HIF-1?在高原地区胃癌及胃黏膜癌前病变组织中的表达及临床意义

Clinical signifi cance of HIF-1? expression in gastric malignant transformation in people from high altitude area of Qinghai

目的探讨缺氧诱导因子-1a(hypoxia inducible factor-1a,HIF-1a)在高原地区胃癌及癌前病变患者中的表达与胃黏膜恶变过程中的临床联系及预后评价.方法利用RT-PCR检测7株胃癌细胞系及其27对胃癌和配癌旁正常组织中HIF-1a的表达;进一步利用组织微阵列和免疫组织化学染色检测37例萎缩性胃炎,34例胃黏膜肠化组织,146例胃癌和57例癌旁正常组织中HIF-1a的表达情况.结果RT-PCR检测显示,HIF-1a在7株胃癌细胞系存在差异表达.同时在胃癌组织的表达水平66.6%(18/27)高于癌旁正常组织14.8%(4/27)(P<0.001).免疫组织化学显示,HIF-1a在癌旁正常组织中表达阳性率为26.3%(15/57);萎缩性胃炎组织为64.8%(24/37);肠化生组织为61.7%(21/34);胃癌组织为56.8%(83/146).并且HIF-1a的表达与年龄相关(P<0.05),而与性别、胃癌的分化程度、胃癌患者临床分期等无关.Kaplan-Meier法和COX多因素回归分析提示HIF-1a高表达是术后胃癌患者独立的危险因素(P<0.001),RR=3.229(95%CI:2.024-5.151).结论HIF-1a表达在胃黏膜恶变过程中表达增加,并且与高原地区胃癌患者不良预后的密切相关.

AIM To detect the expression of hypoxia indurible factor-1α（HIF-1α） in gastric malignant transformation in people from high altitude area of Qinghai,China.METHODS RT-PCR was used to detect the expression of HIF-1α gene in 7 cell lines and 27 pairs of GC and matched tumor adjacent normal gastric mucosa tissues.Using tissue microarray including 57 normal gastric mucosa tissues,37 chronic atrophic gastritis tissues,34 intestinal metaplasia tissues,and 146 gastric cancer（GC）tissues,immunohistochemistry（IHC） was performed to detect the level of HIF-1α protein expression.RESULTS The expression of HIF-1α at the mRNA level was different in GC cell lines.HIF-1αexpression in AGS,SGC7901,and N87 cells was higher than that in MGC803,BGC823,PAMC82 and MKN45 cells.The level of HIF-1α expression was significantly higher in GC tissues（66.6%,18/27） compared with normal gastric mucosa tissues（26.3%,15/57;P〈0.001）.IHC data showed that the positive rate of HIF-1α was 64.8%（24/37） in chronic atrophic gastritis tissues,61.7%（21/34） in intestinal metaplasia tissues,and 56.8%（83/146） in GC tissues,all of which were significantly higher than that in normal tissues（26.3%,15/57）.Expression of HIF-1α was positively associated with age in GC（P〈0.05）.Kaplan-Meier analysis showed that patients with a low level of HIF-1α had apparently better survival than those with a high level（P〈0.0001）.HIF-1αprotein（RR=3.229,95%CI：2.024-5.151） was identified to be an independent risk factor for the outcome of GC patients.CONCLUSION High HIF-1α expression is associated with gastric malignant transformation and poor prognosis in high altitude areas.