Oncotarget

Research Papers:

MAP17 (PDZK1IP1) and pH2AX are potential predictive biomarkers for rectal cancer treatment efficacy

Maria Rivero, Javier Peinado-Serrano, Sandra Muñoz-Galvan, Asuncion Espinosa-Sánchez, Elisa Suarez-Martinez, Blanca Felipe-Abrio, Maria Carmen Fernández-Fernández, Maria Jose Ortiz and Amancio Carnero _

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Oncotarget. 2018; 9:32958-32971. https://doi.org/10.18632/oncotarget.26010

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Abstract

Maria Rivero1,2,4,*, Javier Peinado-Serrano1,2,3,*, Sandra Muñoz-Galvan1,3, Asuncion Espinosa-Sánchez1, Elisa Suarez-Martinez1, Blanca Felipe-Abrio1,3, Maria Carmen Fernández-Fernández1,4, Maria Jose Ortiz1,2 and Amancio Carnero1,3

1Instituto de Biomedicina de Sevilla, HUVR, CSIC, Universidad de Sevilla, Seville, Spain

2Department of Radiation Oncology, HUVR, Seville, Spain

3CIBER de Cáncer, ISCIII, Madrid, Spain

4Department of Pathology, HUVR, Seville, Spain

*These authors contributed equally to this work

Correspondence to:

Amancio Carnero, email: acarnero-ibis@us.es

Keywords: MAP17; colorectal cancer; biomarkers

Received: June 13, 2018     Accepted: July 13, 2018     Published: August 31, 2018

ABSTRACT

Rectal cancer represents approximately 10% of cancers worldwide. Preoperative chemoradiotherapy increases complete pathologic response and local control, although it offers a poor advantage in survivorship and sphincter saving compared with that of radiotherapy alone. After preoperative chemoradiotherapy, approximately 20% of patients with rectal cancer achieve a pathologic complete response to the removed surgical specimen; this response may be related to a better prognosis and an improvement in disease-free survival. However, better biomarkers to predict response and new targets are needed to stratify patients and obtain better response rates.

MAP17 (PDZK1IP1) is a small, 17 kDa non-glycosylated membrane protein located in the plasma membrane and Golgi apparatus and is overexpressed in a wide variety of human carcinomas. MAP17 has been proposed as a predictive biomarker for reactive oxygen species, ROS, inducing treatments in cervical tumors or laryngeal carcinoma. Due to the increase in ROS, MAP17 is also associated with the marker of DNA damage, phosphoH2AX (pH2AX). In the present manuscript, we examined the values of MAP17 and pH2AX as surrogate biomarkers of the response in rectal tumors. MAP17 expression after preoperative chemoradiotherapy is able to predict the response to chemoradiotherapy, similar to the increase in pH2AX. Furthermore, we explored whether we can identify molecular targeted therapies that could help improve the response of these tumors to radiotherapy. In this sense, we found that the inhibition of DNA damage with olaparib increased the response to radio- and chemotherapy, specifically in tumors with high levels of pH2AX and MAP17.


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