Venerito M, Helmke C, Jechorek D, Wex T, Rosania R, Antweiler K, Weigt J, Malfertheiner P
Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Leipziger Str. 44, 39120, Magdeburg, Germany.
Institute of Pathology, Otto-von-Guericke University Hospital, Leipziger Str. 44, 39120, Magdeburg, Germany.
BMC Gastroenterol. 2016 Jul 30;16(1):85. doi: 10.1186/s12876-016-0499-z.
Leukotriene B4 (LTB4R and LTB4R2) and cysteinyl leukotriene receptors (CYSLTR1 and CYSLTR2) contribute to malignant cell transformation. We aimed to investigate the expression of LTB4R, LTB4R2, CYSLTR1 and CYSLTR2 in esophageal squamous cell carcinoma and adjacent non-transformed squamous epithelium of the esophagus, as well as in control biopsy samples from esophageal squamous epithelium of patients with functional dyspepsia.
Expression of LTB4R, LTB4R2, CYSLTR1 and CYSLTR2 was analyzed by immunohistochemistry (IHC) and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in biopsy samples of 19 patients with esophageal squamous cell cancer and 9 sex- and age-matched patients with functional dyspepsia.
LTB4R, LTB4R2, CYSLTR1 and CYSLTR2 were expressed in all biopsy samples. Major findings were: 1) protein levels of all leukotriene receptors were significantly increased in esophageal squamous cell cancer compared to control mucosa (p < 0.05); 2) CYSLTR1 and CYSLTR2 gene expression was decreased in cancer tissue compared to control at 0.26-fold and 0.23-fold respectively; 3) an up-regulation of LTB4R (mRNA and protein expression) and a down-regulation of CYSLTR2 (mRNA expression) in non-transformed epithelium of cancer patients compared to control (p < 0.05) was observed.
The expression of leukotriene receptors was deregulated in esophageal squamous cell cancer. Up-regulation of LTB4R and down-regulation of CYSLTR2 gene expression may occur already in normal squamous esophageal epithelium of patients with esophageal cancer suggesting a potential role of these receptors in early steps of esophageal carcinogenesis. Larger studies are warranted to confirm these observations.
白三烯B4（LTB4R和LTB4R2）以及半胱氨酰白三烯受体（CYSLTR1和CYSLTR2）与恶性细胞转化有关。我们旨在研究LTB4R、LTB4R2、CYSLTR1和CYSLTR2在食管鳞状细胞癌、癌旁未转化的食管鳞状上皮以及功能性消化不良患者食管鳞状上皮对照活检样本中的表达情况。
采用免疫组织化学（IHC）和定量逆转录聚合酶链反应（qRT-PCR）分析19例食管鳞状细胞癌患者及9例年龄和性别匹配的功能性消化不良患者活检样本中LTB4R、LTB4R2、CYSLTR1和CYSLTR2的表达。
所有活检样本中均表达LTB4R、LTB4R2、CYSLTR1和CYSLTR2。主要发现如下：1）与对照黏膜相比，食管鳞状细胞癌中所有白三烯受体的蛋白水平均显著升高（p < 0.05）；2）与对照相比，癌组织中CYSLTR1和CYSLTR2基因表达分别下降至0.26倍和0.23倍；3）与对照相比，癌患者未转化上皮中LTB4R（mRNA和蛋白表达）上调，CYSLTR2（mRNA表达）下调（p < 0.05）。
食管鳞状细胞癌中白三烯受体表达失调。食管癌患者正常食管鳞状上皮中可能已出现LTB4R上调和CYSLTR2基因表达下调，提示这些受体在食管癌发生早期可能发挥潜在作用。需要更大规模的研究来证实这些观察结果。
