CAJ | 학술논문

背景与目的：在胃癌的发生、发展过程中，内质网应激、细胞的修复及凋亡是重要的病理生理过程，而GRP78与pERK在其中发挥了重要的作用。研究葡萄糖调节蛋白78(glucose-regulated proteins 78，GRP78)和磷酸化细胞外信号调节激酶(pERK)在胃腺癌、慢性萎缩性胃炎及浅表性胃炎组织中的表达，研究它们与胃癌发生、发展的关系。方法：RT-PCR法检测各25例胃腺癌、慢性萎缩性胃炎和浅表性胃炎新鲜组织中GRP78、pERK基因表达；免疫组化法分别检测各60例胃腺癌、慢性萎缩性胃炎和浅表性胃炎组织中GRP78、pERK蛋白表达，并分析其蛋白表达与临床病理参数间的相关性。结果：RT-PCR半定量结果显示，胃癌组织中GRP78及pERK mRNA的相对表达水平(1.26±0.18、2.35±0.36)均明显高于慢性萎缩性胃炎组织(0.89±0.25、1.18±0.25)及浅表性胃炎组织(0.29±0.09、0.68±0.10)，差异有统计学意义(P＜0.01)。免疫组织化学结果显示，GRP78及pERK蛋白在胃癌组织中的表达率(78.3%、88.3%)亦均高于慢性萎缩性胃炎(46.6%、43.3%)及浅表性胃炎组织(6.7%、5.0%)，差异有统计学意义(P＜0.01)。胃癌组织中GRP78及pERK蛋白表达与胃癌分化程度、分期、淋巴结转移等有明显相关性。GRP78及pERK基因及蛋白表达水平在胃癌中均呈正相关(基因：r=0.307，P=0.000；蛋白：r=0.368， P=0.000)。单因素分析结果显示：组织学分级、浸润深度、TNM分期、淋巴结转移、GRP78高表达及pERK高表达与胃癌预后有关(P均＜0.05)。浸润全层、低分化、TNM分期晚、有淋巴结转移、GRP78高表达及pERK高表达患者生存时间短。多因素生存分析结果结果显示：GRP78高表达与GRP78低表达相比生存时间差异有统计学意义(P＜0.001)。GRP78高表达的胃癌患者生存时间短，提示GRP78是负性的预后因子。结论：GRP78和pERK在胃癌中高表达，GRP78和pERK在正常细胞向恶性细胞转化的过程中可能扮演了重要角色，检测pERK和GRP78的表达可能有助于对胃腺癌的预防、早期诊断及预后判断，同时为胃癌治疗寻找新的靶点。揹景與目的：在胃癌的髮生、髮展過程中，內質網應激、細胞的脩複及凋亡是重要的病理生理過程，而GRP78與pERK在其中髮揮瞭重要的作用。研究葡萄糖調節蛋白78(glucose-regulated proteins 78，GRP78)和燐痠化細胞外信號調節激酶(pERK)在胃腺癌、慢性萎縮性胃炎及淺錶性胃炎組織中的錶達，研究它們與胃癌髮生、髮展的關繫。方法：RT-PCR法檢測各25例胃腺癌、慢性萎縮性胃炎和淺錶性胃炎新鮮組織中GRP78、pERK基因錶達；免疫組化法分彆檢測各60例胃腺癌、慢性萎縮性胃炎和淺錶性胃炎組織中GRP78、pERK蛋白錶達，併分析其蛋白錶達與臨床病理參數間的相關性。結果：RT-PCR半定量結果顯示，胃癌組織中GRP78及pERK mRNA的相對錶達水平(1.26±0.18、2.35±0.36)均明顯高于慢性萎縮性胃炎組織(0.89±0.25、1.18±0.25)及淺錶性胃炎組織(0.29±0.09、0.68±0.10)，差異有統計學意義(P＜0.01)。免疫組織化學結果顯示，GRP78及pERK蛋白在胃癌組織中的錶達率(78.3%、88.3%)亦均高于慢性萎縮性胃炎(46.6%、43.3%)及淺錶性胃炎組織(6.7%、5.0%)，差異有統計學意義(P＜0.01)。胃癌組織中GRP78及pERK蛋白錶達與胃癌分化程度、分期、淋巴結轉移等有明顯相關性。GRP78及pERK基因及蛋白錶達水平在胃癌中均呈正相關(基因：r=0.307，P=0.000；蛋白：r=0.368， P=0.000)。單因素分析結果顯示：組織學分級、浸潤深度、TNM分期、淋巴結轉移、GRP78高錶達及pERK高錶達與胃癌預後有關(P均＜0.05)。浸潤全層、低分化、TNM分期晚、有淋巴結轉移、GRP78高錶達及pERK高錶達患者生存時間短。多因素生存分析結果結果顯示：GRP78高錶達與GRP78低錶達相比生存時間差異有統計學意義(P＜0.001)。GRP78高錶達的胃癌患者生存時間短，提示GRP78是負性的預後因子。結論：GRP78和pERK在胃癌中高錶達，GRP78和pERK在正常細胞嚮噁性細胞轉化的過程中可能扮縯瞭重要角色，檢測pERK和GRP78的錶達可能有助于對胃腺癌的預防、早期診斷及預後判斷，同時為胃癌治療尋找新的靶點。
배경여목적：재위암적발생、발전과정중，내질망응격、세포적수복급조망시중요적병리생리과정，이GRP78여pERK재기중발휘료중요적작용。연구포도당조절단백78(glucose-regulated proteins 78，GRP78)화린산화세포외신호조절격매(pERK)재위선암、만성위축성위염급천표성위염조직중적표체，연구타문여위암발생、발전적관계。방법：RT-PCR법검측각25례위선암、만성위축성위염화천표성위염신선조직중GRP78、pERK기인표체；면역조화법분별검측각60례위선암、만성위축성위염화천표성위염조직중GRP78、pERK단백표체，병분석기단백표체여림상병리삼수간적상관성。결과：RT-PCR반정량결과현시，위암조직중GRP78급pERK mRNA적상대표체수평(1.26±0.18、2.35±0.36)균명현고우만성위축성위염조직(0.89±0.25、1.18±0.25)급천표성위염조직(0.29±0.09、0.68±0.10)，차이유통계학의의(P＜0.01)。면역조직화학결과현시，GRP78급pERK단백재위암조직중적표체솔(78.3%、88.3%)역균고우만성위축성위염(46.6%、43.3%)급천표성위염조직(6.7%、5.0%)，차이유통계학의의(P＜0.01)。위암조직중GRP78급pERK단백표체여위암분화정도、분기、림파결전이등유명현상관성。GRP78급pERK기인급단백표체수평재위암중균정정상관(기인：r=0.307，P=0.000；단백：r=0.368， P=0.000)。단인소분석결과현시：조직학분급、침윤심도、TNM분기、림파결전이、GRP78고표체급pERK고표체여위암예후유관(P균＜0.05)。침윤전층、저분화、TNM분기만、유림파결전이、GRP78고표체급pERK고표체환자생존시간단。다인소생존분석결과결과현시：GRP78고표체여GRP78저표체상비생존시간차이유통계학의의(P＜0.001)。GRP78고표체적위암환자생존시간단，제시GRP78시부성적예후인자。결론：GRP78화pERK재위암중고표체，GRP78화pERK재정상세포향악성세포전화적과정중가능분연료중요각색，검측pERK화GRP78적표체가능유조우대위선암적예방、조기진단급예후판단，동시위위암치료심조신적파점。
Background and purpose:In the process of gastric cancer development, cytothesis and apoptosis, and endoplasmic reticulum stress (ERS) are very important pathological processes. Glucose regulated protein 78 (GRP78) and phosphorylated form of extracellular signal-regulated protein kinase (pERK) play important roles in it. This study aimed to investigate the expression of GRP78 and pERK in gastric adenocarcinoma, chronic atrophic gastritis and superficial gastritis, and the role of GRP78 and pERK in the development of gastric adenocarcinoma. Methods:Gastric adenocarcinoma, chronic atrophic gastritis and superifcial gastritis tissues in 60 cases respectively were employed in the study. We chose 25 fresh tissue samples from each group, and the level of GRP78 and pERK mRNA in different tissues were detected by RT-PCR assay. The expressions of GRP78 and pERK in different parafifn samples were detected using immunohistochemistry assay. In addition, the relationships between GRP78 and pERK expression and age, gender, differentiation, invasion, disease stage, and lymphoid node metastasis were analyzed. Results: The expression level of GRP78 and pERK mRNA in gastric adenocarcinoma(1.26±0.18, 2.35±0.36) were significantly higher than chronic atrophic gastritis (0.89±0.25, 1.18±0.25) and superficial gastritis (0.29±0.09, 0.68±0.10, P<0.01). The positive ratio of GRP78 expression in gastric adenocarcinoma, chronic atrophic gastritis and superficial gastritis were 78.3%, 46.6%, 6.7%. The positive ratios of pERK expression were 88.3%, 43.3%, 5.0%, respectively. The GRP78 and pERK expression in different tissues were signiifcantly different (P<0.01). GRP78 and pERK expression were positively correlated with differentiation, disease stage and lymph node metastasis. There was a positive correlation between the gene and protein expression of GRP78 and pERK with a Pearson correlation value of 0.307 and 0.368, respectively. Both univariate and multivariate analysis revealed that GRP78 was related to the prognosis of gastric adenocarcinoma. Conclusion:GRP78 and pERK may play an important role in the transition of normal gastric cells to malignant cells. The expression of these two genes enhances tumor progression. Overexpression of GRP78 and pERK is significantly correlated with poor prognosis in patients with gastric adenocarcinoma. The determination of the expression of GRP78 and pERK might be helpful for the prevention, early diagnosis of gastric carcinoma. Particularly, GRP78 is valuable for the judgement of prognosis, and might be a new target for the treatment of gastric adenocarcinoma.