Abstract 411P
Background
Gastrointestinal stromal tumor (GIST) is a type of mesenchymal tumor and has KIT mutations in 80–90% of the cases. The development of tyrosine kinase inhibitors have greatly improved patient outcomes. We have previously described association between lower pfetin (KCTD12) expression and poor prognosis in the GIST patients (Ref 1. Suenara Y et al. Clin Cancer Res2008). In this study, to investigate the protein profiles of kit expression, we performed comprehensive protein expression analysis using the gastric tumor cell lines and surgical specimens in GIST.
Methods
We performed KITgene knockdown using siRNA inthe GIST cell line (T1 cell line) and generated the protein expression profiling data by i-TRAQ. Based on this i-TRAQ protein profiling data from the T1 cell line, we referenced our previously published protein expression analysis databases associated with GIST prognosis in the patient samples (Ref 1.) and compared the protein profile of KIT-associated proteins (T1 cell line) and prognosis-associated protein (patient samples).
Results
In our study, the i-TRAQ profiling method detected expression of approximately 1500–2000 proteins. In KITknockdown cells, 125 proteins were identified to have statistically different expression (p < 0.05). Based on our previously published GIST prognosis protein profile database (using 17 patient tissue samples), 25 proteins were identified to be statistically significant (p < 0.05). Upon comparing the prognosis database with theKIT knockdown database, 6 proteins were identified as common proteins.In particular, the heat shock protein (HSP) 90-beta, which has been previously shown to contribute to the growth of cancer cells, was identified as a critical protein in the biological behavior of GIST.
Conclusions
HSP 90-beta is currently considered as a therapeutic target for HSP 90 inhibitors against imatinib-resistant GIST. Our data suggests that the differentiation and cell growth of GIST may be enhanced by the identified proteins, which are in turn induced by KIT. We believe that our established protein profile data will help in improving the understanding of malignant behaviors in GIST.
Clinical trial identification
HSP 90-betaplay an important role in the tumor progression of GISTs.
Editorial acknowledgement
This study was supported by Grant-in-Aid from the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant Number #19K22694, #19H03789 and #15KK0353 to Y.S. ; #17K08730 to T.S.; #17K10987to K.K.; #19K16753 to K.A.; #18K15329 to T.O. , # 18K16634 to Y.K.) and Leading Advanced Projects for Medical Innovation (LEAP) (Grant Number # JP18am0001009) and the Practical Research for Innovative Cancer Control (Grant Number # JP18ck0106252) from the Japan Agency for Medical Research and Development.
Legal entity responsible for the study
Juntendo University.
Funding
This study was supported by Grant-in-Aid from the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant Number #19K22694, #19H03789 and #15KK0353 to Y.S. ; #17K08730 to T.S.; #17K10987to K.K.; #19K16753 to K.A.; #18K15329 to T.O. , # 18K16634 to Y.K.) and Leading Advanced Projects for Medical Innovation (LEAP) (Grant Number # JP18am0001009) and the Practical Research for Innovative Cancer Control (Grant Number # JP18ck0106252) from the Japan Agency for Medical Research and Development.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
97P - The role of adjuvant chemotherapy according to the status of surgical margin in rectal cancer
Presenter: Jong Hoon Lee
Session: Poster display session
Resources:
Abstract
98P - Influence of DPYD*9, DPYD*6 and GSTP1 ile105val genetic polymorphisms on capecitabine and oxaliplatin (CAPOX) associated toxicities in colorectal cancer patients
Presenter: Ashok Varma
Session: Poster display session
Resources:
Abstract
99P - Patient-derived tumour model by new culture method leading to the precision medicine
Presenter: Norikatsu Miyoshi
Session: Poster display session
Resources:
Abstract
100P - Clinical impact and carcinogenic mechanism of NCAPG overexpression in colon cancer
Presenter: Kai-Yuan Lin
Session: Poster display session
Resources:
Abstract
101P - Combined cellular immunotherapy and chemotherapy improves clinical outcome and displays safety in the treatment of patients with colorectal cancer
Presenter: Chang Wang
Session: Poster display session
Resources:
Abstract
102P - Clinical features of anorectal cancer in patients with Crohn’s disease: Japanese single center study
Presenter: Kazuhiro Watanabe
Session: Poster display session
Resources:
Abstract
103P - Contrast-enhanced CT-based textural parameters as potential prognostic factors of survival for colorectal cancer patients receiving targeted therapy
Presenter: Yanfei Yang
Session: Poster display session
Resources:
Abstract
104P - Prognostic significance of tumour location to the oncologic outcome of colon cancer
Presenter: Sare Hosseini
Session: Poster display session
Resources:
Abstract
105P - Detection and clinical significance of circulating tumour cells in patients with rectal cancer
Presenter: Shuohui Dong
Session: Poster display session
Resources:
Abstract
106P - The risk of malignization incidence in patients with polyps and polyposis of the colon and rectum
Presenter: Yakov Ten
Session: Poster display session
Resources:
Abstract