Genomic and transcriptomic alterations associated with therapy response and prognosis in patients with peritoneal metastases undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) are considered to treat peritoneal metastasis (PM) from various origins. However, patient selection for this procedure relying on conventional prognostic factors is not yet optimal. In this study, we aimed to explore the tumor molecular characteristics in patients’ pretreatment tissues at genomic and transcriptomic level, which could be of great value for prognosis and contribute to the repertoire of therapeutic targets for PM management.
Methods: Blood and tumor samples were collected from patients with PM before HIPEC. Whole exome sequencing (WES) and transcriptome sequencing (RNA-seq) were performed to determine the tumor molecular profiles in each patient. After treatment, patient cohort was divided into responders and non-responders according to 12-month progression-free survival (PFS). Comparisons regarding characteristics between two cohorts were carried out to identify potential targets.
Results: A total of 15 patients with PM were enrolled in this study. Patients with relapse within 12 months after CRS/HIPEC had significantly poorer prognosis than their counterparts (p = 0.015). Driver genes and enriched pathways were identified from the WES data. Importantly, AGAP5 gene was found selectively mutated in the responders and significantly associated with better overall survival (OS) (p = 0.00652). At transcriptomic level, gene expression levels of five differentially expressed genes between non-responders and responders (i.e., RPL27, LGI4, DUSP15, PTCH2 and OPN3) were significantly associated with OS. These findings may help predict therapy response and patient outcome.
Conclusions: Our study provides identified prognostic markers in PM tumor biology to facilitate decision-making before CRS/HIPEC.