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Poster Display session 2

5644 - Development and validation of a metastasis-associated immune prognostic model for concurrent metastatic colorectal cancer

Date

29 Sep 2019

Session

Poster Display session 2

Topics

Tumour Site

Colon and Rectal Cancer

Presenters

Zhiwen Luo

Citation

Annals of Oncology (2019) 30 (suppl_5): v198-v252. 10.1093/annonc/mdz246

Authors

Z. Luo, H. Zhao, Z. Li, R. Mao, J. Zhao, D. Ge, F. Zhang, Y. Zhou, X. Chen, J. Cai, X. Bi

Author affiliations

  • Department Of Hepatobiliary Surgery, National Cancer Center/national Clinical Research Center For Cancer/cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021 - Beijing/CN

Resources

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Abstract 5644

Background

The recurrence of concurrent metastatic colorectal cancer (mCRC) after primary surgery and subsequent irinotecan-based therapies is still a challenge. Fong’s CRS criteria prompted us to identify mCRC with high recurrence risk, and whether there are any specific gene signatures identifing those mCRC? Therefore, we aimed to identify gene signatures and investigated how they regulate the mCRC immunophenotype and thus affect the prognosis..

Methods

We investigated RNA expression in different populations and platforms. Based on metastasis-related genes, a metastatic evaluation model (MEM) was developed, which divided mCRCs into high and low recurrence risk groups. Further investigation of these two groups made an immune prognostic model (IPM) based on differentially expressed immune-related genes. Then, the influence of the IPM on mCRC’s immune microenvironment was comprehensively analyzed by bioinformatics.

Results

High recurrence risk in mCRC after surgery and subsequent irinotecan-based therapies was attributed to the down-regulation of immune response, which was influenced mainly by 3 metastasis-related genes (BAMBI, F13A1, LCN2) and 3 immune-related genes (SLIT2, CDKN2A, CLU). MEM and IPM were established and validated based on 231 mCRC patients to differentiate patients with a low or high risk of recurrence. A nomogram was established. Functional enrichment analysis showed immune response and immune system diseases pathway represented the major function and pathway, respectively, related to IPM genes. Moreover, we found IPM high-risk group had higher fractions of Tregs and CD8+ T cells, lower fractions of neutrophils and eosinophils, and presented higher expression of CCR8 than low-risk group.

Conclusions

The recurrence of mCRC after primary surgery and subsequent irinotecan-based therapies is strongly related to the immune microenvironment. Our IPM may have important implications for identifying subgroups of mCRC with low or high risk of recurrence, and give new insights in personal chemotherapy and immunotherapy for mCRC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

CICAMS.

Funding

Initial Project 2018-1-4021 Beijing Municipal Health Commission.

Disclosure

All authors have declared no conflicts of interest.

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