Research Article

Tumor Biology

, Volume 35, Issue 10, pp 10555-10569

First online:

The combination of a nuclear HMGB1-positive and HMGB2-negative expression is potentially associated with a shortened survival in patients with pancreatic ductal adenocarcinoma

  • Toru TakedaAffiliated withDepartment of Health Policy and Management, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health
  • , Hiroto IzumiAffiliated withDepartment of Occupational Pneumology, School of Medicine, University of Occupational and Environmental Health
  • , Shohei KitadaAffiliated withDepartment of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental HealthDepartment of Urology, School of Medicine, University of Occupational and Environmental Health
  • , Hidetaka UramotoAffiliated withDepartment of Second Surgery, School of Medicine, University of Occupational and Environmental Health
  • , Takashi TasakiAffiliated withDepartment of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health
  • , Li ZhiAffiliated withDepartment of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental HealthDepartment of Medical Oncology, The First Hospital of China Medical University
  • , Xin GuoAffiliated withDepartment of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health
  • , Yuichiro KawatsuAffiliated withDepartment of Health Policy and Management, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health
  • , Tomoko KimuraAffiliated withDepartment of Health Policy and Management, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health
    • , Seichi HorieAffiliated withDepartment of Health Policy and Management, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health
    • , Atsunori NabeshimaAffiliated withDepartment of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health
    • , Hirotsugu NoguchiAffiliated withDepartment of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health
    • , Ke-Yong WangAffiliated withDepartment of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental HealthDepartment of Bio-information Research Center, School of Medicine, University of Occupational and Environmental Health
    • , Yasuyuki SasaguriAffiliated withDepartment of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental HealthLaboratory of Pathology, Fukuoka Wajiro Hospital
    • , Kimitoshi KohnoAffiliated withThe President Laboratory, School of Medicine, University of Occupational and Environmental Health
    • , Sohsuke YamadaAffiliated withDepartment of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health Email author 

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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.

Keywords

Pancreatic ductal adenocarcinoma (PDAC) HMGB1 HMGB2 Lymphatic permeation (LI) Prognosis