RANK-ligand (RANKL) expression in young breast cancer patients and during pregnancy.
RANK-ligand (RANKL) expression in young breast cancer patients and during pregnancy.
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DOI：
10.1186/s13058-015-0538-7
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发表时间：
2015-02-21
期刊：
影响因子：
--
通讯作者：
Sotiriou C
中科院分区：
文献类型：
--
作者：
Azim HA Jr;Peccatori FA;Brohée S;Branstetter D;Loi S;Viale G;Piccart M;Dougall WC;Pruneri G;Sotiriou C
RANKL在妊娠期乳腺发育中非常重要，并介导了孕甾酮诱导的乳腺癌的发生和进展。尚无关于妊娠对年轻乳腺癌患者RANK/RANKL表达影响的临床数据。我们使用了我们先前发表的65例妊娠和130例匹配的年轻乳腺癌患者的数据集，这些患者具有完整的临床，病理和生存信息。85%的患者也有可用的转录组学数据。使用H评分通过免疫组织化学对原发性肿瘤和邻近正常组织进行RANK/RANKL表达。我们研究了RANK/RANKL在妊娠和非妊娠患者中表达的差异及其与临床病理特征和预后的关系。我们还评估了与原发性肿瘤中RANK/RANKL表达相关的基因和途径。RANKL在妊娠组中的表达高于RANK，无论是在肿瘤还是在癌旁正常组织中，均与其他临床病理因素无关（均P <0.001）。18.7%的妊娠患者和5.3%的非妊娠患者的肿瘤显示≥ 10%的细胞表达3 + RANKL。RANKL在孕激素受体阳性和管腔A样肿瘤中的表达显著增高，与Ki-67呈负相关（均P <0.001）。而RANK在三阴性肿瘤中的表达明显高于阴性肿瘤（P <0.001）。使用假发现率<0.05，151和1，207个基因分别与肿瘤表达的RANKL和RANK表达显著相关。原发性肿瘤中RANKL的高表达与乳腺发育、骨吸收、T细胞增殖和趋化性调节相关的途径相关，而RANK表达与免疫应答和增殖途径相关。在中位随访65个月时，肿瘤内RANK或RANKL表达与妊娠或非妊娠组的无病生存期均无关。妊娠增加RANKL在正常乳腺和原发性肿瘤中的表达。这些结果可以指导RANKL靶向治疗的进一步发展。本文的在线版本（doi：10.1186/s13058 - 015 - 0538 - 7）包含补充材料，可供授权用户使用。
RANKL is important in mammary gland development during pregnancy and mediates the initiation and progression of progesterone-induced breast cancer. No clinical data are available on the effect of pregnancy on RANK/RANKL expression in young breast cancer patients. We used our previously published dataset of 65 pregnant and 130 matched young breast cancer patients with full clinical, pathological, and survival information. 85% of patients had available transcriptomic data as well. RANK/RANKL expression by immunohistochemistry using H-score on the primary tumor and adjacent normal tissue was performed. We examined the difference in expression of RANK/RANKL between pregnant and non-pregnant patients and their association with clinicopathological features and prognosis. We also evaluated genes and pathways associated with RANK/RANKL expression on primary tumors. RANKL but not RANK expression was more prevalent in the pregnant group, both on the tumor and adjacent normal tissue, independent of other clinicopathological factors (both P <0.001). 18.7% of pregnant and 5.3% of non-pregnant patients had tumors showing ≥10% of cells with 3+ RANKL expression. RANKL expression was significantly higher in progesterone receptor-positive, and luminal A-like tumors, with negative correlation with Ki-67 (all P <0.001). On the contrary, RANK expression was higher in triple negative tumors (P <0.001). Using false discovery rate <0.05, 151 and 1,207 genes were significantly correlated with tumor-expressed RANKL and RANK expression by immunohistochemistry, respectively. High RANKL expression within primary tumor was associated with pathways related to mammary gland development, bone resorption, T-cell proliferation and regulation of chemotaxis, while RANK expression was associated with immune response and proliferation pathways. At a median follow-up of 65 months, neither RANK nor RANKL expression within tumor was associated with disease free survival in pregnant or non-pregnant group. Pregnancy increases RANKL expression both in normal breast and primary tumors. These results could guide further development of RANKL-targeted therapy. The online version of this article (doi:10.1186/s13058-015-0538-7) contains supplementary material, which is available to authorized users.
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影响因子：
11.5
作者：
Azim, Hatem A., Jr.;Michiels, Stefan;Loi, Sherene
通讯作者：
Loi, Sherene
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
3.1
作者：
Azim, Hatem A., Jr.;Botteri, Edoardo;Peccatori, Fedro A.
通讯作者：
Peccatori, Fedro A.
影响因子：
64.8
作者：
Asselin-Labat, Marie-Liesse;Vaillant, Francois;Visvader, Jane E.
通讯作者：
Visvader, Jane E.
影响因子：
64.8
作者：
Gonzalez-Suarez, Eva;Jacob, Allison P.;Dougall, William C.
通讯作者：
Dougall, William C.