48 / 60
Page 48
conferenceseries
.com
Volume 09
Journal of Gastrointestinal & Digestive System
ISSN: 2161-069X
Gastro Congress 2019
July 08-09, 2019
July 08-09, 2019 | Zurich, Switzerland
14
th
Euro-Global Gastroenterology Conference
Toward understanding the molecular basis of esophageal squamous cell carcinoma
Ming Rong Wang
Cancer Institute and Hospital-CAMS & PUMC, China
E
sophageal squamous cell carcinoma (ESCC) is among the most common human cancers, with an overall five-
year survival rate of around 20%. To improve the diagnosis and prognosis of ESCC, we performed systematic
studies on the molecular alterations in the disease. Frequent gains of chromosomal bands 3q26, 8q24, 11q13,
losses of 3p14 and 9p21, amplifications of genes CCND1, EMS1 (CTTN), EGFR, PLK1, SKP2, PRKCI (PKCiota),
deletions of CDKN2A/B, FHIT and rearrangements of NTRK3, DTL and PTPRD were found. The mutation
profiling was characterized and potential therapeutic targets were identified. We further investigated intratumor
heterogeneity (ITH) of the molecular alterations and constructed phylogenetic trees for genomic evolution, in which
the mutations of ERBB4, FGFR2, BRCA2, ATM, TP53 and copy number changes of 11q13 and 9p21 were early
events and those of PI3K/MTOR pathway, KIT, AURKA, CCND2 and 3q26 were late. By proteomic techniques and
immunohistochemistry, multiple proteins were observed with high expression in tumor tissues but negative/low
expression in morphologically normal operative margins. Especially, copy number alterations of ANO1, CDKN2A,
and high expression of p63 and ANO1 were also present in precancerous lesions (dysplasia). We further explored
the mechanisms underlying the development and progression of ESCC and revealed that CRT, CTTN, PKCiota,
SKP2 and PLK1 enhanced cell motility and resistance to apoptosis and promoted tumor growth and metastasis via
activating the PI3K-AKT pathway, inhibiting beta-catenin degradation and up-regulating the apoptosis suppressor
Survivin. These findings extend our understanding of ESCC, providing theoretical foundation for elucidating
the mechanisms underlying the tumorigenesis of the esophagus and progression of ESCC and for developing
classification biomarkers and therapy targets for ESCC treatment.
wangmr2015@126.comJ Gastrointest Dig Syst 2019, Volume 09