SWATH-MS Analysis of FFPE Tissues Identifies Stathmin as a Potential Marker of Endometrial Cancer in Patients Exposed to Tamoxifen.,Journal of Proteome Research

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SWATH-MS Analysis of FFPE Tissues Identifies Stathmin as a Potential Marker of Endometrial Cancer in Patients Exposed to Tamoxifen.
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2020-04-28 , DOI: 10.1021/acs.jproteome.0c00064
Lucia Janacova ₁ , Jakub Faktor ₂ , Lenka Capkova ₁ , Vendula Paralova ₁ , Anna Pospisilova ₁ , Jan Podhorec _{2,

3} , Holger Alexander Ebhardt _{4,

5} , Roman Hrstka ₂ , Rudolf Nenutil ₂ , Ruedi Aebersold _{4,

6} , Pavel Bouchal ₁

Affiliation

A specific form of endometrial cancer (EC) can develop in breast cancer patients previously treated with tamoxifen (ET), an antagonist of estrogen receptor (ER) that inhibits proliferation of ER positive breast cancer. ET tumors have a different phenotype than endometrial tumors, which typically develop de novo without previous exposure to tamoxifen (EN). Here we aimed to identify specific protein markers that could serve as specific molecular targets in either phenotype. A set of total 45 formalin-fixed paraffin-embedded (FFPE) endometrial tumor tissues and adjacent myometrium tissue samples were analyzed using LC–MS/MS in SWATH-MS mode. We found that calcyphosin (CAPS) levels were elevated in EN tumors compared to ET tumors. The higher CAPS level in EC tissue invading to myometrium supports its relationship to EC aggressiveness. Further, stathmin (STMN1) levels were found significantly elevated in ET versus EN tumors and significantly associated with patient survival. This finding connects elevated levels of this cell cycle regulating, proliferation-associated protein with tamoxifen exposure. In summary, using SWATH-MS we show that CAPS and STMN1 should be recognized as clinicopathologically different EC markers of which STMN1 is specifically connected with a previous tamoxifen exposition.

中文翻译：

FFPE组织的SWATH-MS分析确定Stathmin是接触他莫昔芬的患者子宫内膜癌的潜在标志物。

子宫内膜癌（EC）的特定形式可能在先前接受他莫昔芬（ET）治疗的乳腺癌患者中发展，他莫昔芬（ET）是雌激素受体（ER）的拮抗剂，可抑制ER阳性乳腺癌的增殖。ET肿瘤与子宫内膜肿瘤的表型不同，子宫内膜肿瘤通常从头发展之前未接触过他莫昔芬（EN）。在这里，我们旨在鉴定可以在任一表型中用作特定分子靶标的特定蛋白质标记。使用SWATH-MS模式下的LC-MS / MS分析了一组总共45个福尔马林固定石蜡包埋（FFPE）子宫内膜肿瘤组织和相邻子宫肌层组织样品。我们发现，与ET肿瘤相比，EN肿瘤中的钙磷蛋白（CAPS）水平升高。侵入子宫肌层的EC组织中较高的CAPS水平支持了它与EC侵袭性的关系。此外，发现ET和EN肿瘤中的stathmin（STMN1）水平显着升高，并且与患者生存率显着相关。这一发现将这种细胞周期调节的，与增殖相关的蛋白质的水平升高与他莫昔芬的暴露联系起来。综上所述，

更新日期：2020-07-02

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