A set of molecular markers predicts chemosensitivity to Mitomycin-C following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastasis.

ABSTRACT: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with significant perioperative morbidity and mortality. We aim to generate and validate a biomarker set predicting sensitivity to Mitomycin-C to refine selection of patients with colorectal peritoneal metastasis (CPM) for this treatment. A signature predicting Mitomycin-C sensitivity was generated using data from Genomics of Drug Sensitivity in Cancer and The Cancer Genome Atlas. Validation was performed on CPM patients who underwent CRS-HIPEC (n?=?62) using immunohistochemistry (IHC). We determined predictive significance of our set using overall survival as a surrogate endpoint via a logistic regression model. Three potential biomarkers were identified and optimized for IHC. Patients exhibiting lower expression of PAXIP1 and SSBP2 had poorer survival than those with higher expression (p?=?0.045 and 0.140, respectively). No difference was observed in patients with differing DTYMK expression (p?=?0.715). Combining PAXIP1 and SSBP2 in a set, patients with two dysregulated protein markers had significantly poorer survival than one or no dysregulated marker (p?=?0.016). This set independently predicted survival in a Cox regression model (HR 5.097; 95% CI 1.731-15.007; p?=?0.003). We generated and validated an IHC prognostic set which could potentially identify patients who are likely to benefit from HIPEC using Mitomycin-C.

SUBMITTER: Shannon NB 

PROVIDER: S-EPMC6646658 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature