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

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 met...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6646658/
https://www.ncbi.nlm.nih.gov/pubmed/31332257
http://dx.doi.org/10.1038/s41598-019-46819-z
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author 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
author_facet 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
author_sort Shannon, Nicholas Brian
collection PubMed
description 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.
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spelling pubmed-66466582019-07-29 A set of molecular markers predicts chemosensitivity to Mitomycin-C following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastasis 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 Sci Rep Article 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. Nature Publishing Group UK 2019-07-22 /pmc/articles/PMC6646658/ /pubmed/31332257 http://dx.doi.org/10.1038/s41598-019-46819-z Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
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
A set of molecular markers predicts chemosensitivity to Mitomycin-C following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastasis
title A set of molecular markers predicts chemosensitivity to Mitomycin-C following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastasis
title_full A set of molecular markers predicts chemosensitivity to Mitomycin-C following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastasis
title_fullStr A set of molecular markers predicts chemosensitivity to Mitomycin-C following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastasis
title_full_unstemmed A set of molecular markers predicts chemosensitivity to Mitomycin-C following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastasis
title_short A set of molecular markers predicts chemosensitivity to Mitomycin-C following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastasis
title_sort set of molecular markers predicts chemosensitivity to mitomycin-c following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastasis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6646658/
https://www.ncbi.nlm.nih.gov/pubmed/31332257
http://dx.doi.org/10.1038/s41598-019-46819-z
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