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
540P - Phase III study of serplulimab plus chemotherapy as first-line therapy for advanced squamous non-small cell lung cancer: ASTRUM-004 Asian subgroup
Presenter: Caicun Zhou
Session: Poster Display
Resources:
Abstract
541P - Integrated analysis of randomized controlled trials IMpower130 and IMpower132 for advanced non-squamous non-small cell lung cancer (NSCLC)
Presenter: Hibiki Udagawa
Session: Poster Display
Resources:
Abstract
542P - First-line HLX07 plus serplulimab with or without chemotherapy versus serplulimab plus chemotherapy in advanced/recurrent squamous non-small cell lung cancer: A phase II study
Presenter: Zhen Wang
Session: Poster Display
Resources:
Abstract
543P - A multicenter retrospective study to investigate risk factors for immune checkpoint inhibitor-induced pneumonitis in non-small cell lung cancer patients with comorbid interstitial pneumonia
Presenter: Yuriko Ishida
Session: Poster Display
Resources:
Abstract
544P - Single cell level investigation of blood cells representing immune checkpoint inhibitor response in lung adenocarcinoma patients
Presenter: Juyong Seong
Session: Poster Display
Resources:
Abstract
545P - Completion of pembrolizumab in advanced non-small cell lung cancer: Real-world outcomes after two years of therapy (COPILOT)
Presenter: Andrew Fantoni
Session: Poster Display
Resources:
Abstract
546P - Combination therapy with anti-PD-1 antibody plus angiokinase inhibitor exerts synergistic antitumor effect against malignant mesothelioma via tumor microenvironment modulation
Presenter: Akio Tada
Session: Poster Display
Resources:
Abstract
547P - Immunotherapy outcome in advanced/metastatic lung cancer patients in real-world experience: Indian data
Presenter: Naveen K
Session: Poster Display
Resources:
Abstract
548P - B-Myb acts as a mentor instant promoter in non-small cell lung cancer by modifying the PD-1/PD-L1 axis
Presenter: Pan Xu
Session: Poster Display
Resources:
Abstract
549P - Drug-induced interstitial lung disease in patients with non-small cell lung cancer treated with immunotherapy for postoperative recurrence: Evaluation of CT findings and histopathological findings of the background lung
Presenter: shodai fujimoto
Session: Poster Display
Resources:
Abstract