Abstract
INTRODUCTION: Clinical decision-making is challenging in patients who undergo cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) when complete cytoreduction is not feasible. Nevertheless, some patients still benefit with long-term survival after incomplete CRS/HIPEC. There is currently no robust predictive tool that can assist clinical decision-making in this setting. METHODS: We quantified gene expression of 79 appendiceal mucinous neoplasms (AMN) from patients with incomplete CRS/HIPEC (R2 resection) using a custom NanoString gene panel. Using our previously defined, prognostic subtype classification algorithm based on signed nonnegative matrix factorization, we classified AMN cases into three molecular subtypes termed: immune enriched (IE), mixed (M), and oncogene enriched (OE). Kaplan-Meier and Cox proportional hazards analyses were used to associate subtypes and individual genes with overall survival (OS). RESULTS: Median overall survival (OS) was 7.7 years for IE, 3.6 years for M, and 1.4 years for OE. Compared with IE, OE was associated with significantly lower survival [hazard ratio (HR) 3.64, 95% confidence interval (CI) 1.63-8.13; p = 0.0017]. The differences were observed in both low-grade and high-grade tumors. While only two genes were identified to be associated with OS in low-grade tumors, multiple genes were identified to be associated with OS in high-grade tumors, particularly genes with functions in cell cycle/proliferation, mucin production, immune pathways, and cell adhesion/migration. CONCLUSION: Genetic signatures have prognostic value in patients with incomplete cytoreduction and provide valuable information to assist clinical and operative decision-making. Unraveling genetic alterations and involved pathways can direct efforts to design novel therapeutic modalities.