Histone profiling reveals the H1.3 histone variant as a prognostic biomarker for pancreatic ductal adenocarcinoma

BMC Cancer

Research Article

Theresa Kristl¹  György Marko-Varga¹  Agata Sasor²  Bodil Andersson³  Daniel Ansari³  Roland Andersson³  Monika Bauden³ 

[1] Clinical Protein Science & Imaging, Department of Biomedical Engineering, Lund University, Biomedical Center, Lund, Sweden;Department of Pathology, Skåne University Hospital, Lund, Sweden;Department of Surgery, Clinical Sciences Lund, Lund University, Skåne University Hospital, SE-221 85, Lund, Sweden;

关键词: Biomarkers;    Epigenetics;    Histone variants;    H1.3;    LC-MS/MS;    Immunohistochemistry;    Pancreatic Ductal Adenocarcinoma;   

DOI  :  10.1186/s12885-017-3834-z

 received in 2017-04-21, accepted in 2017-11-23,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundEpigenetic alterations have been recognized as important contributors to the pathogenesis of PDAC. However, the role of histone variants in pancreatic tumor progression is still not completely understood. The aim of this study was to explore the expression and prognostic significance of histone protein variants in PDAC patients.MethodsLiquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for qualitative analysis of histone variants and histone related post-translational modifications (PTMs) in PDAC and normal pancreatic tissues. Survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards regression.ResultsHistone variant H1.3 was found to be differentially expressed (p = 0.005) and was selected as a PDAC specific histone variant candidate. The prognostic role of H1.3 was evaluated in an external cohort of patients with resected PDAC using immunohistochemistry. Intratumor expression of H1.3 was found to be an important risk factor for overall survival in PDAC, with an adjusted HR value of 2.6 (95% CI 1.1–6.1), p = 0.029.ConclusionWe suggest that the intratumor histone H1.3 expression as reported herein, may serve as a new epigenetic biomarker for PDAC.

【 授权许可】

CC BY   
© The Author(s). 2017