Abstract 25P
Background
Stage II CC demonstrates intra-stage variability in outcomes. Predictive and prognostic value of current biomarkers for guiding treatment of stage II CC is limited. We aimed to develop a prognostic transcriptional signature for high-risk stage II CC patients undergoing adjuvant chemotherapy (ACT) with either 3 or 6 months of FOLFOX/CAPOX in the TOSCA trial.
Methods
Observational retrospective study based on the TOSCA trial database, matching 62 patients with high-risk stage II CC who relapsed with 62 who did not. Matching criteria included the recruitment centers, pT stage, type and duration of ACT treatment. Transcriptome sequencing was conducted on FFPE blocks. The generated data were processed using the nf-core/rnaseq pipeline (v 3.14.0) and analyzed for differential gene expression, requiring a minimum absolute log fold change of 1 and a false discovery rate (FDR) < 0.1. The impact of microsatellite instability (MSI) vs MSS, 3 vs 6 months, and XELOX vs FOLFOX were evaluated.
Results
Out of 124 stage II CC cases, 72 were of sufficient quality for RNA sequencing and were included in the analysis. The median age was 63 (IQR 55-71), 40% were right-sided, 59% received FOLFOX, 54% received 3 months of ACT, and 19% were MSI. We identified a signature among the top 17 differentially expressed genes (absolute log fold-change > 1, p-value < 0.001, FDR < 0.1, see Table). Patients exhibiting a worse prognostic signature (PROSIT-L) showed shorter disease-free survival (DFS) compared to those with a better prognostic signature (PROSIT-H) (HR 3.5; 95% CI 1.5 – 7.9; p .002). No significant interaction was observed based on MSI status, or type and duration of treatment. Table: 25P
| Gene | log2FoldChange |
| DNAH11 | 2,5 |
| PTCHD4 | 2,4 |
| TMPRSS13 | 1,4 |
| SMOC2 | 1,3 |
| KIAA1683 | -1 |
| HHEX | -1 |
| PLLP | -1,2 |
| CD22 | -1,3 |
| CACNG8 | -1,3 |
| LYZ | -1,4 |
| CLSTN2 | -1,5 |
| CD27 | -1,5 |
| BARX2 | -1,6 |
| UGT1A6 | -1,6 |
| FAM129C | -1,6 |
| SLC6A14 | -2,1 |
| CTSE | -2,9 |
Conclusions
We have identified a transcriptomic signature with strong and independent prognostic value, regardless of the treatment and MSI status. This new transcriptomic signature may identify stage II CC patients who are likely to relapse despite receiving oxaliplatin-based ACT.
Legal entity responsible for the study
The authors.
Funding
AIRC GRANT IG 2018.
Disclosure
All authors have declared no conflicts of interest.