Al-Khayal Khayal, Abdulla Maha, Al-Obeed Omar, Al Kattan Wael, Zubaidi Ahmad, Vaali-Mohammed Mansoor-Ali, Alsheikh Abdulmalik, Ahmad Rehan
Colorectal Research Chair, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Department of Surgery, College of Medicine, Al-Faisal University, Riyadh, Kingdom of Saudi Arabia.
Oncol Rep. 2016 Mar;35(3):1281-6. doi: 10.3892/or.2015.4494. Epub 2015 Dec 17.
The TP53-induced glycolysis and apoptosis regulator (TIGAR) is a p53 target gene known to regulate glycolysis by acting as fructose bis-phosphatase (FBPase) and modulate reactive oxygen species. TIGAR expression has been implicated in oncogenesis and progression of several human cancers. However, TIGAR expression is not known in various stages of colorectal cancer (CRC). There is an increase in the colorectal cancer incidence in Saudi Arabia. We sought to analyze TIGAR expression in this ethnic group. The aim of this study was to investigate the TIGAR expression in colorectal cancer (CRC) patients from Saudi Arabia. Tissue microarray (TMA) was constructed from 22 matched colorectal tumor tissues and adjacent normal tissues. TIGAR expression was examined in TMA slide using immunohistochemistry. TIGAR mRNA was determined in 14 matched tumor tissue and adjacent normal tissue. TIGAR protein expression was also examined in CRC tumor tissues and cell lines. Statistical analyses (t-test) were applied to evaluate the significance of TIGAR expression. TIGAR mRNA level was upregulated significantly in stage II (p<0.01) and stage III (p<0.05) when compared to adjacent normal tissue. Immunohistochemical studies revealed that TIGAR expression was increased in colorectal cancer. Strong TIGAR positive staining was found in 68% (15/22) of the tumor samples with nuclear localization. TIGAR staining was found to be significantly increased in early stage (stage I and II) CRC (p<0.05) and late stage (stage III and IV) CRC (p<0.01). TIGAR protein was also found to be highly expressed in stage II and III colorectal cancer tissues and CRC cell lines. These findings indicate that TIGAR is highly expressed at the mRNA and protein levels in colorectal cancer with prominent nuclear localization. TIGAR expression may be used as a bio-marker for detection of colorectal cancer and can be used as a target for developing therapeutics for the treatment of colorectal cancer.
TP53诱导的糖酵解和凋亡调节因子（TIGAR）是一种p53靶基因，已知其通过作为果糖双磷酸酶（FBPase）来调节糖酵解并调节活性氧。TIGAR表达与几种人类癌症的发生和进展有关。然而，在结直肠癌（CRC）的各个阶段中TIGAR的表达情况尚不清楚。沙特阿拉伯的结直肠癌发病率有所上升。我们试图分析该族群中TIGAR的表达情况。本研究的目的是调查沙特阿拉伯结直肠癌（CRC）患者中TIGAR的表达。从22对匹配的结直肠肿瘤组织和相邻正常组织构建组织微阵列（TMA）。使用免疫组织化学在TMA载玻片上检测TIGAR表达。在14对匹配的肿瘤组织和相邻正常组织中测定TIGAR mRNA。还在CRC肿瘤组织和细胞系中检测TIGAR蛋白表达。应用统计分析（t检验）来评估TIGAR表达的显著性。与相邻正常组织相比，TIGAR mRNA水平在II期（p<0.01）和III期（p<0.05）显著上调。免疫组织化学研究显示结直肠癌中TIGAR表达增加。在68%（15/22）的肿瘤样本中发现强TIGAR阳性染色且定位于细胞核。发现TIGAR染色在早期（I期和II期）CRC（p<0.05）和晚期（III期和IV期）CRC（p<0.01）中显著增加。还发现TIGAR蛋白在II期和III期结直肠癌组织及CRC细胞系中高表达。这些发现表明TIGAR在结直肠癌中在mRNA和蛋白水平均高表达且具有明显的细胞核定位。TIGAR表达可作为检测结直肠癌的生物标志物，并可作为开发结直肠癌治疗药物的靶点。
