title: ULK1: a promising biomarker in predicting poor prognosis and therapeutic response in human nasopharygeal carcinoma.
abstract: Plenty of studies have established that dysregulation of autophagy plays an essential role in cancer progression. The autophagy-related proteins have been reported to be closely associated with human cancer patients' prognosis. We explored the expression dynamics and prognostic value of autophagy-related protein ULK1 by immunochemistry (IHC) method in two independent cohorts of nasopharygeal carcinoma (NPC) cases. The X-tile program was applied to determine the optimal cut-off value in the training cohort. This derived cutoff value was then subjected to analysis the association of ULK1 expression with patients' clinical characteristics and survival outcome in the validation cohort and overall cases. High ULK1 expression was closely associated with aggressive clinical feature of NPC patients. Furthermore, high expression of ULK1 was observed more frequently in therapeutic resistant group than that in therapeutic effective group. Our univariate and multivariate analysis also showed that higher ULK1 expression predicted inferior disease-specific survival (DSS) (P<0.05). Consequently, a new clinicopathologic prognostic model with 3 poor prognostic factors (ie, ULK1 expression, overall clinical stage and therapeutic response) could significantly stratify risk (low, intermediate and high) for DSS in NPC patients (P<0.001). These findings provide evidence that, the examination of ULK1 expression by IHC method, could serve as an effective additional tool for predicting therapeutic response and patients' survival outcome in NPC patients.
authors.affiliation: The State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, PR China; Department of Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangzhou, PR China.
authors.forename: Miao
authors.initials: M
authors.lastname: Yun
authors.affiliation: The State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Bai
authors.affiliation: The State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, PR China; Department of Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangzhou, PR China.
authors.forename: Jia-Xing
authors.initials: JX
authors.lastname: Zhang
authors.affiliation: Department of extracorporeal circulation, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangzhou, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Rong
authors.affiliation: Department of Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangzhou, PR China.
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Weng
authors.affiliation: Department of Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangzhou, PR China.
authors.forename: Zhou-San
authors.initials: ZS
authors.lastname: Zheng
authors.affiliation: Department of Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangzhou, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Radiotherapy, the First Affiliated Hospital, Anhui Medical University, Hefei, PR China.
authors.forename: Zhu-Ting
authors.initials: ZT
authors.lastname: Tong
authors.affiliation: The State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Xiao-Xia
authors.initials: XX
authors.lastname: Huang
authors.affiliation: The State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Yi-Ji
authors.initials: YJ
authors.lastname: Liao
authors.affiliation: The State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Shi-Juan
authors.initials: SJ
authors.lastname: Mai
authors.affiliation: Department of Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangzhou, PR China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Ye
authors.affiliation: The State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D000071189:Autophagy-Related Protein-1 Homolog; D015415:Biomarkers; D002277:Carcinoma / Q000378:metabolism* / Q000401:mortality* / Q000628:therapy; D003131:Combined Modality Therapy; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000628:therapy; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D047908:Intracellular Signaling Peptides and Proteins; D000071189:Autophagy-Related Protein-1 Homolog; D017346:Protein Serine-Threonine Kinases; C484754:ULK1 protein, human