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
175P - Hypermethylation of the PCDHB15 promoter predicts the prognosis in gastric cancer
Presenter: Yu-ting Lee
Session: Poster display session
Resources:
Abstract
176P - DCLK1 promotes tumour invasion and metastasis through epithelial-mesenchymal transition and the MEK/ERK pathway in esophageal squamous cell carcinoma
Presenter: Jiannan Yao
Session: Poster display session
Resources:
Abstract
177P - Comparison of nab-paclitaxel plus ramcirumab and paclitaxel plus ramcirumab in patients with pretreated metastatic gastric cancer
Presenter: Yosuke Horita
Session: Poster display session
Resources:
Abstract
178P - Chief cell in stomach have stem cell activity and potential to develop gastric cancer
Presenter: Akihiro Yamamura
Session: Poster display session
Resources:
Abstract
179P - Postoperative Adjuvant transarterial chemoembolization versus surgery alone for resected hepatocellular carcinoma: A propensity-score matching study
Presenter: Mingyu Chen
Session: Poster display session
Resources:
Abstract
180P - LHPP inhibit the cell proliferation and EMT via the TGFβ/SMAD3 signaling pathway in iCCA
Presenter: Dan Wang
Session: Poster display session
Resources:
Abstract
181P - The emerging role of third-line gemcitabine plus nab-paclitaxel in advanced pancreatic adenocarcinoma
Presenter: Andrew Dean
Session: Poster display session
Resources:
Abstract
182P - Durable response to second-line m-FOLFIRINOX for advanced pancreatic adenocarcinoma in patients with performance status of two or less
Presenter: Adarsh Das
Session: Poster display session
Resources:
Abstract
183P - Epidemiologic profile of gastric cancer in East Azerbaijan, Iran: 2 years population-based cancer registry results
Presenter: Pooneh Jabbaripour
Session: Poster display session
Resources:
Abstract
184P - Expression pattern of CDK12 protein in gastric cancer and its positive correlation with CD8+ cell density and CCL12 expression
Presenter: Jun Ji
Session: Poster display session
Resources:
Abstract