Photo Credit: Silver Place
The following is a summary of “Development and Validation of the Predictive and Prognostic ChemoResist Signature in Resected Pancreatic Ductal Adenocarcinoma: Multicenter Study,” published in the December 2024 issue of Surgery by Huang et al.
Pancreatic ductal adenocarcinoma (PDAC) is highly heterogeneous and exhibits varied responses to treatment.
Researchers conducted a retrospective study to develop and validate a predictive and prognostic signature for patients with PDAC undergoing resection and chemotherapy.
They examined genetic mutations in the 4 most common PDAC genes and 12 PI3K/AKT/mTOR pathway markers in 551 patients from 3 tertiary centers. A predictive signature, ChemoResist, was developed using a least absolute shrinkage and selection operator (LASSO) Cox regression model, incorporating genetic and clinicopathologic data and validated in independent cohorts.
The results showed that the ChemoResist signature, based on Kirsten rat sarcoma viral oncogene homolog (KRAS) single nucleotide variation (SNV), phosphatase and tensin homolog (PTEN), mechanistic target of rapamycin (mTOR) expressions, and 6 clinicopathologic features, significantly predicted survival outcomes. Patients with high and low ChemoResist scores showed median OS differences in both training (17 vs. 42 months, P<0.001) and validation cohorts (18 vs. 35 months, P=0.034). Median disease-free survival (DFS) was also significantly different (training: 10 vs. 23 months, P<0.001; validation: 11 vs. 20 months, P=0.028). The signature was an independent predictive factor and showed better prediction accuracy for 2-year OS compared to tumor, node, metastasis (TNM) stage, and other clinicopathologic factors (AUC 0.788 vs. 0.636, P<0.001). Patients with low ChemoResist scores showed a better response to adjuvant chemotherapy (HR for OS: training, 0.22 vs. 0.57; validation, 0.26 vs. 0.50; HR for DFS: training, 0.35 vs. 0.54; validation, 0.18 vs. 0.59).
They concluded that the ChemoResist signature accurately predicted survival and chemotherapy response in patients with PDAC undergoing resection, outperforming the TNM stage and other clinicopathologic factors.
