title: A four-miRNA signature identified from genome-wide serum miRNA profiling predicts survival in patients with nasopharyngeal carcinoma.
abstract: Recent findings have reported that human serum microRNAs (miRNAs) can be used as prognostic biomarkers in various cancers. We aimed to explore the prognostic value of serum miRNAs in nasopharyngeal carcinoma (NPC) patients. The level of serum miRNA was retrospectively analyzed in 512 NPC patients recruited between January 2001 and December 2006. In the discovery stage, a microarray followed by reverse transcription-quantitative polymerase chain reaction was used to identify differentially altered miRNAs in eight patients with shorter survival and eight patients with longer survival who were well matched by age, sex and clinical stage. The identified serum miRNAs were then validated in all 512 samples, which were randomly divided into a training set and a validation set. Four serum miRNAs (miR-22, miR-572, miR-638 and miR-1234) were found to be differentially altered and were used to construct a miRNA signature. Risk scores were calculated to classify the patients into high- or low-risk groups. Patients with high-risk scores had poorer overall survival [hazard ratio (HR), 2.54; 95% confidence interval (CI), 1.57-4.12; p < 0.001] and distant metastasis-free survival (HR, 3.28; 95% CI, 1.82-5.94; p < 0.001) than those with low-risk scores in the training set; these results were confirmed in the validation and combined sets. The miRNA signature and TNM stage were independent prognostic factors. The combination of the miRNA signature and TNM stage had a better prognostic value than the TNM stage or miRNA signature alone. The four-serum miRNA signature may add prognostic value to the TNM staging system and provide information for personalized therapy in NPC.
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.forename: Rui-Xue
authors.initials: RX
authors.lastname: Cui
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Mao
authors.forename: Ling-Long
authors.initials: LL
authors.lastname: Tang
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.forename: Yi-Kan
authors.initials: YK
authors.lastname: Cheng
authors.forename: Qing-Mei
authors.initials: QM
authors.lastname: He
authors.forename: William C S
authors.initials: WC
authors.lastname: Cho
authors.forename: Li-Zhi
authors.initials: LZ
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D002277:Carcinoma; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D046228:Microarray Analysis; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: biomarkers; microRNA; nasopharyngeal carcinoma; prognosis; serum