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
YO10 - Rectal Follicular Dendritic Cell Sarcoma
Presenter: Kripa Bajaj
Session: Poster display session
Resources:
Abstract
YO11 - Postoperative metastasis prediction based on portal vein circulating tumor cells detected by flow cytometry in periampullary or pancreatic cancer
Presenter: Lianyuan Tao
Session: Poster display session
Resources:
Abstract
YO12 - Case report of Hepatic EBV-associated smooth muscle tumor in AIDS patient
Presenter: Gorawich Kerkarchachai
Session: Poster display session
Resources:
Abstract
YO13 - IgG4-related pseudo-tumor of the kidney and multiple organ involvement mimicked malignancy
Presenter: Wasamol Mahaparn
Session: Poster display session
Resources:
Abstract
YO14 - Urachal Adenocarcinoma: Case Report
Presenter: Michelle Joane Alcantara
Session: Poster display session
Resources:
Abstract
YO15 - Concurrent Atezolizumab-Radiotherapy in Locally Recurrent Urinary Bladder Carcinoma: A Case Report
Presenter: Ma. Angelle Lalaine Dantes
Session: Poster display session
Resources:
Abstract
YO16 - Clear cell RCC with synchronous metastasis at transplanted kidney and bone in patient post Cadaveric donor kidney transplantation
Presenter: Punyaporn Cheewasathianchai
Session: Poster display session
Resources:
Abstract
YO17 - Serous ovarian cancer treated with palbociclib and letrozole
Presenter: Dai Wee Lee
Session: Poster display session
Resources:
Abstract
YO18 - A patient with Peutz-Jegher syndrome who incidentally found sex cord stromal tumor: a case report
Presenter: Pongput Pimsa
Session: Poster display session
Resources:
Abstract
YO19 - A case of CLL/SLL with transdifferentiation to dendritic cell tumor and possibly a hybrid lymphodendritic cell neoplasm:The missing link?
Presenter: Yanping Chen
Session: Poster display session
Resources:
Abstract