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©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
Interaction of arylsulfatases A and B with maspin: A possible explanation for dysregulation of tumor cell metabolism and invasive potential of colorectal cancer
Zsolt Kovacs, Ioan Jung, Krisztina Szalman, Laura Banias, Tivadar Jr Bara, Simona Gurzu
Zsolt Kovacs, Ioan Jung, Laura Banias, Simona Gurzu, Department of Pathology, University of Medicine, Pharmacy, Sciences and Technology “George Emil Palade”, Targu Mures 530149, Romania
Krisztina Szalman, Department of Internal Medicine, University of Medicine, Pharmacy, Sciences and Technology “George Emil Palade”, Targu Mures 530149, Romania
Tivadar Jr Bara, Department of Surgery, University of Medicine, Pharmacy, Science and Technology “George Emil Palade”, Tirgu Mures 530149, Romania
Simona Gurzu, Research Center (CCAMF), University of Medicine, Pharmacy, Sciences and Technology, Targu Mures 540139, Romania
Author contributions: Kovacs Z drafted the article and contributed to the gene expression study; Jung I and Banias L contributed to the diagnosis and immunohistochemical assessment; Bara TJ contributed to the surgical interventions; Szalman K contributed to selection of patients for blood analysis; Gurzu S designed research and confer the final agreement for publication; Zsolt Kovacs and Krisztina Szalman have equally contribution to the paper.
Supported by the Romanian National Authority for Scientific Research, CNCSIS - UEFISCDI, No. 20 PCCF/2018.
Institutional review board statement: The Ethical Approval of Mures County Emergency Hospital and signed informed consent was obtained before surgery.
Conflict-of-interest statement: All authors have no conflicts of interest.
CONSORT 2010 statement: The guidelines of the CONSORT 2010 Statement have been adopted.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Simona Gurzu, MD, PhD, Professor, Department of Pathology, University of Medicine, Pharmacy, Sciences and Technology, “George Emil Palade”, 38 Gheorghe Marinescu Street, Targu Mures 540139, Romania. simonagurzu@yahoo.com
Telephone: +40-745-673550 Fax: +40-265-210407
Received: September 27, 2019
Peer-review started: September 27, 2019
First decision: October 24, 2019
Revised: October 31, 2019
Accepted: November 15, 2019
Article in press: November 15, 2019
Published online: December 6, 2019
BACKGROUND
Although it has been shown that arylsulfatases are lost in colorectal cancer (CRC) cell lines, their exact role in the carcinogenesis and behavior of this cancer was not elucidated. No data about the correlation between serum and immunohistochemical (IHC) level of arylsulfatases (ARSA, ARSB) in patients with CRC were published yet.
AIM
To evaluate the possible prognostic value of ARSA and/or ARSB in CRC, at circulating and protein levels.
METHODS
The present study included 45 consecutive patients who were prospectively diagnosed with CRC. For IHC stains (protein expression) ARSA, ARSB and maspin expression were quantified. For these markers, cytoplasmic expression was taken into account. For gene expression study, circulating mRNA was isolated from all patients, before surgery. A group of 45 healthy patients without inflammatory or tumor pathologies was used as control group. Reverse transcription and Taqman Gene Expression Array were used for ARSB gene expression.
RESULTS
The preoperative circulating RNA level of the ARSB gene was significantly decreased in patients with CRC (RQ < 1), compared with the control group (RQ > 1). A more significant decrease (RQ < 0.5) occurred in ulcero-infiltrative maspin-positive adenocarcinomas, with a higher degree of tumor budding, diagnosed in locally advanced stages (pT3/4). ARSA/maspin immunopositivity indicated a higher risk for lymph node metastasis, while triple positivity for maspin/ARSA/ARSB and ARSB gene expression level < 0.5 were indicators of CRC aggressive behavior, independent of lymph node status.
CONCLUSION
The significant independent negative prognostic factors of CRC are the ulcero-infiltrative aspect, high budding degree, triple positivity for maspin, ARSA and ARSB, and low ARSB gene expression.
Core tip: In this paper we tried to emphasize the role of arylsulfatases (ARSA, ARSB) in colorectal cancer (CRC) beahaviour and possible role of ARSB serum level in follow-up of patients. This is the first study in literature which proved that a low ARSB gene expression in serum (RQ < 1) might be a non-invasive indicator of risk of CRC. Moreover, triple positivity for maspin/ARSA/ARSB and ARSB gene expression level < 0.5 were proved to be indicators of CRC aggressive behavior, independent of lymph node status.
