Serum high mobility group box-1 (HMGB1) is closely associated with the clinical and pathologic features of gastric cancer.
BACKGROUND
High mobility group box-1 (HMGB1) is a newly recognized factor regulating cancer cell tumorigenesis, expansion and invasion. We investigated the correlation between the serum HMGB1 levels and the clinical and pathologic features of gastric cancer and evaluated the validity of HMGB1 as a potential biomarker for the early diagnosis of gastric cancer.


METHODS
A total of 227 subjects were classified into 5 disease groups according to the 'gastritis-dysplasia-carcinoma' sequence of gastric carcinogenesis and their serum levels of HMGB1 were analyzed by an enzyme-linked immunosorbent assay (ELISA) method. Clinical parameters, International Union Against Cancer (UICC) TNM stage, cancer size, differentiation or lymphatic invasion, vascular or perineural invasion and prognosis were used as analysis variables.


RESULTS
The serum HMGB1 levels were significantly different among disease groups (ANOVA, p < 0.05) and HMGB1 levels tended to increase according to the progression of gastric carcinogenesis. Serum HMGB1 levels were significantly associated with depth of invasion, lymph node metastasis, tumor size, and poor prognosis (p < 0.05). However, HMGB1 levels were not associated with patient gender or age, differentiation of tumor cells, or lymphatic, vascular and perineural invasion, or the existence of distant metastasis in advanced cancer (p > 0.05). The sensitivity and specificity of serum HMGB1 was 71% and 67% (cut-off value of 5 ng/ml) for the diagnosis of early gastric cancer, and 70% and 64% (cut-off value of 4 ng/ml) for the diagnosis of high-risk lesions, respectively. These values were greater than those for carcinoembryonic antigen (CEA) (30-40% of sensitivity).


CONCLUSIONS
HMGB1 appears to be a useful serological biomarker for early diagnosis as well as evaluating the tumorigenesis, stage, and prognosis of gastric cancer.
Chung
Hye Won
HW
Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea. hwchungmd@yumc.yonsei.ac.kr
Lee
Sang-Guk
SG
Kim
Heejung
H
Hong
Duck Jin
DJ
Chung
Jae Bock
JB
Stroncek
David
D
Lim
Jong-Baeck
JB
D002272:Carcinoembryonic Antigen / Q000097:blood; D005260:Female; D024243:HMGB1 Protein / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D012372:ROC Curve; D012680:Sensitivity and Specificity; D013274:Stomach Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000473:pathology*; D016019:Survival Analysis
D002272:Carcinoembryonic Antigen; D024243:HMGB1 Protein