Title:Proteomic and Metabolic Signatures of Esophageal Squamous Cell Carcinoma
Volume: 16
Issue: 8
Author(s): Kubra Karagoz, Heather L. Lehman, Douglas B. Stairs, Raghu Sinha, Kazim Y. Arga
Affiliation:
关键词:
系统生物学,生物医学,功能基因组学,食管鳞状细胞癌,生物标志物。
摘要: Esophageal squamous cell carcinoma (ESCC), which is the most
common subtype of esophageal cancers, is the sixth leading cause of cancer
deaths worldwide with a five-year survival rate of 19%. Identification of efficient
biomarkers for early detection and better understanding of the molecular
mechanisms of ESCC may offer reduced mortality. However, proper biomarkers
for clinical diagnosis and prognosis have not been defined yet. In the presented
study, we employed a systematic and integrative ‘omics’ strategy to reconstruct
networks of transcriptional regulation and protein-protein interaction to identify
novel biomarkers, potential molecular targets, and mechanisms of transcriptional
control in ESCC. Towards this end, we revealed 30 down-regulated and 21 upregulated
genes as ESCC specific biomarkers since these were differentially expressed between 91
ESCC tumor samples compared to normal tissues in five different datasets. We report the association
of ACPP, C2orf54, DYNLT3, ENDOU, FMO2, and KANK1 (down-regulated genes) and COL10A1,
FNDC3B, HOMER3, MARCKSL1, and RFC4 (up-regulated genes) to ESCC for the first time.
Further, the ESCC driven molecular pathways were also constructed to elucidate the molecular
mechanism of the disease; specifically several metabolic pathways were down-regulated while the
signaling pathways were up-regulated. Additionally, reporter metabolites for ESCC were analyzed
and metabolic dysfunction was ascertained in arachidonic acid metabolism and steroid hormone
biosynthesis pathways. The multi-omics network strategy presented here may enable discovery of
novel biomarkers and targets for personalized medicine in ESCC patients.