Mao Jia-Ding, Wu Pei, Yang Ying-Lin, Wu Jian, Huang He
Department of General Surgery, The First Affiliated Yijishan Hospital of Wannan Medical College, Wuhu 241001, Anhui Province, China.
World J Gastroenterol. 2008 May 14;14(18):2802-9. doi: 10.3748/wjg.14.2802.
To explore the correlation between the mRNAs and protein expression of gastrin (GAS), somatostatin (SS) and apoptosis index (AI), apoptosis regulation gene Fas/FasL and caspases in large intestinal carcinoma (LIC).
Expression of GAS and SS mRNAs were detected by nested RT-PCR in 79 cases of LIC. Cell apoptosis was detected by molecular biology in situ apoptosis detecting methods (TUNEL). Immunohistochemical staining for GAS, SS, Fas/FasL, caspase-3 and caspase-8 was performed according to the standard streptavidin-biotin-peroxidase (S-P) method.
There was a significant positive correlation between mRNA and protein expression of GAS and SS (GASrs = 0.99, P < 0.01; SSrs = 0.98, P < 0.01). There was significant difference in positive expression rates of GAS, SS mRNAs and protein among different histological differentiation, histological types and Dukes' stage of LIC. The AI in GAS high and moderate expression groups was significantly lower than that in low expression groups (3.75 +/- 2.38 vs 7.82 +/- 2.38, P < 0.01; 5.51 +/- 2.66 vs 7.82 +/- 2.38, P < 0.01), and the AI in SS high and moderate expression groups was significantly higher than that in low expression groups (9.03 +/- 1.76 vs 5.35 +/- 3.00, P < 0.01; 7.44 +/- 2.67 vs 5.35 +/- 3.00, P < 0.01). There was a significant negative correlation between the integral ratio of GAS to SS and the AI (r(s) = -0.41, P < 0.01). The positive expression rate of FasL in GAS high and moderate expression groups was higher than that in low expression group (90.9% and 81.0% vs 53.2%, P < 0.05). The positive expression rates of Fas, caspase-8 and caspase-3 in SS high (90.0%, 90.0% and 100%) and moderate (80.0%, 70.0%, 75.0%) expression groups were higher than that in low expression group (53.1%, 42.9%, 49.0%) (90.0% and 80.0% vs 53.1%, P < 0.05; 90.0% and 70.0% vs 42.9%, P < 0.05; 100.0% and 75.0% vs 49.0%, P < 0.05). There was a significant positive correlation between the integral ratio of GAS to SS and the semiquantitative integral of FasL (rs = 0.32, P < 0.01).
GAS and SS play important roles in the regulation and control of cell apoptosis in LIC, and the mechanism may be directly related to the aberrant expression of Fas/FasL. The GAS and SS will be valuable targets of the biological behavior of LIC.
探讨大肠癌中胃泌素（GAS）、生长抑素（SS）的mRNA与蛋白表达及凋亡指数（AI）、凋亡调控基因Fas/FasL和半胱天冬酶之间的相关性。
采用巢式逆转录-聚合酶链反应（nested RT-PCR）检测79例大肠癌组织中GAS和SS的mRNA表达。采用原位凋亡检测方法（TUNEL）进行细胞凋亡检测。按照标准链霉亲和素-生物素-过氧化物酶（S-P）法进行GAS、SS、Fas/FasL、半胱天冬酶-3和半胱天冬酶-8的免疫组织化学染色。
GAS和SS的mRNA与蛋白表达呈显著正相关（GAS相关系数rs = 0.99，P < 0.01；SS相关系数rs = 0.98，P < 0.01）。不同组织学分化程度、组织学类型及Dukes分期的大肠癌组织中，GAS、SS的mRNA及蛋白阳性表达率差异有统计学意义。GAS高表达组和中表达组的AI显著低于低表达组（3.75±2.38比7.82±2.38，P < 0.01；5.51±2.66比7.82±2.38，P < 0.01），SS高表达组和中表达组的AI显著高于低表达组（9.03±1.76比5.35±3.00，P < 0.01；7.44±2.67比5.35±3.00，P < 0.01）。GAS与SS的积分比值与AI呈显著负相关（rs = -0.41，P < 0.01）。GAS高表达组和中表达组FasL的阳性表达率高于低表达组（90.9%和81.0%比53.2%，P < 0.05）。SS高表达组（90.0%、90.0%和100%）和中表达组（80.0%、70.0%、75.0%）Fas、半胱天冬酶-8和半胱天冬酶-3的阳性表达率高于低表达组（53.1%、42.9%、49.0%）（90.0%和80.0%比53.1%，P < 0.05；90.0%和70.0%比42.9%，P < 0.05；100.0%和75.0%比49.0%，P < 0.05）。GAS与SS的积分比值与FasL的半定量积分呈显著正相关（rs = 0.32，P < 0.01）。
GAS和SS在大肠癌细胞凋亡调控中起重要作用，其机制可能与Fas/FasL的异常表达直接相关。GAS和SS将是大肠癌生物学行为的有价值靶点。
