Particular gene upregulation and p53 heterogeneous expression in TP53-mutated maxillary carcinoma.
Particular gene upregulation and p53 heterogeneous expression in TP53-mutated maxillary carcinoma.
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DOI：
10.3892/ol.2017.6751
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发表时间：
2017-10
期刊：
影响因子：
2.9
通讯作者：
Oshima T
中科院分区：
文献类型：
--
作者：
Kudo I;Esumi M;Kusumi Y;Furusaka T;Oshima T
已有研究表明，肿瘤蛋白p53（TP 53）突变的上颌鳞状细胞癌较无TP 53突变的上颌鳞状细胞癌对化疗更敏感。然而，TP53突变与治疗耐药性之间的关系仍不清楚。作为了解TP53突变与非TP53突变肿瘤之间生物学差异的第一步，对TP53突变与非TP53突变的上颌鳞状细胞癌进行了全面的基因表达分析。总共42个基因被鉴定为差异表达>4倍。使用定量聚合酶链反应对其mRNA进行定量，表明在TP 53突变肿瘤中与TP 53野生型肿瘤相比，有18个基因高表达，3个基因低表达。这18个基因包括8个细胞粘附基因（DSC3、GRHL1、EPPK1、PROM2、ANXA 8、DSP、JUP和KRT 6B）和4个细胞生长抑制基因（SFN、CLCA 2、SAMD 9和TP 63）。在这些基因中，表达显著增加的DSC3、SFN和CSTA在TP53突变肿瘤的免疫组织化学染色中也显示出高蛋白表达。TP53突变的肿瘤仅在邻近基质的肿瘤边缘的肿瘤细胞中表现出TP53蛋白的高核染色，而肿瘤内部对TP53呈阴性。然而，TP53野生型肿瘤的所有肿瘤细胞均表现出TP53蛋白的阳性核染色。综合研究结果表明，TP53突变的肿瘤具有与癌症进展和恶性转化相关的表型相反的表型，并且在肿瘤内部和边缘之间表现出肿瘤细胞异质性。
It has been demonstrated that tumor protein p53 (TP53) mutation in maxillary squamous cell carcinoma, is more treatment-resistant compared with the carcinoma without TP53 mutation. However, the association between TP53 mutation and treatment resistance remains unclear. As a first step in understanding the biological differences between tumors with and without TP53 mutation, a comprehensive gene expression analysis of maxillary squamous cell carcinoma with or without TP53 mutation was performed. A total of 42 genes were identified to be differentially expressed by >4-fold. Quantification of their mRNA using quantitative polymerase chain reaction indicated 18 genes with high expression and three genes with low expression in TP53 mutated tumors vs. TP53 wild-type tumors. The 18 genes included eight cell adhesion (DSC3, GRHL1, EPPK1, PROM2, ANXA8, DSP, JUP, and KRT6B) and four cell growth inhibition (SFN, CLCA2, SAMD9 and TP63) genes. Among these genes, DSC3, SFN, and CSTA, whose expression was markedly increased, also demonstrated high protein expression in immunohistochemical staining of TP53 mutated tumors. The TP53 mutated tumors demonstrated high nuclear staining of the TP53 protein only in tumor cells at the tumor margins adjacent to the stroma, whereas the tumor interior was negative for TP53. However, all tumor cells of TP53 wild-type tumors exhibited positive nuclear staining for the TP53 protein. The combined findings suggest that TP53 mutated tumors possess a phenotype opposite to that associated with cancer progression and malignant transformation, and exhibit tumor cell heterogeneity between the tumor interior and margins.
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