Kisspeptin and GPR54 immunoreactivity in a cohort of 518 patients defines favourable prognosis and clear cell subtype in ovarian carcinoma.
Kisspeptin and GPR54 immunoreactivity in a cohort of 518 patients defines favourable prognosis and clear cell subtype in ovarian carcinoma.
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DOI：
10.1186/1741-7015-5-33
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发表时间：
2007-11-15
期刊：
影响因子：
9.3
通讯作者：
Aparicio SA
中科院分区：
文献类型：
--
作者：
Prentice LM;Klausen C;Kalloger S;Köbel M;McKinney S;Santos JL;Kenney C;Mehl E;Gilks CB;Leung P;Swenerton K;Huntsman DG;Aparicio SA
Kisspeptins及其G蛋白偶联受体GPR 54是GnRH释放所需的，并与模型系统中的抗转移肿瘤细胞行为相关。后者可能表明它们的过度表达与癌症的更好预后相关。然而，kisspeptin/GPR 54相互作用（自分泌，旁分泌和/或内分泌）也可能以负面方式影响肿瘤行为。在这里，我们第一次将kisspeptin/GPR 54配体-受体对的免疫反应性与一个大的卵巢癌队列的良好预后联系起来。在由518例早期卵巢癌组成的组织微阵列（TMA）上进行kisspeptin和GPR 54的免疫组织化学分析，所有这些都具有相关的临床结果数据。使用0（阴性）、+1（轻度-中度）和+2（强）染色强度量表对TMA进行评分。强染色病例被认为是kisspeptin或GPR 54阳性并指定为1，而所有其他病例被认为是阴性并指定为0。所有统计分析均采用双侧检验进行，p值等于或小于0.05视为显著。Kisspeptin和GPR 54免疫反应性病例在单变量疾病特异性生存期（p = 0.0023，p = 0.0092）以及总生存期（p = 0.0006，p = 0.0002）中显示出有利的预后。此外，kisspeptin是通过多变量疾病特异性（p = 0.0046）和总生存分析（p = 0.0170）确定的有利预后的独立标志物，而GPR 54仅是总生存的独立标志物（p = 0.0303）。Kisspeptin阳性和GPR 54阳性病例均与卵巢癌透明细胞亚型密切相关（p < 0.0001，p < 0.0001），并且GPR 54与透明细胞亚型中总生存率的良好预后显著相关（p = 0.0102）。Kisspeptin和GPR 54免疫反应性与疾病特异性和总生存期的良好预后显著相关，并且与卵巢透明细胞癌亚型显著相关，从而创建了第一个特异于卵巢透明细胞癌的独立预后生物标志物。
Kisspeptins and their G-protein coupled receptor, GPR54 are required for GnRH release and have been associated with anti-metastatic tumour cell behaviour in model systems. The latter might suggest that their overexpression would be associated with a better prognosis in cancer. However, kisspeptin/GPR54 interactions (autocrine, paracrine, and/or endocrine) could also impact tumour behaviour in a negative manner. Here, for the first time, we associate the immunoreactivity of the kisspeptin/GPR54 ligand-receptor pair with favourable prognosis in a large cohort of ovarian carcinomas. Immunohistochemical analysis for kisspeptin and GPR54 was performed on a tissue microarray (TMA) consisting of 518 early stage ovarian carcinomas, all with linked clinical outcome data. The TMA was scored using a staining intensity scale of 0 (negative), +1 (mild-moderate), and +2 (strong). Strong staining cases were considered either kisspeptin or GPR54 positive and designated as 1, while all other cases were considered negative and designated 0. All statistical analysis was conducted using two-sided tests and a p value equal to or less than 0.05 was considered significant. Kisspeptin and GPR54 immunoreactive cases show a favourable prognosis in univariable disease specific survival (p = 0.0023, p = 0.0092), as well as in overall survival (p = 0.0006, p = 0.0002). Furthermore, kisspeptin is an independent marker for favourable prognosis as determined by multivariable disease specific (p = 0.0046) and overall survival analysis (p = 0.0170), while GPR54 is an independent marker for overall survival only (p = 0.0303). Both kisspeptin positive and GPR54 positive cases are strongly associated with the ovarian carcinoma clear cell subtype (p < 0.0001, p < 0.0001), and GPR54 is significantly associated with favourable prognosis in overall survival within the clear cell subtype (p = 0.0102). Kisspeptin and GPR54 immunoreactivity are significantly associated with favourable prognosis in both disease specific and overall survival, as well as being significantly associated with the clear cell ovarian carcinoma subtype, thereby creating the first independent prognostic biomarkers specific for ovarian clear cell carcinomas.
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影响因子：
4.1
作者：
Castellano, J. M.;Navarro, V. M.;Tena-Sempere, M.
通讯作者：
Tena-Sempere, M.
DOI：
10.1073/pnas.1834399100
发表时间：
2003-09-16
影响因子：
11.1
作者：
de Roux, N;Genin, E;Milgrom, E
通讯作者：
Milgrom, E
DOI：
10.1006/bbrc.2001.5470
发表时间：
2001-09-07
影响因子：
3.1
作者：
Hori, A;Honda, S;Fujino, M
通讯作者：
Fujino, M
影响因子：
4
作者：
Jiang, Y;Berk, M;Xu, Y
通讯作者：
Xu, Y
影响因子：
10.3
作者：
Lee, JH;Miele, ME;Welch, DR
通讯作者：
Welch, DR