Authors: Toru Takeda Hiroto Izumi Shohei Kitada Hidetaka Uramoto Takashi Tasaki Li Zhi Xin Guo Yuichiro Kawatsu Tomoko Kimura Seichi Horie Atsunori Nabeshima Hirotsugu Noguchi KeYong Wang Yasuyuki Sasaguri Kimitoshi Kohno Sohsuke Yamada
Publish Date: 2014/07/26
Volume: 35, Issue: 10, Pages: 10555-10569
Abstract
Highmobility group box HMGB proteins are ubiquitous abundant nuclear nonhistone 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 paraffinembedded 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 54 871 and 31 500 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 diseasespecific 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
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