Multi-omic characterization of early-onset esophagogastric cancer
Abstract Using a large real-world database with matched genomic and transcriptomic data, we characterized clinical and molecular differences between patients with early-onset esophagogastric cancer (EOEGC; <50 years), intermediate-onset esophagogastric cancer (IOEGC; 50-65 years), and average-ons...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-025-01030-4 |
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| author | Lawrence W. Wu Sachin Kumar Deshmukh Sharon Wu Joanne Xiu Sung Joo Jang Jimyung Park Vincent K. Lam Emil Lou Sanjay Goel Rachna T. Shroff Ryan H. Moy |
| author_facet | Lawrence W. Wu Sachin Kumar Deshmukh Sharon Wu Joanne Xiu Sung Joo Jang Jimyung Park Vincent K. Lam Emil Lou Sanjay Goel Rachna T. Shroff Ryan H. Moy |
| author_sort | Lawrence W. Wu |
| collection | DOAJ |
| description | Abstract Using a large real-world database with matched genomic and transcriptomic data, we characterized clinical and molecular differences between patients with early-onset esophagogastric cancer (EOEGC; <50 years), intermediate-onset esophagogastric cancer (IOEGC; 50-65 years), and average-onset esophagogastric cancer (AOEGC; >65 years). We analyzed clinicopathologic, whole transcriptome, and DNA-sequencing data from 5175 patient samples (EOEGC, n = 530; IOEGC, n = 1744; AOEGC, n = 2901) from the Caris Life Sciences database. Immune deconvolution was performed with quanTIseq and pathway enrichment with Gene Set Enrichment Analysis (GSEA). Real-world overall survival was estimated from insurance claims data. Prevalence of EOEGC was higher in patients who were Black, Asian, Hispanic/Latino, and female. Patients with EOEGC had higher proportion of CDH1 mutations; FGFR2, CCNE1, MYC copy number alterations; and ARHGAP26 fusions. Patients with EOEGC had decreased prevalence of immune-oncology markers of microsatellite instability-high, tumor mutation burden-high, and PD-L1 positivity. Immune microenvironment analysis identified significant enrichment of M2 macrophages and decreased M1 macrophages in patients with EOEGC. GSEA identified enrichment of epithelial mesenchymal transition and coagulation pathways in patients with EOEGC. This large real-world characterization of age-stratified esophagogastric cancer found that EOEGC was associated with significant racial, ethnic, and gender differences, and notable molecular differences that may have prognostic and therapeutic implications. |
| format | Article |
| id | doaj-art-bc47d3aa13db4b05bf81ebbde6bf5a69 |
| institution | Kabale University |
| issn | 2397-768X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-bc47d3aa13db4b05bf81ebbde6bf5a692025-08-20T03:45:40ZengNature Portfolionpj Precision Oncology2397-768X2025-07-019111010.1038/s41698-025-01030-4Multi-omic characterization of early-onset esophagogastric cancerLawrence W. Wu0Sachin Kumar Deshmukh1Sharon Wu2Joanne Xiu3Sung Joo Jang4Jimyung Park5Vincent K. Lam6Emil Lou7Sanjay Goel8Rachna T. Shroff9Ryan H. Moy10Division of Hematology/Oncology, Columbia University Irving Medical CenterCaris Life SciencesCaris Life SciencesCaris Life SciencesDivision of Surgical Sciences, Columbia University Irving Medical CenterDivision of Hematology/Oncology, Columbia University Irving Medical CenterJohns Hopkins Sidney Kimmel Comprehensive Cancer CenterDivision of Hematology, Oncology and Transplantation, University of MinnesotaRutgers Cancer Institute of New JerseyDivision of Hematology and Oncology, University of Arizona Cancer CenterDivision of Hematology/Oncology, Columbia University Irving Medical CenterAbstract Using a large real-world database with matched genomic and transcriptomic data, we characterized clinical and molecular differences between patients with early-onset esophagogastric cancer (EOEGC; <50 years), intermediate-onset esophagogastric cancer (IOEGC; 50-65 years), and average-onset esophagogastric cancer (AOEGC; >65 years). We analyzed clinicopathologic, whole transcriptome, and DNA-sequencing data from 5175 patient samples (EOEGC, n = 530; IOEGC, n = 1744; AOEGC, n = 2901) from the Caris Life Sciences database. Immune deconvolution was performed with quanTIseq and pathway enrichment with Gene Set Enrichment Analysis (GSEA). Real-world overall survival was estimated from insurance claims data. Prevalence of EOEGC was higher in patients who were Black, Asian, Hispanic/Latino, and female. Patients with EOEGC had higher proportion of CDH1 mutations; FGFR2, CCNE1, MYC copy number alterations; and ARHGAP26 fusions. Patients with EOEGC had decreased prevalence of immune-oncology markers of microsatellite instability-high, tumor mutation burden-high, and PD-L1 positivity. Immune microenvironment analysis identified significant enrichment of M2 macrophages and decreased M1 macrophages in patients with EOEGC. GSEA identified enrichment of epithelial mesenchymal transition and coagulation pathways in patients with EOEGC. This large real-world characterization of age-stratified esophagogastric cancer found that EOEGC was associated with significant racial, ethnic, and gender differences, and notable molecular differences that may have prognostic and therapeutic implications.https://doi.org/10.1038/s41698-025-01030-4 |
| spellingShingle | Lawrence W. Wu Sachin Kumar Deshmukh Sharon Wu Joanne Xiu Sung Joo Jang Jimyung Park Vincent K. Lam Emil Lou Sanjay Goel Rachna T. Shroff Ryan H. Moy Multi-omic characterization of early-onset esophagogastric cancer npj Precision Oncology |
| title | Multi-omic characterization of early-onset esophagogastric cancer |
| title_full | Multi-omic characterization of early-onset esophagogastric cancer |
| title_fullStr | Multi-omic characterization of early-onset esophagogastric cancer |
| title_full_unstemmed | Multi-omic characterization of early-onset esophagogastric cancer |
| title_short | Multi-omic characterization of early-onset esophagogastric cancer |
| title_sort | multi omic characterization of early onset esophagogastric cancer |
| url | https://doi.org/10.1038/s41698-025-01030-4 |
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