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目的:通过检测组氨酸三聚体核苷结合蛋白1(histidine triad nucleotide-binding protein1,HINT1)mRNA及其蛋白质在肾透明细胞癌(clear cell renal cell carcinoma,ccRCC)中的表达情况,探讨其与临床病理特征的关系。方法:应用实时荧光定量(real-time fluorescence quantitative,RFQ)-PCR和免疫组织化学分别从mRNA和蛋白质水平检测HINT1在36例新鲜ccRCC组织、37例新鲜正常肾组织(其中29例配对)、30例石蜡包埋ccRCC组织与12例石蜡包埋正常肾组织中的表达水平,并分析其与临床病理特征间的关系。结果:HINT1mRNA在29例配对ccRCC和癌旁正常肾组织中的表达量分别为0.209±0.033和0.733±0.136(P<0.001),在36例ccRCC和37例癌旁正常肾组织中的表达量分别为0.245±0.035和0.694±0.108(P<0.001)。HINT1蛋白在癌旁正常肾组织中的阳性表达率为100%(12/12),弥漫性分布于细胞核及细胞质中,其中近曲小管表达强度高于远曲小管。肾小球基膜、肾小囊壁层上皮细胞可见HINT1蛋白部分表达,其强度低于肾小管,肾间质未见阳性表达。HINT1蛋白在ccRCC中的阳性表达率为60%(18/30),同样分布于细胞核及细胞质,癌组织间质阴性(P<0.01)。HINT1在mRNA和蛋白质水平表达趋势一致,在ccRCC中表达水平低于癌旁正常肾组织,并且在T3-4晚期肿瘤中表达量低于T1-2早期肿瘤中的表达量(P<0.05);但2者在不同Fuhrman核分级、性别、年龄和肿瘤大小中的表达差异无统计学意义(P>0.05)。结论:HINT1可能在ccRCC发病机制中发挥肿瘤抑制作用,其表达异常可能与翻译水平之前的异常调控有关。推测HINT1mRNA和蛋白质的异常表达可作为ccRCC发生和进展的预后指标。
Objective: To investigate the expression of histidine triad nucleotide-binding protein 1 (HINT1) mRNA and its protein in clear cell renal cell carcinoma (ccRCC) And clinicopathological features. Methods: The expression of HINT1 was detected in 36 cases of fresh ccRCC tissues, 37 cases of fresh normal kidney tissues (including 29 cases of paired cases), 30 of them were detected by real-time fluorescence quantitative (RFQ) -PCR and immunohistochemistry Cases of paraffin-embedded ccRCC tissues and 12 cases of paraffin-embedded normal renal tissue expression levels, and analyze the relationship between clinicopathological features. Results: The expression levels of HINT1 mRNA in 29 paired ccRCC and adjacent normal renal tissues were 0.209 ± 0.033 and 0.733 ± 0.136, respectively (P <0.001). The expression levels of HINT1 mRNA in 36 cases of ccRCC and 37 cases of adjacent normal renal tissues were 0.245 ± 0.035 and 0.694 ± 0.108 (P <0.001). The positive expression rate of HINT1 protein in adjacent normal renal tissues was 100% (12/12), diffusely distributed in the nucleus and cytoplasm. The expression intensity of proximal tubule was higher than distal tubule. Glomerular basement membrane, epithelial cells of the renal capsule showed that the expression of HINT1 protein was partially lower than that of renal tubules, renal interstitium and no positive expression. The positive expression rate of HINT1 protein in ccRCC was 60% (18/30), which was also distributed in the nucleus and cytoplasm. The interstitial cancerous tissue was negative (P <0.01). The expression level of HINT1 in mRNA and protein was the same, the expression level in ccRCC was lower than that in adjacent normal renal tissues, and the expression level of HINT1 in T3-4 advanced tumors was lower than that in early T1-2 tumors (P <0.05). However, there was no significant difference in the expression of Fuhrman’s nuclear grade, sex, age and tumor size (P> 0.05). Conclusion: HINT1 may play a tumor suppressor role in the pathogenesis of ccRCC. The abnormal expression of HINT1 may be related to the abnormal regulation before translation. It is speculated that abnormal expression of HINT1 mRNA and protein may be used as a prognostic indicator of the occurrence and progression of ccRCC.