title: The combination of a nuclear HMGB1-positive and HMGB2-negative expression is potentially associated with a shortened survival in patients with pancreatic ductal adenocarcinoma.
abstract: High-mobility group box (HMGB) proteins are ubiquitous, abundant nuclear non-histone chromosomal proteins that play a critical role in binding to distorted DNA structures and subsequently regulating DNA transcription, replication, repair, and recombination. Both HMGB1 and HMGB2 exhibit a high expression in several human cancers and are closely associated with tumor progression and a poor prognosis. However, the expression patterns of these molecules in pancreatic ductal adenocarcinoma (PDAC) remain to be elucidated. As most cases of postoperative relapse of PDAC occur within the first 2 years, the clinical significance of accurate biomarkers is needed. Therefore, we investigated the correlation between the immunohistochemical HMGB1 and HMGB2 expression and the clinicopathological characteristics and prognosis using 62 paraffin-embedded tumor samples obtained from patients with surgically resected PDAC. The HMGB1/2 expression was considered to be positive when 10 % or more of the cancer cells showed positive nuclear, not merely cytoplasmic, staining. Consequently, the expression of HMGB1/2 was observed in 54 (87.1 %) and 31 (50.0 %) patients, respectively. Unexpectedly, a positive HMGB1 expression was found to have a significantly close relationship with a negative HMGB2 expression. The univariate and multivariate analyses demonstrated that the patients with a HMGB1+ and HMGB2- status had markedly lower disease-specific survival rates, especially within the first 2 years postoperatively, whereas those with a HMGB1+ status alone did not. Therefore, the combination of a HMGB1+ and HMGB2- expression potentially predicts a poor prognosis in patients with PDAC, and these new biomarkers may be useful parameters for clinical management in the early postoperative phase.
authors: Department of Health Policy and Management, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors: Toru
authors: T
authors: Takeda
authors: Hiroto
authors: H
authors: Izumi
authors: Shohei
authors: S
authors: Kitada
authors: Hidetaka
authors: H
authors: Uramoto
authors: Takashi
authors: T
authors: Tasaki
authors: Li
authors: L
authors: Zhi
authors: Xin
authors: X
authors: Guo
authors: Yuichiro
authors: Y
authors: Kawatsu
authors: Tomoko
authors: T
authors: Kimura
authors: Seichi
authors: S
authors: Horie
authors: Atsunori
authors: A
authors: Nabeshima
authors: Hirotsugu
authors: H
authors: Noguchi
authors: Ke-Yong
authors: KY
authors: Wang
authors: Yasuyuki
authors: Y
authors: Sasaguri
authors: Kimitoshi
authors: K
authors: Kohno
authors: Sohsuke
authors: S
authors: Yamada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D005455:Fluorescent Antibody Technique; D024243:HMGB1 Protein / Q000032:analysis / Q000096:biosynthesis*; D024261:HMGB2 Protein / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D034741:RNA, Small Interfering; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D024261:HMGB2 Protein; D034741:RNA, Small Interfering