Abstract
Pancreatic adenocarcinoma (PAAD) is a pancreatic disease with considerable mortality worldwide. Because of a lack of obvious symptoms at the early stage, most PAAD patients are diagnosed at the terminal stage and prognosis is usually poor. In this study, we firstly obtained RNA sequencing data of 181 patients with PAAD from The Cancer Genome Atlas (TCGA) database to identify early diagnostic biomarkers for PAAD. Survival-related mRNAs were identified using a weighted gene co-expression network analysis (WGCNA), and then a linear prognostic model of seven long non-coding RNAs (lncRNAs) was established using univariate and multivariate Cox proportional hazards regression analyses, which is verified using a time-dependent receiver operating characteristic (ROC) curve analysis. Finally, according to the survival analysis, we constructed a survival-related competing endogenous RNA (ceRNA) network. Our results showed that: (1) The upregulated genes related to cell cycle-related pathway (including homologous recombination, DNA replication and mismatch repair) in PAAD can increase the proliferation ability of cancer cells; (2) The 7-lncRNA signature can predict the overall survival (OS) of PAAD patients; and (3) The key mRNAs and lncRNAs are involved in mutual regulation in the ceRNA network.
Highlights
Pancreatic adenocarcinoma (PAAD) is a serious pancreatic disease, pancreatic ductal adenocarcinoma (PDAC) accounts for >90% of all pancreatic cancer (Kleeff et al, 2016)
We performed survival analysis on the genes in the green module, and we found that four genes: maternal embryonic leucine zipper kinase (MELK), Aurora kinase A (AURKA), kinesin family 23 (KIF23) and checkpoint kinase 1 (CHEK1) were significantly related to overall survival (OS) (P < 0.05)
Great efforts have been made to elucidate the molecular mechanism underlying the pathogenesis of PAAD at the level of coding and non-coding genes, and to find molecular targets related to PAAD
Summary
Pancreatic adenocarcinoma (PAAD) is a serious pancreatic disease, pancreatic ductal adenocarcinoma (PDAC) accounts for >90% of all pancreatic cancer (Kleeff et al, 2016). There is no reliable method for screening for and early detection of PAAD, so most patients are diagnosed at an advanced stage of the disease ceRNA Network of PAAD (Tesfaye et al, 2018). PAAD has very few common genetic mutations and no clearly clinically relevant biomarkers. In this respect, the study on PAAD lags far behind other solid tumors (Gallego et al, 2017; Gallmeier and Gress, 2018). To reduce mortality and improve the detection and risk classification of PAAD, early diagnostic biomarkers (Le et al, 2016) and therapeutic targets urgently need to be determined
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