Gurzu Simona, Jung Ioan, Sugimura Haruhiko, Stefan-van Staden Raluca Ioana, Yamada Hidetaka, Natsume Hiroko, Iwashita Yuji, Szodorai Rita, Szederjesi Janos
Department of Pathology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology, Targu Mureș 540139, Mureș, Romania.
Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
World J Gastrointest Oncol. 2020 Jul 15;12(7):741-755. doi: 10.4251/wjgo.v12.i7.741.
Although the role of p53 in the evolution and prognosis of gastric cancer (GC) has been extensively examined, the exact mechanism of action is incompletely understood. In the last years, p53-target genes were supposed to be involved in the p53 pathway. One of them is the tumor-suppressor gene Maspin, which codifies the protein with the same name. Maspin activity depends on its subcellular localization. To our knowledge, the possible role of gene in Maspin subcellular localization, in GC cells, has not yet been studied in a large number of human samples.
To evaluate the possible role of wild-type and mutated p53 in Maspin subcellular localization.
The present study included 266 consecutive patients with GC in which gene status, and mutations in exons 2 to 11, respectively, were analyzed and correlated with immunohistochemical expression of p53 and Maspin.
None of the 266 cases showed mutations in exon 9. The rate of mutations was 33.83%. The mutation rate was slightly higher in distally-located GCs, with a lower degree (≤ 5 buds/ high power fields) of dyscohesivity ( < 0.01). The wild-type cases had a longer survival, compared with mutant GCs, especially in patients without lymph node metastases, despite the high depth of tumor infiltration ( = 0.01). The Dukes-MAC-like staging system was proved to have the most significant independent prognostic value ( < 0.01). The statistical correlations proved that gene mutations in exon 7 might induce knockdown of Maspin, but wild-type p53 can partially restore nuclear Maspin expression and decrease the metastatic potential of gastric adenocarcinoma cells.
Downregulated Maspin might be induced by mutations in exon 7 of the gene but wild-type p53 can partially restore nuclear Maspin expression. These findings should be proved in experimental studies.
尽管p53在胃癌（GC）的发生发展及预后中的作用已得到广泛研究，但其确切作用机制仍未完全明确。近年来，p53靶基因被认为参与p53信号通路。其中之一是肿瘤抑制基因Maspin，它编码同名蛋白质。Maspin的活性取决于其亚细胞定位。据我们所知，在大量人类样本中，尚未研究该基因在GC细胞中Maspin亚细胞定位方面的可能作用。
评估野生型和突变型p53在Maspin亚细胞定位中的可能作用。
本研究纳入266例连续的GC患者，分析其基因状态以及外显子2至11的突变情况，并与p53和Maspin的免疫组化表达进行相关性分析。
266例病例中无一例显示外显子9突变。基因的突变率为33.83%。远端GC的突变率略高，黏附性差的程度较低（≤5个芽/高倍视野）（<0.01）。与突变型GC相比，野生型病例的生存期更长，尤其是在无淋巴结转移的患者中，尽管肿瘤浸润深度较深（=0.01）。Dukes-MAC样分期系统被证明具有最显著的独立预后价值（<0.01）。统计相关性证明，外显子7的基因突变可能导致Maspin表达下调，但野生型p53可部分恢复Maspin的核表达并降低胃腺癌细胞的转移潜能。
Maspin表达下调可能由基因外显子7的突变诱导，但野生型p53可部分恢复Maspin的核表达。这些发现应在实验研究中得到证实。
