Document Type
Article
Publication Date
5-1-2024
Original Citation
Suh Y,
Lee J,
George J,
Seol D,
Jeong K,
Oh S,
Bang C,
Jun Y,
Kong S,
Lee H,
Kim J,
Kim W,
Yang H,
Lee C.
RNA expression of 6 genes from metastatic mucosal gastric cancer serves as the global prognostic marker for gastric cancer with functional validation. British journal of cancer. 2024; 130(9):1571
Keywords
JGM, Stomach Neoplasms, Humans, Prognosis, Animals, Mice, Biomarkers, Tumor, Gastric Mucosa, Lymphatic Metastasis, Female, Male, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Machine Learning, Middle Aged
ISSN
1532-1827
PMID
38467827
DOI
https://doi.org/10.1038/s41416-024-02642-6
Grant
This work was supported by the Korean Healthcare Technology R&D project through the Korean Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI13C2148) and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF- 2020R1C1C1009225)
Abstract
BACKGROUND: Molecular analysis of advanced tumors can increase tumor heterogeneity and selection bias. We developed a robust prognostic signature for gastric cancer by comparing RNA expression between very rare early gastric cancers invading only mucosal layer (mEGCs) with lymph node metastasis (Npos) and those without metastasis (Nneg).
METHODS: Out of 1003 mEGCs, all Npos were matched to Nneg using propensity scores. Machine learning approach comparing Npos and Nneg was used to develop prognostic signature. The function and robustness of prognostic signature was validated using cell lines and external datasets.
RESULTS: Extensive machine learning with cross-validation identified the prognostic classifier consisting of four overexpressed genes (HDAC5, NPM1, DTX3, and PPP3R1) and two downregulated genes (MED12 and TP53), and enabled us to develop the risk score predicting poor prognosis. Cell lines engineered to high-risk score showed increased invasion, migration, and resistance to 5-FU and Oxaliplatin but maintained sensitivity to an HDAC inhibitor. Mouse models after tail vein injection of cell lines with high-risk score revealed increased metastasis. In three external cohorts, our risk score was identified as the independent prognostic factor for overall and recurrence-free survival.
CONCLUSION: The risk score from the 6-gene classifier can successfully predict the prognosis of gastric cancer.
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This work is licensed under a Creative Commons Attribution 4.0 International License.