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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
ARTICLE HIGHLIGHTS
Research background
Arylsulfatase A and B (ARSA, ARSB) are lysosomal enzymes playing an important role in cellular metabolism. It is described in the literature the genetic condition characterized by a total deficiency of these two enzymes but few aspects are known about their role in carcinogenesis and evolution of colorectal cancer (CRC).
Research motivation
As no data about the correlation of ARSA, ARSB and maspin were published yet, this study is original and represents first step in understanding the arylsulfatases influence upon malignant cells.
Research objectives
This paper aimed to compare the immunohistochemical (IHC) stain and gene expression profile of ARSA and ARSB in CRC. Correlation with maspin and classical clinicopathological parameters was also done.
Research methods
For IHC study, the expression of ARSA, ARSB and maspin were quantified in the cytoplasm of CRC cells. For gene expression study circulating mRNA, using Roche HighPure RNA kit, was isolated from all patients before surgery. A group of 45 healthy patients without inflammatory or tumor pathologies was used as a control group. Reverse transcription and Taqman Gene Expression Array were used for Arylsulfatase B gene expression. Statistical analysis was performed using GraphPad Prims8 software using the χ2 and Kruskal-Wallis test, while the Mann-Whitney test was used for ARSB gene expression, considering a P-value < 0.05 (with a 95% confidence interval) statistically significant.
Research results
The preoperative gene expression level of ARSB 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 (T3/4). The ARSB protein level in surgical specimens was inversely correlated with the preoperative ARSB gene circulating level.
Research conclusions
High IHC expression of ARSA and ARSB, correlated with maspin positivity can be used as indicators of prognosis of CRC. Triple positivity of ARSA/ARSB/maspin correlated with an ARSB gene circulating level of <0.5, is an indicator of a lower survival rate, independently of the other clinicopathological parameters.
Research perspectives
Based on the high IHC and low gene expression of ARSB, further investigations should be done, to elucidate the precise mechanism of this contradictory protein-gene expression profile.
