Laminin C1 expression by uterine carcinoma cells is associated with tumor progression.
Laminin C1 expression by uterine carcinoma cells is associated with tumor progression.
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DOI：
10.1016/j.ygyno.2015.08.025
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发表时间：
2015-11
影响因子：
4.7
通讯作者：
Shih IeM
中科院分区：
文献类型：
--
作者：
Kashima H;Wu RC;Wang Y;Sinno AK;Miyamoto T;Shiozawa T;Wang TL;Fader AN;Shih IeM
与子宫癌肿瘤进展相关的分子标志物定义不明确。在这项研究中，我们确定LAMC 1（一种编码细胞外基质蛋白层粘连蛋白γ1的基因）的上调是否与各种子宫癌亚型和肿瘤进展阶段相关。对正常子宫内膜、子宫内膜不典型增生及150例子宫内膜癌（包括低级别、高级别子宫内膜样癌、浆液性和透明细胞癌）中层粘连蛋白γ1（laminin γ1，LN γ 1）的免疫组化染色进行了分析。进行临床病理相关性以确定生物学意义。癌症基因组图谱（TCGA）数据集用于验证我们的结果。与正常增生期和分泌期子宫内膜层粘连蛋白γ1免疫反应几乎检测不到相比，从不典型增生到低级别子宫内膜样癌再到高级别子宫内膜样癌上皮细胞层粘连蛋白C1染色强度分别增加。Laminin γ1表达与FIGO分期、肌层浸润、宫颈/附件受累、血管淋巴管浸润和淋巴结转移密切相关。同样，对来自TCGA的子宫内膜癌数据集的分析显示，LAMC 1转录水平在高级别子宫内膜样癌中高于低级别子宫内膜样癌。在高级别类胶质瘤细胞系中通过siRNA沉默IAMC 1表达并不影响其增殖活性，但在体外显著抑制细胞运动和侵袭。这些数据表明，层粘连蛋白γ1可能有助于子宫癌的发展和进展，可能通过增强肿瘤细胞的运动和侵袭。层粘连蛋白γ1作为子宫癌的生物标志物和治疗靶点值得进一步研究
Molecular markers associated with tumor progression in uterine carcinoma are poorly defined. In this study, we determine whether upregulation of LAMC1, a gene encoding extracellular matrix protein, laminin γ1, is associated with various uterine carcinoma subtypes and stages of tumor progression. An analysis of the immunostaining patterns of laminin γ1 in normal endometrium, atypical hyperplasia, and a total of 150 uterine carcinomas, including low-grade and high-grade endometrioid carcinomas, uterine serous and clear cell carcinoma, was performed. Clinicopathological correlation was performed to determine biological significance. The Cancer Genome Atlas (TCGA) data set was used to validate our results. As compared to normal proliferative and secretory endometrium, for which laminin γ1 immunore-activity was almost undetectable, increasing laminin C1 staining intensity was observed in epithelial cells from atypical hyperplasia to low-grade endometrioid to high-grade endometrioid carcinoma, respectively. Laminin γ1 expression was significantly associated with FIGO stage, myometrial invasion, cervical/adnexal involvement, angiolymphatic invasion and lymph node metastasis. Similarly, analysis of the endometrial carcinoma data set from TCGA revealed that LAMC1 transcript levels were higher in high-grade than those in low-grade endometrioid carcinoma. Silencing IAMC1 expression by siRNAs in a high-grade endometrioid carcinoma cell line did not affect its proliferative activity but significantly suppressed cell motility and invasion in vitro. These data suggest that laminin γ1 may contribute to the development and progression of uterine carcinoma, likely through enhancing tumor cell motility and invasion. Laminin γ1 warrants further investigation regarding its role as a biomarker and therapeutic target in uterine carcinoma