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目的胃肠道间质瘤(GIST)涵盖着多种的临床过程和转归,而多数的GIST可通过单纯外科手术治愈,但术后复发率可达20～40%。目前普遍认为,胃肠道间质瘤起源于Cajal间质细胞(ICC)的功能获得性突变。然而,GIST恶性进展的遗传基础却知之甚少。方法对32例胃和小肠GIST切除组织作寡核苷酸微阵列分析,共检测了54,613个探针的表达水平。再应用实时逆转录聚合酶链式反应和免疫组化方法对代表性的基因芷片数据进行验证。结果 32例胃肠道间质瘤按无偏倚的分层聚类法,依据肿瘤部位连续分为两大类。两大类进一步分成亚类,各亚类根据与各种病理预后指标、转移发生率(P<0.05)和临床转归的相关程度作划分。免疫组化法分析了152例单独的胃GIST病例,显示表达二肽基肽酶Ⅳ(T细胞活化抗原CD26)蛋白的患者,总体生存率和无病生存率均显著下降(P<0.00001)。结论 CD26似乎是恶性胃GIST的一个可靠的生物标志。CD26阴性的病例,术后复发率低至2.0%(2例/102例)。因此,对于此类患者,术后随访可适当放宽。CD26可能在胃GIST的恶性进程中发挥重要作用,并可能成为治疗的靶点。
OBJECTIVE: Gastrointestinal stromal tumors (GISTs) cover a wide range of clinical processes and outcomes. Most GISTs can be cured by simple surgeries, but postoperative recurrence rates can reach 20-40%. It is now generally accepted that gastrointestinal stromal tumors originate from gain-of-function mutations in Cajal interstitial cells (ICC). However, the genetic basis of the malignant progression of GIST is poorly understood. Methods 32 cases of gastric and small intestine GIST resected tissues were analyzed by oligonucleotide microarray. A total of 54,613 probes were detected. Real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry were used to validate the representative gene Zhizhi data. Results According to the unbiased hierarchical clustering method, 32 cases of gastrointestinal stromal tumors were divided into two categories according to the tumor site. The two categories were further divided into subclasses. Each subclass was divided according to various pathological prognostic indicators, incidence of metastasis (P <0.05) and clinical outcome. Immunohistochemical analysis of 152 cases of gastric GIST alone showed that the expression of dipeptidyl peptidase IV (T cell activation antigen CD26) protein in patients with overall survival and disease-free survival were significantly decreased (P <0.00001). Conclusion CD26 appears to be a reliable biomarker of malignant gastric GIST. CD26-negative cases, postoperative recurrence rate as low as 2.0% (2 cases / 102 cases). Therefore, for such patients, postoperative follow-up may be appropriate to relax. CD26 may play an important role in the malignant progression of gastric GIST and may be the target of therapy.