Molecular subtyping of esophageal squamous cell carcinoma by large-scale transcriptional profiling: Characterization, therapeutic targets, and prognostic value

Abstract

The tumor heterogeneity of the transcriptional profiles is independent of genetic variation. Several studies have successfully identified esophageal squamous cell carcinoma (ESCC) subtypes based on the somatic mutation profile and copy number variations on the genome. However, transcriptome-based classification is limited. In this study, we classified 141 patients with ESCC into three subtypes (Subtype 1, Subtype 2, and Subtype 3) via tumor sample gene expression profiling. Differential gene expression (DGE) analysis of paired tumor and normal samples for each subtype revealed significant difference among subtypes. Moreover, the degree of change in the expression levels of most genes gradually increased from Subtype 1 to Subtype 3. Gene set enrichment analysis (GSEA) identified the representative pathways in each subtype: Subtype 1, abnormal Wnt signaling pathway activation; Subtype 2, inhibition of glycogen metabolism; and Subtype 3, downregulation of neutrophil degranulation process. Weighted gene co-expression network analysis (WGCNA) was used to elucidate the finer regulation of biological pathways and discover hub genes. Subsequently, nine hub genes (CORO1A, CD180, SASH3, CD52, CD300A, CD14, DUSP1, KIF14, and MCM2) were validated to be associated with survival in ESCC based on the RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) database. The clustering analysis of ESCC granted better understanding of the molecular characteristics of ESCC and led to the discover of new potential therapeutic targets that may contribute to the clinical treatment of ESCC.

Investigation on the molecular mechanism of SPA interference with osteogenic differentiation of bone marrow mesenchymal stem cells

“…Functional enrichment analysis showed that Kif14 was mainly enriched in 'macroautophagy' and 'pyrimidine metabolism'. In addition, Kif14 was also active in signaling pathways such as Wnt signaling 54 , 55 , Hedgehog signaling 56 , 57 , and PI3K/Akt signaling 58 . To date, there have been no studies on the direct involvement of the above biomarkers in the osteogenic differentiation of MSCs.…”

Characteristics of auto-quantified tumor-infiltrating lymphocytes and the prognostic value in adenocarcinoma of the esophagogastric junction, gastric adenocarcinoma, and esophageal squamous cell carcinoma

“…Given the advanced or metastatic nature of many gastroesophageal cases at diagnosis, the overall 5-year survival rate remains less than 20% in developing countries [ 2 , 3 ]. The main factors affecting gastroesophageal cancers prognosis include tumor staging and grading, treatment method, living condition, and genetic marker [ 4 , 5 ]. However, as a transitional region tumor from esophageal squamous epithelium to the gastric adenoid epithelium, it is possible that the oncological principles for esophageal and gastric cancer are not directly applicable to junctional cancer [ 6 ].…”