Prognostic Significance of Tag SNP rs1045411 in HMGB1 of the Aggressive Gastric Cancer in a Chinese Population.
Compelling evidences have suggested that high mobility group box-1 (HMGB1) gene plays a crucial role in cancer development and progression. This study aimed to evaluate the effects of single nucleotide polymorphisms (SNPs) in HMGB1 gene on the survival of gastric cancer (GC) patients. Three tag SNPs from HMGB1 gene were selected and genotyped using Sequenom iPEX genotyping system in a cohort of 1030 GC patients (704 in training set, 326 in validation set). Multivariate Cox proportional hazard model and Kaplan-Meier Curve were used for prognosis analysis. AG/AA genotypes of SNP rs1045411 in HMGB1 gene were significantly associated with better overall survival (OS) in a set of 704 GC patients when compared with GG genotypes (HR = 0.77, 95% CI: 0.60-0.97, P = 0.032). This prognostic effect was verified in an independent validation set and pooled analysis (HR = 0.80, 95% CI: 0.62-0.99, P = 0.046; HR = 0.78, 95% CI: 0.55-0.98, P = 0.043, respectively). In stratified analysis, the protective effect of rs1045411 AG/AA genotypes was more prominent in patients with adverse strata, compared with patients with favorable strata. Furthermore, strong joint predictive effects on OS of GC patients were noted between rs1045411 genotypes and Lauren classification, differentiation, stage or adjuvant chemotherapy. Additionally, functional assay indicated a significant effect of rs1045411 on HMGB1 expression. Our results suggest that rs1045411 in HMGB1 is significantly associated with clinical outcomes of Chinese GC patients after surgery, especially in those with aggressive status, which warrants further validation in other ethnic populations.
Department of General Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710032, China.
Guoqiang
G
Bao
Department of General Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710032, China.
Falin
F
Qu
Department of Ophthalmology, School of Medicine, Emory University, Atlanta, GA 30322, United States of America.
Li
L
He
Department of General Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710032, China.
Huadong
H
Zhao
Department of General Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710032, China.
Nan
N
Wang
Xijing Hospital of Digestive Disease, The Fourth Military Medical University, Xi'an, 710032, China.
Gang
G
Ji
Department of General Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710032, China.
Xianli
X
He
D044466:Asian People; D001483:Base Sequence; D017024:Chemotherapy, Adjuvant / Q000379:methods; D005753:Gastric Mucosa / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D057809:HEK293 Cells; D024243:HMGB1 Protein / Q000235:genetics* / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D013270:Stomach / Q000473:pathology / Q000601:surgery; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000601:surgery
D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C574053:MIRN505 microRNA, human; D035683:MicroRNAs