Genetic alterations and tumor mutation burden predict chemosensitivity of pancreatic cancer: a retrospective study

Background: Chemotherapy stands as a recommended approach for all stages of pancreatic cancer. However, its efficacy stratification remains obscure. Genomic sequencing is extensively applied across diverse diseases. This study aims to explore the potential genomic markers in relation to the decision-making of chemotherapy. Methods: A total of 140 patients with pancreatic cancer were categorized into chemotherapy-first group and adjuvant chemotherapy group. The genomic alterations were detected from the next-generation sequencing using surgical or fine-needle-biopsy specimens. Chemotherapy response was defined according to objective response based on the RECIST criteria (version 1.1). Results: In the chemotherapy-first group, the patients who harbored higher TMB levels had significant shorter PFS than that with low TMB levels (Hazard ratio [HR] = 30.362, P = 0.002). No independent risk factors were found to be correlated with chemoresistance in patients receiving chemotherapy at first (all P > 0.05). In the adjuvant chemotherapy group, the increased CA125 level of more than 35 U/mL potentially elucidated a shorter period of DFS (HR = 3.695, P = 0.020). Conclusion: Our study indicated that a high level of TMB may predict earlier tumor progression in pancreatic cancer patients received chemotherapy at first. The elevation of CA125 presents itself as a predictive indicator for postoperative chemotherapy patients' tumor recurrence, whereas gene mutations remain unrelated to this phenomenon.