LRIG1 as a potential novel marker for neoplastic transformation in ocular surface squamous neoplasia.
LRIG1 as a potential novel marker for neoplastic transformation in ocular surface squamous neoplasia.
复制标题
DOI：
10.1371/journal.pone.0093164
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kinoshita S
中科院分区：
文献类型：
--
作者：
Nagata M;Nakamura T;Sotozono C;Inatomi T;Yokoi N;Kinoshita S
富亮氨酸重复序列和免疫球蛋白样蛋白1 （LRIG1）是一种新发现的表皮生长因子受体（EGFR）负调控因子，被认为是一种肿瘤抑制因子。它在人类癌症中并不普遍下调，它在肿瘤转化和肿瘤发生中的作用也没有很好的文献记载。在这项研究中，我们发现LRIG1的表达是眼表鳞状瘤变（OSSN）中肿瘤转化的一个新的潜在标记物。本研究分为两组：1)良性组（3例，乳头状瘤1例，发育不良2例）和2)恶性组（鳞状细胞癌3例）。在两组中，首先对角蛋白4、12、13和15进行免疫荧光分析以表征分化状态，并对Ki67进行免疫荧光分析以评估增殖活性。随后分析LRIG1和EGFR的表达。除1例严重SCC病例外，两组均表达非角化上皮细胞标记物角蛋白4和/或13。角蛋白15，一种未分化的基底细胞标志物，在恶性病例中比在良性病例中表达更强烈。恶性组Ki67指数（33.2%）明显高于良性组（10.9%），差异有统计学意义（P<0.002）。LRIG1的表达仅限于正常角膜上皮组织的基底上皮细胞。有趣的是，在所有良性病例中，LRIG1在整个上皮中表达。而在恶性肿瘤中表达受限或完全消失。相反，EGFR染色在良性病例中表达微弱，而在恶性病例中表达强烈。具有增殖潜能的恶性组织EGFR过表达，LRIG1呈负向下调，这与LRIG1通过抵消EGFR的肿瘤生长特性抑制肿瘤转化一致。我们的研究结果表明，LRIG1的下调可能是OSSN病例中转化和肿瘤发生的一个新的潜在标志物。
The leucine rich repeats and immunoglobulin-like protein 1 (LRIG1) is a newly discovered negative regulator of epidermal growth factor receptor (EGFR) and a proposed tumor suppressor. It is not universally downregulated in human cancers, and its role in neoplastic transformation and tumorigenesis is not well-documented. In this study, we show the expression of LRIG1 as a novel potential marker for neoplastic transformation in ocular-surface squamous neoplasia (OSSN). The following two groups were included in this study: 1) benign group (3 cases; 1 with papilloma and 2 with dysplasia) and 2) malignant group (3 cases with squamous cell carcinoma (SCC)). In both groups, immunofluorescence analysis was firstly performed for keratins 4, 12, 13, and 15 to characterize the state of differentiation, and for Ki67 to evaluate the proliferation activity. Subsequently, LRIG1 and EGFR expression was analyzed. Either keratin 4 and/or 13, both non-keratinized epithelial cell markers, were generally expressed in both groups, except for 1 severe SCC case. Keratin 15, an undifferentiated basal cell marker, was more strongly expressed in the malignant cases than in the benign cases. The Ki67 index was significantly higher (P<0.002) in the malignant group (33.2%) than in the benign group (10.9%). LRIG1 expression was limited to basal epithelial cells in normal corneal epithelial tissue. Interestingly, LRIG1 was expressed throughout the epithelium in all the benign cases. In contrast, its expression was limited or totally disappeared in the malignant cases. Inversely, EGFR staining was faintly expressed in the benign cases, yet strongly expressed in the malignant cases. Malignant tissue with proliferative potential presented EGFR overexpression and inverse downregulation of LRIG1, consistent with LRIG1 being a suppressor of neoplastic transformation by counteracting the tumor growth property of EGFR. Our findings indicate that downregulation of LRIG1 is possibly a novel potential marker of transformation and tumorigenesis in OSSN cases.
登录
查看更多内容
影响因子：
11.2
作者：
Miller, Jamie K.;Shattuck, David L.;Ingalla, Ellen Q.;Yen, Lily;Borowsky, Alexander D.;Young, Lawrence J. T.;Cardiff, Robert D.;Carraway, Kermit L., III;Sweeney, Colleen
通讯作者：
Sweeney, Colleen
影响因子：
168.9
作者：
Newton, R;Ferlay, J;Parkin, DM
通讯作者：
Parkin, DM
影响因子：
11.4
作者：
Gur, G;Rubin, C;Yarden, Y
通讯作者：
Yarden, Y
影响因子：
8
作者：
Goldoni, S.;Iozzo, R. A.;Iozzo, R. V.
通讯作者：
Iozzo, R. V.
LRIG1 在调节恶性胶质瘤侵袭性中的作用
影响因子：
5.2
作者：
Mao, Feng;Wang, Baofeng;Chen, Xiaoping
通讯作者：
Chen, Xiaoping