Combined analysis of KRAS mutation and p16INK4a and p14ARF methylation status in locally advanced rectal carcinoma treated with preoperative chemoradiotherapy

Kožik Bojana R.; Krajnović Milena M.; Kokanov Nikola S.; Jovanović-Ćupić Snežana P.; Božović Ana M.; Todorović Lidija B.; Mandušić Vesna Lj.

doi:10.2298/ABS220222011K

Archives of Biological Sciences (Jan 2022)

Combined analysis of KRAS mutation and p16INK4a and p14ARF methylation status in locally advanced rectal carcinoma treated with preoperative chemoradiotherapy

Kožik Bojana R.,
Krajnović Milena M.,
Kokanov Nikola S.,
Jovanović-Ćupić Snežana P.,
Božović Ana M.,
Todorović Lidija B.,
Mandušić Vesna Lj.

Affiliations

Kožik Bojana R.: ORCiD; Vinča Institute of Nuclear Sciences, National Institute of the Republic of Serbia, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia
Krajnović Milena M.: ORCiD; Vinča Institute of Nuclear Sciences, National Institute of the Republic of Serbia, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia
Kokanov Nikola S.: ORCiD; Vinča Institute of Nuclear Sciences, National Institute of the Republic of Serbia, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia
Jovanović-Ćupić Snežana P.: ORCiD; Vinča Institute of Nuclear Sciences, National Institute of the Republic of Serbia, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia
Božović Ana M.: ORCiD; Vinča Institute of Nuclear Sciences, National Institute of the Republic of Serbia, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia
Todorović Lidija B.: ORCiD; Vinča Institute of Nuclear Sciences, National Institute of the Republic of Serbia, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia
Mandušić Vesna Lj.: ORCiD; Vinča Institute of Nuclear Sciences, National Institute of the Republic of Serbia, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia

DOI: https://doi.org/10.2298/ABS220222011K
Journal volume & issue: Vol. 74, no. 2
pp. 127 – 134

Abstract

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Current management of locally advanced rectal carcinoma (LARC) involves preoperative chemoradiotherapy (preCRT) before surgery. Despite improved local control rate, the response to preCRT of individual patients is variable and may reflect heterogeneous biological properties among tumors of the same clinical stage. Identifying novel molecular parameters with predictive and/or prognostic value is of great clinical importance for a personalized therapeutic approach. In this study, KRAS mutation status was analyzed by direct sequencing, while methylation-specific polymerase chain reaction (MSP) was used to examine p16INK4a and p14ARF gene methylation status in pretreatment tumor biopsies of 60 patients with LARC. The examined molecular changes of KRAS, p16INK4a and p14ARF genes were mutually independent (p16INK4a/KRAS, P=0.272; p14ARF/KRAS, P=0.923; p16INK4a/p14ARF, P=0.715). However, the simultaneous presence of p14ARF methylation and KRAS mutation was associated with a more frequent appearance of local recurrences and distant metastasis (P=0.027). Moreover, patients with the simultaneous presence of p16INK4a and p14ARF methylation and KRAS mutation had significantly shorter overall survival (P=0.011). The obtained results strongly suggest that combined analyses of examined genetic and epigenetic molecular alterations could contribute to the identification of LARC patient subgroups with more aggressive tumor behavior and worse disease outcome.

Published in Archives of Biological Sciences

ISSN: 0354-4664 (Print); 1821-4339 (Online)
Publisher: University of Belgrade, University of Novi Sad
Country of publisher: Serbia
LCC subjects: Science: Biology (General)
Website: http://www.serbiosoc.org.rs/arch/index.php

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