Low Rap1-interacting factor 1 and sirtuin 6 expression predict poor outcome in radiotherapy-treated Hodgkin lymphoma patients

Abstract

Sirtuins (SIRTs) are a family of histone deacetylases, which widely regulate cellular metabolism and are also involved in DNA repair. Rap1-interacting factor 1 (Rif1) and O⁶-alkylguanine DNA alkyltransferase (MGMT) are DNA-repair enzymes, which may potentially be involved in resistance to treatment of classical Hodgkin lymphoma (HL). We assessed the expression levels of (previously unstudied) SIRT1, SIRT4, SIRT6, Rif1, and MGMT immunohistochemically in 85 patients with untreated classical HL. Aberrant distributions of SIRT1, SIRT4, and SIRT6 were detected in Hodgkin neoplastic Reed–Sternberg (RS) cells compared with reactive elements. Low-level expression of both Rif1 and SIRT6 predicted dismal relapse-free survival in radiotherapy-treated patients (multivariate analysis; HR 8.521; 95% CI 1.714–42.358; p = .0088). Expression levels of SIRT1, 4, and 6 were abnormally distributed in RS cells, suggesting a putative role of aberrant acetylation in classical HL carcinogenesis. Rif1 and SIRT6 may also have substantial prognostic and even predictive roles in classical HL.

Keywords:

• DNA repair
• lymphoma
• radioresistance
• sirtuin
• Rif1

Acknowledgements

This study was supported by the Finnish Anti-Tuberculosis Association under Grant [2016], Väisänen Fund in Terttu-Foundation under Grant (622014), and the Cancer Foundation Finland under Grant [160122/2016]. We thank Mrs Riitta Vuento for her technical assistance in immunohistochemical staining.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2017.1344840.

Additional information

Funding

Finnish Anti-Tuberculosis Foundation10.13039/501100008368

Väisänen Fund622014

Cancer Foundation Finland160122/2016

This study was supported by the Finnish Anti-Tuberculosis Association under Grant [2016], Väisänen Fund in Terttu-Foundation under Grant (622014), and the Cancer Foundation Finland under Grant [160122/2016].