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- Title
A set of molecular markers predicts chemosensitivity to Mitomycin-C following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastasis.
- Authors
Shannon, Nicholas Brian; Tan, Joey Wee-Shan; Tan, Hwee Leong; Wang, Weining; Chen, Yudong; Lim, Hui Jun; Tan, Qiu Xuan; Hendrikson, Josephine; Ng, Wai Har; Loo, Li Yang; Skanthakumar, Thakshayeni; Wasudevan, Seettha D.; Kon, Oi Lian; Lim, Tony Kiat Hon; Tan, Grace Hwei Ching; Chia, Claramae Shulyn; Soo, Khee Chee; Ong, Chin-Ann Johnny; Teo, Melissa Ching Ching
- 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.
- Publication
Scientific Reports, 2019, Vol 9, Issue 1, pN.PAG
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-019-46819-z