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
529P - Ramucirumab plus docetaxel after combination chemoimmunotherapy in patients with non-small cell lung cancer: A prospective observational study
Presenter: Tadaaki Yamada
Session: Poster Display
Resources:
Abstract
530P - MYC recruits tumor-associated macrophage to sustain metastatic malignancy of lung adenocarcinoma micropapillary subtype through epigenetic reprogramming
Presenter: Xuming Song
Session: Poster Display
Resources:
Abstract
531P - Effect of combinational targeted therapy for AXL and ATR against malignant mesothelioma cells
Presenter: Soichi Hirai
Session: Poster Display
Resources:
Abstract
532P - The changes of the serum SMRP levels is useful to predict the antitumor efficacy of ipilimumab plus nivolumab combination therapy in patients with malignant pleural mesothelioma
Presenter: Taiichiro Otsuki
Session: Poster Display
Resources:
Abstract
533P - Efficacy in the elderly NSCLC patients in SCORPION study: Phase II study of DTX plus RAM following platinum-based chemotherapy plus ICIs
Presenter: Teppei Yamaguchi
Session: Poster Display
Resources:
Abstract
534P - DSC2 promotes the proliferation, metastasis and drug resistance of lung cancer by activating the PI3K/AKT pathway
Presenter: Qi Li
Session: Poster Display
Resources:
Abstract
535P - Alteration in NKX2-1 CN reshapes the oncogenic, immunologic, and prognostic landscapes in NSCLC
Presenter: Herdee Gloriane Luna
Session: Poster Display
Resources:
Abstract
536P - The evaluation and long-term outcome of pulmonary metastasectomy for osteosarcoma: A 20-year experience of Shanghai Rujin Hospital
Presenter: Zhusheng Zhang
Session: Poster Display
Resources:
Abstract
537P - The impact of treatment-free interval on patient outcome after pulmonary metastasectomy for sarcoma
Presenter: Po-Kuei Hsu
Session: Poster Display
Resources:
Abstract
538P - First-line chemoimmunotherapy for metastatic thymic carcinoma
Presenter: Victoria Andreas
Session: Poster Display
Resources:
Abstract