Author：Qian Zhan, Dandan Ren, Beibei Mao, Xue Song, Yanna Ma, Henghui Zhang, Baiyong Shen

Background: Pancreatic cancer is one of the most aggressive human malignancies and has a poor prognosis. Large-scale studies have reported on its initiation, progression, diagnosis and prognosis. However, over the past several decades, the overall 5-year survival rate of pancreatic cancer has remained at less than 5%. Thus, the current major challenge in the postoperative management of pancreatic cancer is to identify high-risk recurrent patients. We retrospectively investigated the clinical, pathological and outcome data for 48 pancreatic cancer patients to clarify the associations of molecular mechanisms and prognosis. 

Methods: Eligible pancreatic cancer patients were included, and formalin-fixed paraffin-embedded (FFPE) tumor specimens and matched blood samples were collected at Ruijin Hospital, Shanghai Jiao tong University School of Medicine. Genome profiles were analyzed by using a designed 1408-gene panel based on next-generation sequencing (NGS). The copy number instability (CNI) score in primary tumor tissue was calculated to investigate the relationship between molecular features of the primary tumor and prognosis. 

Results: The CNI score in primary tumor tissue was positively correlated with lymph node metastasis, TP53 mutation, and early recurrence. Moreover, preoperative Carbohydrate antigen 19-9 (CA19-9) levels and CNI scores in primary tumor tissue were significant independent predictors associated with PFS in pancreatic ductal adenocarcinoma (PDAC). Finally, we performed an independent signature that includes CNI score and Carbohydrate antigen 19-9 (CA19-9) level to predict prognosis of pancreatic cancer. 

Conclusions: These results suggest that CNI score in primary tumor tissue is an independent predictive prognostic biomarker for PDAC. CNI combined with CA19-9 is a better predictor for postoperative prognostic prediction of pancreatic cancer.