ADCY7、GPR86、GRIN2D、RGS4對胃癌前病變進展的預測價值

背景：目前臨床上尚無有效預測胃癌前病變進展或篩查早期胃癌的生物學標志物。目的：研究腺苷酸環化酶7（ADCY7）、G蛋白偶聯受體GPR86、N?甲基?D?天冬氨酸離子能谷氨酸受體2D（GRIN2D）、G蛋白信號調節因子4（RGS4）在不同胃黏膜病變中的表達及其對胃癌前病變進展的預測價值。方法：應用免疫組化法、real?time PCR和蛋白質印跡法檢測ADCY7、GPR86、GRIN2D、RGS4在Correa級聯各階段（包括慢性非萎縮性胃炎、慢性萎縮性胃炎、低級別和高級別上皮內瘤變、黏膜層和黏膜下層早期胃癌）以及胃癌與相應癌旁組織間的表達差異。結果：ADCY7、GPR86、GRIN2D、RGS4在胃炎、上皮內瘤變、早期胃癌中的表達呈遞增趨勢，除GRIN2D在上皮內瘤變與早期胃癌中的表達無明顯差異外，兩兩比較差異均有統計學意義（P均lt;0.001）。GPR86、GRIN2D mRNA和蛋白在胃癌組織中的表達顯著高于癌旁gt;5 cm組織（P均lt;0.05）；RGS4蛋白在胃癌組織中的表達高于癌旁gt;5 cm組織，其mRNA表達趨勢則相反（P均lt;0.05）；ADCY7僅蛋白表達在胃癌與癌旁gt;5 cm組織間差異顯著（Plt;0.05）。結論：ADCY7、GPR86、GRIN2D、RGS4在Correa級聯各階段以及胃癌與相應癌旁組織間的表達變化提示其參與了胃癌前病變的發生、發展，可能具有預測胃癌前病變進展的價值。

關鍵詞 胃腫瘤； Correa級聯； 癌前病變； 早期胃癌； 生物學標記

ADCY7， GPR86， GRIN2D， and RGS4 for Predicting Progression of Gastric Precancerous Lesions LI Yang1， NIAN Yuanyuan2， MENG Xianmei2. 1Baotou Medical College， Inner Mongolia University of Science and Technology， Baotou， Inner Mongolia Autonomous Region （014040）; 2Department of Gastroenterology， the Second Affiliated Hospital of Baotou Medical College， Inner Mongolia University of Science and Technology， Baotou， Inner Mongolia Autonomous Region

Correspondence to： MENG Xianmei， Email： mxmxhk@163.com

Background： Currently， there are no effective biomarkers for predicting the progression of gastric precancerous lesions or screening early gastric cancer in clinical practice. Aims： To explore the expressions of adenylate cyclase 7 （ADCY7）， G protein?coupled receptor GPR86， glutamate receptor， ionotropic， N?methyl D?aspartate 2D （GRIN2D） and regulator of G protein signaling 4 （RGS4） in various gastric mucosal lesions and their predictive value for progression of gastric precancerous lesions. Methods： Expressions of ADCY7， GPR86， GRIN2D， and RGS4 were detected by immuno?histochemistry， real?time PCR and Western blotting in Correa cascade （chronic non?atrophic gastritis， chronic atrophic gastritis， low? and high?grade intraepithelial neoplasia， and mucosal and submucosal early gastric cancer） and cancerous and para?cancerous tissues， among which， the differences in expression levels of these four factors were analyzed. Results： There was an increasing tendency in expression levels of ADCY7， GPR86， GRIN2D， and RGS4 from gastritis， intra?epithelial neoplasia to early gastric cancer. Except for GRIN2D expression between intraepithelial neoplasia and early gastric cancer， significant differences could be observed in any two groups （all Plt;0.001）. Both mRNA and protein expression levels of GRP86 and GRIN2D were significantly higher in cancerous tissue than in adjacent tissue gt;5 cm （all Plt;0.05）. Protein expression of RGS4 was significantly higher in cancerous tissue than in adjacent tissue gt;5 cm， but its mRNA expression presented an opposite trend （all Plt;0.05）. Significant difference between cancerous tissue and adjacent tissue gt;5 cm in ADCY7 expression was only existed at protein level （Plt;0.05）. Conclusions： Alterations of the expression levels of ADCY7， GPR86， GRIN2D， and RGS4 in Correa cascade and cancerous and para?cancerous tissues suggest that they are involved in the occurrence and development of gastric precancerous lesions， and might be used as predictors for progression of gastric precancerous lesions.

Key words Stomach Neoplasms; Correa Cascade; Precancerous Lesions; Early Gastric Cancer; Biological Markers

據2020年全球癌癥統計數據，胃癌每年新發病例數超過108萬例，每年約有77萬人死于胃癌[1]。目前普遍認可的胃癌發生模式為Correa級聯，即慢性萎縮性胃炎（chronic atrophic gastritis， CAG）→腸化生→低級別上皮內瘤變（low?grade intraepithelial neoplasia， LGIN）→高級別上皮內瘤變（high?grade intraepithelial neoplasia， HGIN）→胃癌[2]，其中胃黏膜萎縮、腸化生、LGIN、HGIN屬于胃癌前病變[3]。胃癌前病變的進展是一個緩慢的過程，最終進展至胃癌的概率較低[4]。……