Published online Dec 6, 2019. doi: 10.12998/wjcc.v7.i23.3990
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
Processing time: 69 Days and 19.4 Hours
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).
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.
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.
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.
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.
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.
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.