Abstract 123P
Background
Incidence of sporadic early-onset colon cancer (EOCC) has increased worldwide. The molecular mechanisms in the tumor and the tumor microenvironment (TME) of EOCC as well as their clinical implications are not understood. The aim was to unravel unique spatial transcriptomic profiles in tumor epithelial cells and cancer-associated fibroblasts (CAFs) of EOCC compared to late-onset colon cancer (LOCC).
Methods
Initially, 26 sporadic colon cancer (CC) tissue samples from 26 patients were assessed. CC patients received surgery at SJHC and did not have previous therapies, MSI-H, hereditary CC family history, or inflammatory bowel disease. Patients were grouped into EOCC (<50 yrs) and LOCC (≥50 yrs) and analyzed using NanoString GeoMx DSP (NGDSP) and HTG EdgeSeq PIP platforms. Validation cohorts of EOCC and LOCC with transcriptomic data and clinical annotations were assessed from CC TCGA database and GEO datasets. Bioinformatic analysis included CIBERSORTx and NicheNET.
Results
CAFs having fibroblast associated protein positive expression (FAP(+) were significantly enriched in EOCC compared to LOCC tumors. EOCC patients with higher FAP mRNA levels in CAFs had shorter Overall Survival (OS, p < 0.029) and Disease-Free Survival (DFS, p < 0.038). Spatial transcriptomic analysis using NGDSP demonstrated that FAP(+) CAFs at the EOCC tumor invasive margin (TIM) had significant upregulation of WNT signaling and higher levels of fibroblast growth factor 20 (FGF20). Tumor epithelial cells at TIM of EOCC tumors, neighboring FAP(+) CAFs, showed significantly higher levels of fibroblast growth factor receptor 2 (FGFR2, p < 0.05) and PI3K/Akt signaling activation (p < 0.05). In-vitro assays showed FGF20 activates FGFR2-PI3K/Akt signaling in EOCC tumor cells.
Conclusions
High levels FAP(+) CAF in EOCC tumors represent a prognostic factor for DFS and OS. Comparing TIM, EOCC tumors had enhanced FAP(+) CAF cells with significant WNT signaling upregulation and increased FGF20 levels compared to LOCC. Conversely, tumor cells, neighboring FAP(+) CAFs, showed significant activation of FGFR2-PI3K/Akt signaling at the EOCC TIM.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
California Oncology Research Institute and the Stand-up to Cancer.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
551P - Real-world incidence and outcomes of immune-related adverse events in NSCLC patients
Presenter: Andrea Knox
Session: Poster Display
Resources:
Abstract
552P - TROPION-Lung05: Datopotamab deruxtecan (Dato-DXd) in Asian patients (pts) with previously treated non-small cell lung cancer (NSCLC) with actionable genomic alterations (AGAs)
Presenter: Yasushi Goto
Session: Poster Display
Resources:
Abstract
553P - Preceding plasma EGFR vs upfront tissue NGS for advanced NSCLC in the Chinese population: A single centre experience in Hong Kong
Presenter: Janet Du
Session: Poster Display
Resources:
Abstract
554P - Comparison of the analytical performance of endobronchial ultrasound-guided transbronchial needle aspiration and other sampling methods for the Oncomine Dx target test: An observational study
Presenter: Kazuhito Miyazaki
Session: Poster Display
Resources:
Abstract
555P - Quality of life in patients with stage IV non-small cell lung cancer and the influence of druggable mutations over time: A prospective, territory-wide study in Hong Kong
Presenter: Jason C S Ho
Session: Poster Display
Resources:
Abstract
556P - Results from the phase I study on efficacy and safety of iruplinalkib (WX-0593) for anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) patients who received prior second-generation ALK tyrosine kinase inhibitors (TKIs)
Presenter: xuezhi Hao
Session: Poster Display
Resources:
Abstract
557P - Longitudinal plasma proteomic profiling of EML4-ALK positive lung cancer receiving ALK-TKIs therapy
Presenter: Shasha Wang
Session: Poster Display
Resources:
Abstract
558P - Treatment duration and adherence of brigatinib as second-line treatment after crizotinib for ALK+ NSCLC in South Korea
Presenter: Jeong Eun Lee
Session: Poster Display
Resources:
Abstract
559P - Comprehensive survey of AACR GENIE database revealed a wide range of TMB distribution among all three classes (I, II, III) of BRAF mutated NSCLC
Presenter: Zhaohui Arter
Session: Poster Display
Resources:
Abstract
560P - Triple-targeted therapy of dabrafenib, trametinib and osimertinib for the treatment of acquired BRAF V600E mutation after progression on EGFR-TKIs in advanced EGFR-mutant NSCLC
Presenter: Chengdi Weng
Session: Poster Display
Resources:
Abstract