title: Low expression of ULK1 is associated with operable breast cancer progression and is an adverse prognostic marker of survival for patients.
abstract: 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.
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.forename: Rong
authors.initials: R
authors.lastname: Deng
authors.forename: Rong-Zhen
authors.initials: RZ
authors.lastname: Luo
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Shen
authors.forename: Mu-Yan
authors.initials: MY
authors.lastname: Cai
authors.forename: Zi-Ming
authors.initials: ZM
authors.lastname: Du
authors.forename: Shan
authors.initials: S
authors.lastname: Jiang
authors.forename: Ming-Tian
authors.initials: MT
authors.lastname: Yang
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Fu
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Zhu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D001343:Autophagy; D000071189:Autophagy-Related Protein-1 Homolog; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000071456:Sequestosome-1 Protein; D018709:Statistics, Nonparametric
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D000071189:Autophagy-Related Protein-1 Homolog; D017346:Protein Serine-Threonine Kinases; C484754:ULK1 protein, human