RRM1 gene expression evaluated in the liquid biopsy (blood cfRNA) as a non-invasive, predictive factor for radiotherapy-induced oral mucositis and potential prognostic biomarker in head and neck cancer patients

Article type: Research Article

Authors: Mlak, Radosław^{a; *} | Powrózek, Tomasz^a | Brzozowska, Anna^b | Homa-Mlak, Iwona^a | Mazurek, Marcin^a | Małecka-Massalska, Teresa^a

Affiliations: [a] Department of Human Physiology, Medical University of Lublin, Lublin, Poland | [b] Department of Oncology, Medical University of Lublin, Lublin, Poland

Correspondence: [*] Corresponding author: Radosław Mlak, Department of Human Physiology, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin, Poland. Tel.: +48 81 448 60 80; Fax: +48 81 448 60 96; E-mail: [email protected].

Abstract: BACKGROUND: Intensified treatment of head and neck cancers (HNC): by radiotherapy (RTH) commonly combined with cytotoxic drugs is associated with oral mucositis (OM). Changes in the functioning of nucleotide synthesis pathway (RNR1, coded by RRM1 gene) can modulate the efficiency of cellular DNA repair mechanisms and influence the risk of occurrence and severity of OM in HNC patients after RTH. OBJECTIVE: The objective of this study was to evaluate the correlation between expression of RRM1 gene measured in free circulating RNA (cfRNA) and the risk of more severe OM and disease-free survival (DFS) and overall survival (OS) in patients undergoing RTH for HNC. METHODS: The study included 60 patients treated with RTH for HNC. RRM1 gene expression was examined in circulating RNA isolated from peripheral blood plasma (before treatment). RESULTS: High RRM1 gene expression was significantly associated with higher risk of grade 3 OM after 5 (OR = 4.97), 6 (OR = 4.33) and 7 (OR = 3.50) weeks of RTH. Expression of RRM1 gene was not significantly related with risk of DFS and OS shortening (however well separated Kaplan-Meier curves might suggest its potential prognostic impact). CONCLUSIONS: The evaluation of RRM1 gene expression in cfRNA allows for estimation of the risk of severe OM in patients subjected to RTH.

Keywords: cfRNA, DNA repair, head and neck cancer, liquid biopsy, oral mucositis, radiotherapy, RRM1, survival

DOI: 10.3233/CBM-171082

Journal: Cancer Biomarkers, vol. 22, no. 4, pp. 657-667, 2018