Kovacs Zsolt, Jung Ioan, Szalman Krisztina, Banias Laura, Bara Tivadar Jr, Gurzu Simona
Department of Pathology, University of Medicine, Pharmacy, Sciences and Technology "George Emil Palade", Targu Mures 530149, Romania.
Department of Internal Medicine, University of Medicine, Pharmacy, Sciences and Technology "George Emil Palade", Targu Mures 530149, Romania.
World J Clin Cases. 2019 Dec 6;7(23):3990-4003. doi: 10.12998/wjcc.v7.i23.3990.
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.
To evaluate the possible prognostic value of ARSA and/or ARSB in CRC, at circulating and protein levels.
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 gene expression.
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 gene expression level < 0.5 were indicators of CRC aggressive behavior, independent of lymph node status.
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.
尽管已经表明芳基硫酸酯酶在结直肠癌(CRC)细胞系中缺失,但其在该癌症的致癌作用及行为中的确切作用尚未阐明。关于CRC患者血清和芳基硫酸酯酶(ARSA、ARSB)免疫组化(IHC)水平之间相关性的数据尚未发表。
评估ARSA和/或ARSB在循环和蛋白质水平对CRC的可能预后价值。
本研究纳入了45例前瞻性诊断为CRC的连续患者。对IHC染色(蛋白质表达)进行ARSA、ARSB和组织蛋白酶抑制剂maspin表达定量。对于这些标志物,考虑细胞质表达。对于基因表达研究,在手术前从所有患者中分离循环mRNA。选取45例无炎症或肿瘤病变的健康患者作为对照组。采用逆转录和Taqman基因表达阵列进行基因表达分析。
与对照组(RQ>1)相比,CRC患者术前ARSB基因的循环RNA水平显著降低(RQ<1)。在局部晚期(pT3/4)诊断的具有较高肿瘤芽生程度的溃疡浸润性maspin阳性腺癌中下降更为显著(RQ<0.5)。ARSA/maspin免疫阳性表明淋巴结转移风险较高,而maspin/ARSA/ARSB三联阳性且基因表达水平<0.5是CRC侵袭性行为的指标,与淋巴结状态无关。
CRC的显著独立阴性预后因素是溃疡浸润性表现、高芽生程度、maspin、ARSA和ARSB三联阳性以及低ARSB基因表达。