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
164P - Neoadjuvant immune checkpoints inhibitors plus chemoradiotherapy for patients with locally advanced esophageal squamous cell carcinoma
Presenter: Ming-Wei Kao
Session: Poster Display
Resources:
Abstract
165P - BMI impact on the prognosis of unresectable HCC patients receiving first-line lenvatinib or atezolizumab plus bevacizumab
Presenter: Elisabeth Amadeo
Session: Poster Display
Resources:
Abstract
166P - Preoperative risk factors strongly related to early recurrence after R0 resection of gallbladder cancer
Presenter: SANGHUN LEE
Session: Poster Display
Resources:
Abstract
167P - Peripheral blood neutrophil-to-lymphocyte ratio correlated with serum IL-8 level and predict the outcome of hepatocellular carcinoma patients treated with immune-targeted combination therapy
Presenter: Xuenan Peng
Session: Poster Display
Resources:
Abstract
168P - Real-world clinicopathological characteristics and treatment patterns of esophageal cancer patients in China
Presenter: Zhihao Lu
Session: Poster Display
Resources:
Abstract
169P - Conversion response and prognostic factors in HCC patients with macrovascular invasion treated with atezolizumab plus bevacizumab
Presenter: xiaodong Zhu
Session: Poster Display
Resources:
Abstract
170P - Atezolizumab plus bevacizumab (A+B) versus lenvatinib for BCLC-B stage of patients with hepatocellular carcinoma (HCC): A large real-life worldwide population
Presenter: Francesco Vitiello
Session: Poster Display
Resources:
Abstract
171P - Retrospective study of the correlation between proteinuria and renal function in patients (pts) with unresectable hepatocellular carcinoma (uHCC) treated with atezolizumab plus bevacizumab (Atezo+Bev): ARISE study
Presenter: Kazuomi Ueshima
Session: Poster Display
Resources:
Abstract
172P - Trastuzumab deruxtecan (T-DXd) in Chinese patients (pts) with previously treated HER2-positive locally advanced/metastatic gastric cancer (GC) or gastroesophageal junction adenocarcinoma (GEJA): Primary efficacy and safety from the phase II single-arm DESTINY-Gastric06 (DG06) trial
Presenter: Zhi Peng
Session: Poster Display
Resources:
Abstract
173P - Lenvatinib (L) versus sorafenib (S) second-line therapy in hepatocellular carcinoma (HCC) patients progressed to atezolizumab plus bevacizumab (AB)
Presenter: Mara Persano
Session: Poster Display
Resources:
Abstract