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
528P - High-biologically effective dose radiotherapy may improve local control of small cell lung cancer patients with brain metastases: A propensity-matching analysis
Presenter: Qingyang Zhuang
Session: Poster display session
Resources:
Abstract
530P - Prognostic value of C-reactive protein, albumin and C-reactive protein to albumin ratio in small cell lung cancer: A meta-analysis
Presenter: Carla Emille Barbon
Session: Poster display session
Resources:
Abstract
531TiP - CANOPY-A: A phase III, placebo-controlled study of canakinumab as adjuvant therapy in patients (pts) with surgically resected NSCLC
Presenter: Byoung Chul Cho
Session: Poster display session
Resources:
Abstract
532TiP - CANOPY-1: A phase III, placebo-controlled study of pembrolizumab (PEM) plus platinum-based doublet chemotherapy (Ctx) with/without canakinumab in untreated patients (pts) with stage IIIB/IIIC-IV NSCLC
Presenter: Daniel Shao Weng Tan
Session: Poster display session
Resources:
Abstract
533TiP - CANOPY-2: A phase III, placebo-controlled study of canakinumab with or without docetaxel in patients (pts) with NSCLC previously treated with PD-(L)1 inhibitors and platinum-based chemotherapy (Ctx)
Presenter: Darren Lim
Session: Poster display session
Resources:
Abstract
534TiP - A randomized phase III study of carboplatin plus nab-paclitaxel with or without nintedanib for NSCLC with IPF (J-SONIC)
Presenter: Kohei Otsubo
Session: Poster display session
Resources:
Abstract
535TiP - Phase II study of atezolizumab for pretreated advanced / recurrent non-small cell lung cancer with idiopathic interstitial pneumonia (TORG1936 / AMBITIOUS study)
Presenter: Satoshi Ikeda
Session: Poster display session
Resources:
Abstract
536TiP - INSIGHT 2: Tepotinib plus osimertinib in patients with EGFR-mutant NSCLC having acquired resistance to EGFR TKIs due to MET-amplification: A phase II trial in progress study
Presenter: James C-H Yang
Session: Poster display session
Resources:
Abstract
YO8 - Carcinosarcoma of the Breast in a Filipino Female: A Case Report
Presenter: Ma. Angelle Lalaine Dantes
Session: Poster display session
Resources:
Abstract
YO9 - Small Malignant Phyllodes Tumor of the Breast with Metastases to the Lung and Bone
Presenter: Gusti Harti
Session: Poster display session
Resources:
Abstract