Prognostic impact of total and tyrosine phosphorylated GIV/Girdin in breast cancers
Prognostic impact of total and tyrosine phosphorylated GIV/Girdin in breast cancers
复制标题
总磷酸化 GIV/Girdin 和酪氨酸磷酸化对乳腺癌的预后影响
DOI：
10.1096/fj.201600500
复制
发表时间：
2016-11-01
期刊：
影响因子：
4.8
通讯作者：
Ghosh, Pradipta
中科院分区：
文献类型：
--
作者：
Dunkel, Ying;Diao, Kexin;Ghosh, Pradipta
G相互作用囊泡相关蛋白（GIV，又名Girdin）是三聚体G蛋白Gi的鸟嘌呤交换因子（GEF），也是一种真正的转移相关基因，作为通过G蛋白中间体扩增酪氨酸信号的平台。在这里，我们提出了第一个探索性的生物标志物研究进行了一个队列的187例乳腺癌患者，以评估预后的作用，总GIV（tGIV）和酪氨酸磷酸化GIV（pYGIV）在各种分子亚型。Kaplan-Meier无复发生存分析显示，tGIV的存在，无论是细胞质或细胞核，预后差，但细胞核tGIV有更大的预后影响（P = 0.007，在早期和P = 0.0048，在晚期临床阶段）。细胞质中激活的pYGIV在晚期临床阶段具有最大的预后影响（P = 0.006）。此外，我们发现细胞质pYGIV和细胞核tGIV的预后影响是相加的（风险比19.0548; P = 0.0002）。令人惊讶的是，在人表皮生长因子受体2阳性肿瘤中观察到了细胞核tGIV/细胞质pYGIV的这种累加效应（风险比16.918; P = 0.0005），但在三阴性乳腺癌中没有观察到。在三阴性乳腺癌中，tGIV和胞质pYGIV没有预后影响;然而，pYGIV的膜结合预后不良（P = 0.026）。tGIV和pYGIV均与临床分期、肿瘤大小、病理类型、淋巴结转移和BRCA 1/2状态无关。我们的结论是，pYGIV和tGIV的免疫细胞化学检测可以作为一个有效的诊断。基于tGIV/pYGIV在每个分子亚型内的不同预后影响，我们提出了一种诊断算法。对更大队列的进一步研究对于严格评估该算法在乳腺癌患者中预测结果的有效性和稳健性至关重要。Diao，K.，阿斯纳尔，北，斯旺森湖，刘，L.，朱伟，米，X。-是的，Ghosh，P.乳腺癌中总的和酪氨酸磷酸化的GIV/Girdin的预后影响。
G-interacting vesicle-associated protein (GIV, aka Girdin) is a guanine exchange factor (GEF) for the trimeric G protein Gi and a bona fide metastasis-related gene that serves as a platform for amplification of tyrosine-based signals via G-protein intermediates. Here we present the first exploratory biomarker study conducted on a cohort of 187 patients with breast cancer to evaluate the prognostic role of total GIV (tGIV) and tyrosine phosphorylated GIV (pYGIV) across the various molecular subtypes. A Kaplan-Meier analysis of recurrence-free survival showed that the presence of tGIV, either cytoplasmic or nuclear, carried poor prognosis, but that nuclear tGIV had a greater prognostic impact (P = 0.007 in early and P = 0.0048 in late clinical stages). Activated pYGIV in the cytoplasm had the greatest prognostic impact in late clinical stages (P = 0.006). Furthermore, we found that the prognostic impacts of cytoplasmic pYGIV and nuclear tGIV were additive (hazard ratio 19.0548; P = 0.0002). Surprisingly, this additive effect of nuclear tGIV/cytoplasmic pYGIV was observed in human epidermal growth factor receptor 2-positive tumors (hazard ratio 16.918; P = 0.0005) but not in triple-negative breast cancers. In triple-negative breast cancers, tGIV and cytoplasmic pYGIV had no prognostic impact; however, membrane-association of pYGIV carried a poor prognosis (P = 0.026). Both tGIV and pYGIV showed no correlation with clinical stage, tumor size, pathologic type, lymph node involvement, and BRCA1/2 status. We conclude that immunocytochemical detection of pYGIV and tGIV can serve as an effective prognosticator. On the basis of the differential prognostic impact of tGIV/pYGIV within each molecular subtype, we propose a diagnostic algorithm. Further studies on larger cohorts are essential to rigorously assess the effectiveness and robustness of this algorithm in prognosticating outcome among patients with breast cancer.Dunkel, Y., Diao, K., Aznar, N., Swanson, L., Liu, L., Zhu, W., Mi, X.-Y., Ghosh, P. Prognostic impact of total and tyrosine phosphorylated GIV/Girdin in breast cancers.