Low expression of ULK1 is associated with operable breast cancer progression and is an adverse prognostic marker of survival for patients
Low expression of ULK1 is associated with operable breast cancer progression and is an adverse prognostic marker of survival for patients
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DOI：
10.1007/s10549-012-2080-y
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发表时间：
2012-07-01
影响因子：
3.8
通讯作者：
Zhu, Xiao-Feng
中科院分区：
文献类型：
--
作者：
Tang, Jun;Deng, Rong;Zhu, Xiao-Feng
ULK1在自噬中发挥重要作用，广泛参与乳腺癌的发生发展。然而，对ULK1在人乳腺癌中的功能和表达的研究还很少。在这项研究中，我们发现，与匹配的正常组织相比，14个乳腺癌组织中有10个（71.4%）的ULK1 mRNA和蛋白水平下降。此外，对包含298例非转移性浸润性乳腺癌组织和73例匹配的邻近非癌组织的组织芯片进行ULK1免疫组化染色。70.1%的乳腺癌标本显示ULK1无至弱染色，然而，78.1%的邻近非癌标本显示ULK1中度至强染色。统计学分析显示，ULK1表达与肿瘤大小（r = -0.176, P = 0.002）、淋巴结状态（r = -0.115, P = 0.048）、病理分期（r = -0.177, P = 0.002）呈负相关。log-rank检验显示，ULK1水平较低的患者远端无转移生存时间（P = 0.008）和肿瘤相关生存时间（P = 0.008）显著缩短。多因素Cox回归分析发现，ULK1表达被认为是独立的预后因素（P = 0.034）。此外，在我们的乳腺癌队列中，ULK1与LC3A的表达呈显著正相关（r = 0.401, P < 0.001）， ULK1与p62的表达呈显著负相关（r = -0.226, P < 0.001）。这些发现表明，ULK1的表达降低与乳腺癌的进展有关，并与自噬能力下降密切相关。ULK1也可能被用作乳腺癌患者的一种新的预后生物标志物。
ULK1 plays an important role in autophagy which is widely involved in the development of breast cancer. However, the function and expression of ULK1 in human breast cancer is still scarcely explored. In this study, we showed that the mRNA and protein levels of ULK1 decreased in 10 of 14 (71.4 %) breast cancer tissues, compared with matched normal tissues. Furthermore, immunohistochemical staining of ULK1 was performed on the tissue microarray containing 298 non-metastatic invasive breast primary cancer tissues and 73 matched adjacent noncancerous tissues. 70.1 % breast cancer specimens displayed none to weak staining of ULK1, however, 78.1 % adjacent noncancerous specimens showed moderate to strong staining of ULK1. Statistical analysis revealed that ULK1 expression was negatively correlated with tumor size (r = -0.176, P = 0.002), lymph node status (r = -0.115, P = 0.048), and pathological stage (r = -0.177, P = 0.002). The log-rank test showed that patients with lower level of ULK1 had a significant shorter distant metastasis-free survival time (P = 0.008) and cancer-related survival time (P = 0.008). Multivariate Cox regression analysis found that ULK1 expression was recognized as an independent prognostic factor (P = 0.034). In addition, a significant positive correlation between expression of ULK1 and LC3A (r = 0.401, P < 0.001), and a significant negative correlation between expression of ULK1 and p62 (r = -0.226, P < 0.001) were observed in our breast cancer cohort. These findings suggest that decreased expression of ULK1 is associated with breast cancer progression, together with closely related to decreased autophagic capacity. ULK1 also may be used as a novel prognostic biomarker for breast cancer patients.