AXIN2 genomic profile as a predictive marker of early stage right-sided colorectal cancer tumors with microsatellite instability

PALMA S; GURRUCHAGA A; RAFFA CI; ABBA MC; LACUNZA E

Mar del Plata

Congreso; LXIII Reunión Anual de la Sociedad Agentina de Investigación Clínica; 2018

Sociedad Agentina de Investigación Clínica

Ithas been previously demonstrated that AXIN2 gene behaves as an oncogenepromoting colorectal cancer development by activating the WNT signaling.However, AXIN2 has also been categorized and transcriptomic profile of AXIN2 incolorectal cancer we performed an in silico analysis on data obtained from fourcomprehensive studies: Nature 2012 (n=276); Nature Medicine 2013 (n=390); CellReports 2016 (n=619); and Cancer Cell 2018 (n=1134). Bioinformatic tools and Rpackages from Bioconductor were employed for data integrative analysis andvisualization. Results indicate that the frequency of alteration/mutation ofthe gene is usually not higher than 10% of the patients, and it is associatedwith the alteration of genes related with the WNT pathway. A significantassociation between AXIN2 mutated patients and the Instability Microsatellite(MSI) molecular subtype was determined. Also, there was an association with thetumor location, being AXIN2 more frequently mutated in tumors derived from theright colon. Staging and sample type were evaluated and the group of AXIN2mutated showed an association with earlier stages compared with the othergroup. Overall Survival analysis indicated that patients who carry mutations inthe AXIN2 gene have a worse prognosis (p0.05). However, patients that harborAXIN2 mutation were, in turn, more responsive to chemotherapy treatment (p0.01).Likewise, we determined a negative association between the AXIN2 mutation andthe gene expression, positioning it as a tumor suppressor gene rather than asan oncogene. The association of AXIN2 mutation with poor prognosis and itsappearance in early stages, position it as a prognostic and predictive markerin the defined molecular subtype of right-sided colorectal tumor with MSI. At thisregard, it has been defined that colorectal cancers with MSI are predominantlylocated on the right-sided and had an early pathological stage.