Risk Stratification and Prognosis Determination Based on Protein Lysine Crotonylation in Patients with Resected Pancreatic Cancer: A Multicenter Study.

PURPOSE

Despite advances in neoadjuvant therapy and surgery, a limited increase in the 5-year survival rate of patients with pancreatic ductal adenocarcinoma (PDAC) has occurred, implying the importance of postoperative management. This study aims to achieve risk stratification of patients with PDAC, providing guidance for clinicians to make better regimen choices and realizing precision treatment.

EXPERIMENTAL DESIGN

Five protein posttranslational modifications (PTM) were detected to find out the most prognostic marker using the IHC method. The predictive and prognostic performance of lysine pan-crotonylation (pan-Kcr) expression standing out from the initial selection was measured in the discovery cohort and validated in two independent cohorts. A risk stratification model was constructed based on pan-Kcr expression.

RESULTS

A total of 309 (93, 114, and 102 from Qingdao, Tianjin, and Jilin cohorts, respectively) patients with PDAC were included. Pan-Kcr expression was the only significantly deregulated PTM between cancer and its paracancerous tissues. The low pan-Kcr level was an independent predictive (HR, 0.470; P = 0.0090) and prognostic (HR, 0.312; P < 0.0001) marker for patients with PDAC. We constructed a risk-stratification model based on pan-Kcr expression, and high-risk patients suffered a significantly shorter disease-free survival and overall survival (median disease-free survival, 5 vs. 12.5; P < 0.0001; median overall survival, 7 vs. 24; P < 0.0001). The model was well validated in two independent cohorts.

CONCLUSIONS

Pan-Kcr is an independent predictive and prognostic marker for resected patients with PDAC. The risk stratification could provide guidance for clinicians to make precision regimen choices. Also, our findings illustrated the feasibility of PTM-guided prognosis and biomarker-aided PDAC adjuvant therapy.