Specific markers for response to FOLFOX4-ATRA therapy
tumor, SD, PD, 3D-DIA, tumors
TUMOR, TUMORS
We performed an exploratory study to identify molecular markers that could predict the efficacy of FOLFOX4-ATRA treatment at the pre-treatment. We measured the protein expression in blood samples from patients with different response evaluations (PD, SD, PR, and CR) on the two treatment arms using the 3D-DIA proteomics assays. We compared the protein expression between any two response evaluations within each treatment arm and identified 80 proteins that were significantly differentially expressed across the different response evaluations (Then we further analyzed the interaction effects of treatment arm and response evaluation at the pre-treatment and identified 17 proteins that were uniquely differentially expressed in the FOLFOX4-ATRA arm compared to the FOLFOX4 alone arm (adjusted In addition, we also compared the differences in gene expression between the tumors of the responsive (CR, PR) and nonresponsive (PD) patients by transcriptome sequencing. There were 1017 genes significantly upregulated and 916 genes significantly downregulated in the response group vs. the nonresponse group. By analyzing the same signaling pathways of enriched genes from tumor tissues and proteins from plasma, we found that the significant genes and proteins regulated by FOLFOX4-ATRA were involved in ECM receptor interaction and complement and coagulation cascade signaling according to the Gene Ontology and KEGG pathway enrichment analysis. Furthermore, the differentially expressed genes from tumor tissues within these two signaling pathways can be grouped into three clusters according to the STRING database (Fig. 