Abstract 156P
Background
IDO1 (Indoleamine 2,3-dioxygenase 1) inhibits host anti-tumor immune response by exhausting tryptophan in tumor microenvironment, but the pathogenic mechanisms of IDO1 in gastric cancer (GC) cells need to be further explored.
Methods
The aim of this study was to use CCLE (Cancer Cell Line Encyclopedia) transcriptomic data of GC cell lines for WGCNA (Weighted Gene Co-expression Network Analysis) analysis, and explored the potential functions and mechanisms of IDO1 in GC progression in vitro and in vivo.
Results
The higher expression level of IDO1 was identified in 4 out of 7 GC cell lines. Increased IDO1 expression strongly promoted cell migration via its metabolite kynurenine and was associated with pathways of immune activation according to GSEA (Gene Set Enrichment Analysis). The functions of IDO1 were closely associated with extracellular matrix, collagen metabolic and catabolic process by WGCNA analysis. Among five hub genes (AXL, SGCE, COL12A1, ANTXR1, LOXL2), COL12A1 and LOXL2 were upregulated in GC tissues. IDO1 disclosed positive correlation with six collagen genes by coefficient matrix diagram. Knockdown of IDO1 decreased the expression of LOXL2, COL6A1, COL6A2 and COL12A1 in GC cells in both mRNA and protein levels. Of them, knockdown of COL12A1 inhibited cell migration more apparently than knockdown of others. IDO1 and COL12A1 revealed synergistic efficacy on promoting cell migration via a positive feedback sustained by MAPK pathway. This bioprocess was mediated by IDO1 metabolite kynurenine and integrin β1. A popliteal lymph node metastasis model was established for verifying metastatic promotion of IDO1 and COL12A1 in GC.
Conclusions
IDO1 and COL12A1 synergistically promoted GC metastasis. The novel findings suggested that both IDO1 and COL12A1 may be promising targets on anti-cancer treatment in GC.
Clinical trial identification
Editorial acknowledgement
Thank professor Yu for revising the abstract.
Legal entity responsible for the study
Yingyan Yu.
Funding
Has not received any funding.
Disclosure
The author has declared no conflicts of interest.
Resources from the same session
165P - Lenvatinib treatment for advanced hepatocellular carcinoma: The relationship between efficacy and safety
Presenter: Takayoshi Oikawa
Session: Poster display session
Resources:
Abstract
166P - The comparison between UGT1A1 single heterozygous and wild type regarding the clinical outcomes of fixed dose irinotecan monotherapy for advanced gastric cancer: Multicenter retrospective study
Presenter: Takahide Sasaki
Session: Poster display session
Resources:
Abstract
167P - Prognostic impact of the C-reactive protein/albumin ratio in advanced pancreatic cancer treated with GEM plus nab-PTX or FOLFIRINOX: Based on the results of a multicenter retrospective study (the NAPOLEON study)
Presenter: Akitaka Makiyama
Session: Poster display session
Resources:
Abstract
168P - A retrospective multicenter study evaluating the efficacy and safety of irinotecan in patients with advanced gastric cancer: Analysis of Glasgow Prognostic Score (GPS)
Presenter: Takuya Honda
Session: Poster display session
Resources:
Abstract
169P - M-phase phosphoprotein 8 promotes gastric cancer growth and metastasis via p53/Bcl-2 and EMT-related signalling pathways
Presenter: Yizhuo Wang
Session: Poster display session
Resources:
Abstract
170P - Surgery alone versus surgery combined with Chemotherapy: Survival patterns among patients with fibrolamellar hepatocellular carcinoma
Presenter: Yasmine Ashraf
Session: Poster display session
Resources:
Abstract
171P - The clinical value of prognostic nutritional index in patients with anastomotic leakage after minimally invasive esophagectomy
Presenter: Yan Wang
Session: Poster display session
Resources:
Abstract
172P - Preoperative neutrophil‐to‐lymphocyte ratio (NLR) predicts recurrence after surgery in patient with pancreatic neuroendocrine neoplasm (PanNEN)
Presenter: Takayuki Miura
Session: Poster display session
Resources:
Abstract
173P - Cancer stem-like phenotypes including immune surveillance and its responsible genes in induced liver cancer stem-like cells
Presenter: Ryouichi Tsunedomi
Session: Poster display session
Resources:
Abstract
174P - Progression of computer aided diagnosis on gastric cancer
Presenter: Yingyan Yu
Session: Poster display session
Resources:
Abstract