HPK1 positive expression associated with longer overall survival in patients with estrogen receptor-positive invasive ductal carcinoma‑not otherwise specified.
HPK1 positive expression associated with longer overall survival in patients with estrogen receptor-positive invasive ductal carcinoma‑not otherwise specified.
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DOI：
10.3892/mmr.2017.7131
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发表时间：
2017-10
影响因子：
3.4
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Wang J;Song L;Yang S;Zhang W;Lu P;Li S;Li H;Wang L
造血祖细胞激酶1（HPK 1）属于丝/苏氨酸激酶中的丝裂原活化蛋白激酶激酶激酶激酶激酶（MAP 4K）家族，与人类多种胃肠道恶性肿瘤的发生和进展相关。然而，HPK 1表达与乳腺癌，特别是浸润性导管癌-未另行说明（IDC-NOS）发展之间的潜在关联尚未得到研究。为了解决这一差距，本研究旨在评估HPK 1在IDC-NOS样本中的表达，并确定与临床预后指标的关系，如雌激素受体（ER），孕激素受体（PR）和人表皮生长因子受体2（HER 2）的表达水平，以及IDC-NOS患者的总生存期。采用免疫组化、Western blotting和逆转录-定量聚合酶链反应（RT-PCR）检测148例IDC-NOS组织中HPK 1 mRNA和蛋白的表达。148例中有54例（36.5%）HPK 1阳性，100例（67.6%）ER阳性。在后者中，28%（28/100）为HPK 1阳性，观察到HPK 1表达与ER阳性显著负相关（P=0.002; r=-0.254）。此外，43.2%（64/148）和32.4%（48/100）的IDC-NOS组织分别为PR或HER 2阳性;然而，这两种指标均与HPK 1无关（分别为P=0.109和P=0.558）。HPK 1表达、腋淋巴结转移和TNM分期是ER阳性组总生存期的独立影响因素（P<0.05），HPK 1阳性与总生存期增加相关（P=0.048）。HPK 1 mRNA在IDC NOS和正常乳腺组织中的表达无显著性差异，而HPK 1蛋白在IDC NOS中的表达明显低于正常乳腺组织（P<0.05）。这些结果表明，HPK 1蛋白可能是一个潜在的有效的IDC-NOS治疗靶点。
Hematopoietic progenitor kinase 1 (HPK1) belongs to the mitogen activated protein kinase kinase kinase kinase (MAP4K) family of serine/threonine kinases, which have been associated with the incidence and progression of a variety of gastrointestinal malignant tumors in humans. However, the potential association between HPK1 expression and breast cancer, particularly invasive ductal carcinoma-not otherwise specified (IDC-NOS) development, has not yet been examined. To address this gap, the present study aimed to evaluate HPK1 expression in IDC-NOS samples and to determine a relationship with clinical prognostic indicators, such as the expression levels of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), as well as overall survival of the patients with IDC-NOS. HPK1 mRNA and protein expression in samples from 148 patients with IDC-NOS were detected using immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction. A total of 54 out of 148 (36.5%) samples were HPK1-positive, and 100 out of 148 (67.6%) were ER-positive. Of the latter, 28% (28/100) were HPK1-positive, and a significant negative association of HPK1 expression with ER positivity was observed (P=0.002; r=−0.254). In addition, 43.2% (64/148) and 32.4% (48/100) of IDC-NOS tissues were PR- or HER2-positive, respectively; however, neither indicator correlated with HPK1 (P=0.109 and P=0.558, respectively). HPK1 expression, axillary lymph node metastasis and tumor-node-metastasis (TNM) stage were identified as independent factors of overall survival (OS) in the ER-positive group (P<0.05), and HPK1 positivity was associated with increased OS (P=0.048). HPK1 mRNA levels did not differ between IDC-NOS and normal adjacent breast tissues, whereas HPK1 protein levels were lower in IDC-NOS (P<0.05). These results suggested that HPK1 protein may be a potentially effective IDC-NOS therapeutic target.
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影响因子：
3.4
作者：
Wang, Yi;Luo, Hongmei;Yang, Luoyan
通讯作者：
Yang, Luoyan
影响因子：
2.7
作者：
Chen-Deutsch X;Kutner A;Harrison JS;Studzinski GP
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Studzinski GP
影响因子：
4.4
作者：
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影响因子：
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作者：
Webber, Colleen;Gospodarowicz, Mary;Groome, Patti A.
通讯作者：
Groome, Patti A.
影响因子：
3.9
作者：
Ogston, KN;Miller, ID;Heys, SD
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Heys, SD