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
310P - A study on the prediction of recurrence site of endometrial cancer using various machine learning techniques
Presenter: Wonkyo Shin
Session: Poster Display
Resources:
Abstract
311P - Circulating cytokines in the differential diagnosis of endometrial cancer
Presenter: Tatyana Abakumova
Session: Poster Display
Resources:
Abstract
312P - Molecular and genetic features of squamous cell carcinoma of vulvar cancer depending on HPV status
Presenter: Visola Navruzova
Session: Poster Display
Resources:
Abstract
313P - Efficacy and safety of oral metronomic chemotherapy in recurrent refractory advanced gynaecological cancer: Experience from regional cancer center of eastern India
Presenter: Ranti Ghosh
Session: Poster Display
Resources:
Abstract
314P - Perioperative outcomes in advanced epithelial ovarian cancer treated with neoadjuvant bevacizumab and chemotherapy: Real-world experience from an Indian cancer centre
Presenter: Upasana Palo
Session: Poster Display
Resources:
Abstract
315P - Real-world experience of niraparib as maintenance therapy in newly diagnosed advanced ovarian cancer: A single-center retrospective study
Presenter: Wenxin Liu
Session: Poster Display
Resources:
Abstract
316P - First evidence of olaparib maintenance therapy in patients with newly diagnosed BRCA wild-type ovarian cancer: A real-world multicenter study
Presenter: Jing Li
Session: Poster Display
Resources:
Abstract
317P - Attitudes of Israeli gynecologists towards risk reduction salpingo-oophorectomy at hysterectomy for benign conditions and the use of hormonal therapy
Presenter: wisam Assaf
Session: Poster Display
Resources:
Abstract
319P - Survival prediction for ovarian cancer patients from Taiwan cancer registry data
Presenter: Tzu-Pin Lu
Session: Poster Display
Resources:
Abstract
320P - Treatment patterns and outcomes in Indian patients with advanced ovarian cancer: A single center experience
Presenter: Pushpendra Hirapara
Session: Poster Display
Resources:
Abstract