we concluded that propofol, a widely used anesthetics could prevent the proliferation by MTT assay. The scratch wound and invasion assays showed that migratory property and invasiveness in HCC cells SMMC-7721 was inhibited by propofol. This process was probably mediated by NET1 since NET1 overexpression offset the repressive effect of propofol on the invasiveness and migratory ability of SMMC-7721 cells. Furthermore, propofol treatment also reduced p-ERK1/2 and VEGF level by western blot analysis. Similar observation was found when NET1 was silenced. Thus, the results of this study provided valuable clinical therapy potential of propofol against liver cancer. We also disclosed molecular mechanism underlying the regulation of invasion and migration in HCC cells by NET1.

LncRNA ZFAS1 promotes pancreatic adenocarcinoma metastasis via the RHOA/ROCK2 pathway by sponging miR-3924.

BACKGROUND: The mortality and morbidity rates of pancreatic adenocarcinoma have been increasing over the past two decades, and an understanding of the mechanisms underlying pancreatic adenocarcinoma progression is urgently needed. The long non-coding RNA ZFAS1 has been demonstrated to be an oncogene in some cancers, but its function and mechanism in pancreatic adenocarcinoma remain unclear. METHODS: The ZFAS1 expression level in pancreatic adenocarcinoma was predicted by bioinformatic analysis, and the expression level of ZFAS1 in pancreatic adenocarcinoma tissue samples and cell lines was further detected by quantitative real-time PCR and in situ hybridization. The functions of ZFAS1 in pancreatic adenocarcinoma in vitro and in vivo were investigated by further bioinformatic analysis. Dual-luciferase reporter assays were used to confirm the binding of ZFAS1/miR-3924 and miR-3924/ROCK2, and rescue assays were performed to further investigate the underlying mechanism. RESULTS: ZFAS1 overexpression in pancreatic adenocarcinoma was predicted and experimentally verified. ZFAS1 silencing inhibited pancreatic adenocarcinoma metastasis in vitro and in vivo. The competing endogenous RNA mechanism of ZFAS1 was also identified. CONCLUSIONS: Our results demonstrated the promotive effect of ZFAS1 on pancreatic adenocarcinoma metastasis and suggested its potential role as a novel regulator of ROCK2.

Elevated hsa_circRNA_101015, hsa_circRNA_101211, and hsa_circRNA_103470 in the Human Blood: Novel Biomarkers to Early Diagnose Acute Pancreatitis.

OBJECTIVE: To explore potential biomarkers to accurately diagnose patients with acute pancreatitis (AP) at early stage and to auxiliary clinicians implement the best treatment options. METHODS: We selected 3 patients with AP and 3 healthy controls for microarray analysis to obtain differentially expressed circular RNAs (circRNAs). To further verify the results of the microarray analysis, the six differentially expressed circRNAs were confirmed by quantitative polymerase chain reaction (qPCR). The diagnostic accuracy and sensitivity of differentially expressed circRNAs were assessed using the receiver operating characteristic (ROC) curve. A ceRNA network was constructed based on the 6 differentially expressed circRNAs. RESULTS: There were 25 upregulated circRNAs and 26 downregulated circRNAs in the blood of patients with AP. Next, the qPCR verification results further confirmed three downregulated circRNAs, including hsa_circRNA_002532, has_circRNA_059665, and hsa_circRNA_104156, and three upregulated circRNAs including hsa_circRNA_101015, hsa_circRNA_101211, and hsa_circRNA_103470. Among them, hsa_circRNA_101015, hsa_circRNA_101211, and hsa_circRNA_103470 increased with the severity of the disease. ROC analysis showed that the three circRNA models show promise to diagnose AP. And a ceRNA network revealed that above six circRNAs could participate in complex regulated network. CONCLUSIONS: Elevated hsa_circRNA_101015, hsa_circRNA_101211, and hsa_circRNA_103470 could be used as novel biomarkers to diagnose AP patients.

A Simple Competing Endogenous RNA Network Identifies Novel mRNA, miRNA, and lncRNA Markers in Human Cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CCA) is the second most common malignant primary liver tumor and has shown an alarming increase in incidence over the last two decades. However, the mechanisms behind tumorigenesis and progression remain insufficient. The present study aimed to uncover the underlying regulatory mechanism on CCA and find novel biomarkers for the disease prognosis. METHOD: The RNA-sequencing (RNA-seq) datasets of lncRNAs, miRNAs, and mRNAs in CCA as well as relevant clinical information were obtained from the Cancer Genome Atlas (TCGA) database. After pretreatment, differentially expressed RNAs (DERNAs) were identified and further interrogated for their correlations with clinical information. Prognostic RNAs were selected using univariate Cox regression. Then, a ceRNA network was constructed based on these RNAs. RESULTS: We identified a total of five prognostic DEmiRNAs, 63 DElncRNAs, and 90 DEmRNAs between CCA and matched normal tissues. Integrating the relationship between the different types of RNAs, an lncRNA-miRNA-mRNA network was established and included 28 molecules and 47 interactions. Screened prognostic RNAs involved in the ceRNA network included 3 miRNAs (hsa-mir-1295b, hsa-mir-33b, and hsa-mir-6715a), 7 lncRNAs (ENSG00000271133, ENSG00000233834, ENSG00000276791, ENSG00000241155, COL18A1-AS1, ENSG00000274737, and ENSG00000235052), and 18 mRNAs (ANO9, FUT4, MLLT3, ABCA3, FSCN2, GRID2IP, NCK2, MACC1, SLC35E4, ST14, SH2D3A, MOB3B, ACTL10, RAB36, ATP1B3, MST1R, SEMA6A, and SEL1L3). CONCLUSIONS: Our study identified novel prognostic makers and predicted a previously unknown ceRNA regulatory network in CCA and may provide novel insight into a further understanding of lncRNA-mediated ceRNA regulatory mechanisms in CCA.