Comprehensive analysis of differential co-expression patterns reveal transcriptional dysregulation mechanism and identify novel prognostic lncRNAs in esophageal squamous cell carcinoma

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide and occurs at a relatively high frequency in People’s Republic of China. However, the molecular mechanism underlying ESCC is still unclear. In this study, the mRNA and long non-coding RNA (lncRNA) expression profiles of ESCC were downloaded from the Gene Expression Omnibus database, and then differential co-expression analysis was used to reveal the altered co-expression relationship of gene pairs in ESCC tumors. A total of 3,709 mRNAs and 923 lncRNAs were differentially co-expressed between normal and tumor tissues, and we found that most of the gene pairs lost associations in the tumor tissues. The differential regulatory networking approach deciphered that transcriptional dysregulation was ubiquitous in ESCC, and most of the differentially regulated links were modulated by 37 TFs. Our study also found that two novel lncRNAs (ADAMTS9-AS1 and AP000696.2) might be essential in the development of ectoderm and epithelial cells, which could significantly stratify ESCC patients into high-risk and low-risk groups, and were much better than traditional clinical tumor markers. Further inspection of two risk groups showed that the changes in TF-target regulation in the high-risk patients were significantly higher than those in the low-risk patients. In addition, four signal transduction-related DCmRNAs (ERBB3, ENSA, KCNK7, MFSD5), which were differentially co-expressed with the two lncRNAs, might also have the predictive capacity. Our findings will enhance the understanding of ESCC transcriptional dysregulation from a view of cross-link of lncRNA and mRNA, and the two-lncRNA combination may serve as a novel prognostic biomarker for clinical applications of ESCC.

Systematic analysis of lncRNA–miRNA–mRNA competing endogenous RNA network identifies four-lncRNA signature as a prognostic biomarker for breast cancer

“…ADAMTS9-AS1 is an antisense lncRNA, and growing evidence has implicated that a large amount of antisense lncRNAs play crucial roles in the cancer [ 35 , 36 ]. Li et al [ 37 ] reported that ADAMTS9-AS1 could predict the survival status of patients with esophageal squamous cell carcinoma. Another study has also indicated a prognostic role of ADAMTS9-AS1 in patients with colon adenocarcinoma [ 38 ].…”

Identification of a TLR-Induced Four-lncRNA Signature as a Novel Prognostic Biomarker in Esophageal Carcinoma

“…Of four lncRNAs biomarkers, AP000696.1 is essential in the development of ectoderm and epithelial cells, and may sever as prognostic biomarker (Li et al, 2017). It has been reported that LINC00900 is significantly up-regulated by all-trans-retinoic acid and down-regulated by vitamin D (Riege et al, 2017).…”

Comprehensive analysis of the aberrantly expressed lncRNA‑associated ceRNA network in breast cancer

“…Wang et al (36) revealed that antisense lncRNA ADAMTS9-AS1 was associated with the nearby coding gene ADAMTS9, which was involved in ovarian cancer progression. Li et al (37) identified that the lncRNA ADAMTS9-AS1 served as a novel prognostic biomarker for clinical application in esophageal squamous cell carcinoma. Crippa et al (38) hypothesized that LINC00536 disruption may have contributed to the onset of the clinical trichorhinophalangeal syndrome-like phenotype.…”