Abstract
Primary SCEC is a rare malignancy without established treatment strategy. Although previous studies suggested that there were similarities between SCEC and SCLC in clinical manifestation and pathological morphology, genetic studies on this highly malignant tumor remained sparse. This study was designed to investigate the gene expression profile of SCEC, and compare it with the known expression data of SCLC and EC. De novo expression array analysis was performed on three pairs of frozen tissues of primary SCEC and corresponding normal samples from institutional tissue bank using the Affymetrix HG U133 plus 2.0 array. These data were complemented with public domain expression data sets from the GEO repository using the same working platforms during the last 3 years, which included primary SCLC, primary EC [esophageal squamous carcinoma (ESCC), adenocarcinoma (EAC)], and normal lung/esophagus specimens (series GSE30219, GSE26886). After individual normalization, primary tumors were submitted to statistical analysis (GeneSpring GX 12.5) for identifying differentially expressed genes (DEGs) as compared with their paired normal tissues. Gene enrichments with functions and genes interactions were analyzed by DAVID 6.7 and STRING 9.0, respectively. SCEC had more DEGs in common with SCLC than EC (829 vs 450; false discovery rate <0.01, fold change ≥2), leading to a greater correlation between SCEC and SCLC (Pearson correlation coefficient was 0.60 for SCEC vs SCLC, 0.51 or 0.45 for SCEC vs ESCC or EAC, the coefficient was 0.73 for ESCC vs EAC). Similar findings were obtained by Principal Component Analysis (PCA) using all DEGs retrieved from these four groups. Functional annotation showed that a higher proportion of pathways and biological processes were in common between SCEC and SCLC, which were associated with cell cycle (mitosis), DNA replication, telomere maintenance, DNA repair, P53 and RB pathway (Benjamini p <0.05). Comparing with EC, SCEC shared more co-up regulated DEGs coding for the aforementioned common pathways with SCLC (584 vs 155). In addition, SCEC and SCLC possessed overlapped gene interactive network with CENPF, NEK2, KIF11, TMPO, FOXM1 as common skeleton centered by NUF2. This study is the first attempt to examine the genomic signatures of SCEC at the transcription level, and compare the expression profiles between SCEC, SCLC and EC. Our preliminary data indicate that SCEC and SCLC display notably similar patterns of gene expression on mitosis and DNA repair, suggesting that the two diseases were regulated by kindred transcriptional networks. Further validation study is warranted.
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