Abstract
Evidence indicates that aberrantly expressed long non-coding RNAs (lncRNAs) are involved in the development and progression of advanced gastric cancer (AGC). Using RNA sequencing data and clinical information obtained from The Cancer Gene Atlas, we combined differential lncRNA expression profiling and weighted gene co-expression network analysis to identify key lncRNAs associated with AGC progression and prognosis. Cancer susceptibility 19 (CASC19) was the top hub lncRNA among the lncRNAs included in the gene module most significantly correlated with AGC’s pathological variables. CASC19 was upregulated in AGC clinical samples and was significantly associated with higher pathologic TNM stage, pathologic T stage, lymph node metastasis, and poor overall survival. Multivariable Cox analysis confirmed that CASC19 overexpression is an independent prognostic factor for overall survival. Furthermore, quantitative real-time PCR assay confirmed that CASC19 expression in four human gastric cancer cells (AGS, BGC-823, MGC-803, and HGC-27) was significantly upregulated compared with human normal gastric mucosal epithelial cell line (GES-1). Functionally, CASC19 knockdown inhibited GC cell proliferation and migration in vitro. These findings suggest that CASC19 may be a novel prognostic biomarker and a potential therapeutic target for AGC.
Highlights
Gastric cancer (GC) is one of the most common malignant tumors of the digestive tract worldwide, and its morbidity and mortality are ranked 4th and 2nd, respectively, among all malignant tumors [1, 2]
Using RNA sequencing data and clinical information obtained from The Cancer Gene Atlas, we combined differential long non-coding RNAs (lncRNAs) expression profiling and weighted gene coexpression network analysis to identify key lncRNAs associated with advanced gastric cancer (AGC) progression and prognosis
Our results demonstrate the relevance of the hub lncRNA Cancer susceptibility 19 (CASC19) as predictor of tumor stage and overall survival, and suggest CASC19 is a novel biomarker of AGC and a potential therapeutic target
Summary
Gastric cancer (GC) is one of the most common malignant tumors of the digestive tract worldwide, and its morbidity and mortality are ranked 4th and 2nd, respectively, among all malignant tumors [1, 2]. Two-thirds of patients present with advanced GC (AGC) at initial diagnosis, and their 5-. Screening novel biomarkers to identify reliable therapeutic targets has become an urgent issue for the prevention and treatment of GC. LncRNAs are abundantly www.aging-us.com present in the human transcriptome and may exert oncogenic or tumor suppressor effects [5,6,7] by affecting expression of target genes at the epigenetic, transcriptional, and post-transcriptional levels, and by participating in such processes as chromatin modification, genomic imprinting, and intranuclear transport [8,9,10]. Several studies have reported an association between aberrantly expressed lncRNAs and the development and progression of AGC [11,12,13,14].
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