Open AccessCombined analysis of KRAS mutation and p16INK4a and p14ARF methylation status in locally advanced rectal carcinoma treated with preoperative chemoradiotherapy
Author(s) -
Bojana Kožik,
Milena Krajnović,
Nikola Kokanov,
Snežana Jovanović-Ćupić,
Ana Božović,
Ljubomir Todorović,
Vesna Mandusic
Publication year - 2022
Publication title -
archives of biological sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.217
H-Index - 25
eISSN - 1821-4339
pISSN - 0354-4664
DOI - 10.2298/abs220222011k
Subject(s) - kras , p14arf , medicine , methylation , oncology , colorectal cancer , chemoradiotherapy , dna methylation , carcinoma , cancer research , cancer , gene , tumor suppressor gene , biology , carcinogenesis , genetics , gene expression
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.