Tumorigenesis is a complex dynamic biological process that includes multiple steps of genetic and epigenetic alterations, aberrant expression of noncoding RNA, and changes in the expression profiles of coding genes. We call the collection of those perturbations in genome space the “cancer initiatome.” Long noncoding RNAs (lncRNAs) are pervasively transcribed in the genome and they have key regulatory functions in chromatin remodeling and gene expression. Spatiotemporal variation in the expression of lncRNAs has been observed in development and disease states, including cancer. A few dysregulated lncRNAs have been studied in cancers, but the role of lncRNAs in the cancer initiatome remains largely unknown, especially in esophageal squamous cell carcinoma (ESCC). We conducted a genome-wide screen of the expression of lncRNAs and coding RNAs from ESCC and matched adjacent nonneoplastic normal tissues. We identified differentially expressed lncRNAs and coding RNAs in ESCC relative to their matched normal tissue counterparts and validated the result using polymerase chain reaction analysis. Furthermore, we identified differentially expressed lncRNAs that are co-located and co-expressed with differentially expressed coding RNAs in ESCC and the results point to a potential interaction between lncRNAs and neighboring coding genes that affect ether lipid metabolism, and the interaction may contribute to the development of ESCC. These data provide compelling evidence for a potential novel genomic biomarker of esophageal squamous cell cancer. 1. Introduction Esophageal squamous cell carcinoma (ESCC) is one of the most common types of cancer, and it ranks among the main causes of cancer deaths worldwide [1]. There are marked regional variation and exceptionally high incidence in certain areas of China. Despite advances in multidisciplinary treatment of ESCC, 5-year survival rate remains poor. The initiatome [2] of ESCC is a complex dynamic biological process in genome space, and it may include multiple steps of genetic and epigenetic alterations [3], aberrations in expression of noncoding RNA (e.g., microRNAs) [4], and changes in the expression profile of coding genes [5, 6]. In past decades, expression profiling of coding genes has defined important signaling pathways involved in tumorigenesis. The latest knowledge of actively transcribed long noncoding RNAs (lncRNAs) from high-throughput sequencing is revealing an even greater complexity about cancer genome regulatory networks. LncRNAs are endogenous cellular RNA transcripts, ranging from 200 to 100,000
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