RHBDD2: A CANCER 5FU RESPONSIVE GENE, AS A POTENTIAL PROGNOSTIC AND THERAPEUTIC MARKER IN COLORECTAL CANCER TREATED WITH NEOADJUVANT CHEMOTHERAPY

PALMA SABINA; ZWENGER ARIEL O; GRACIELA GIGOLA; CROCE MV; ABBA MC; LACUNZA E

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA; 2016

Colorectal cancer (CRC) is a molecular heterogeneous disease.Sequencing technologies have characterized this heterogeneityto define molecular subtypes that allo􀁙 stratify patients sothat they receive adequate and specific treatment. 􀀴H􀀤􀀦􀀦􀀔 gene􀁙as found overexpressed in the advanced stages of breast andC􀀴 cancers. 􀀲revious studies also demonstrated that 􀀴H􀀤􀀦􀀦􀀔expression is induced under stress caused by agents such as 􀀦TTor 􀀗Fu as an adaptive response. This led to its association 􀁙ithE􀀴 stress and the 􀀷􀀲􀀴 path􀁙ay. 􀀫n this study 􀀴H􀀤􀀦􀀦􀀔 expression􀁙as evaluated in C􀀴C exposed to chemotherapeutic agents,in order to understand its role in tumor biology and establish itspotential utility as a mar􀁍er of chemoresistance or as a therapeutictarget. 􀀴H􀀤􀀦􀀦􀀔 expression 􀁙as analyzed in paired samples􀀊before and after treatment􀀋 of advanced rectal cancer. 􀀫n most ofthem an abrupt decrease in protein expression after the treatment􀁙as observed. Ho􀁙ever, in those 􀁙here there 􀁙as no reductionin the expression, a significant association 􀁙ith metastasis 􀁙asfound. Similar results 􀁙ere obtained in rat induced C􀀴 tumors.Furthermore, colon cancer cell lines 􀁙ere employed to evaluatethe effect of 􀀗Fu on the expression of 􀀴H􀀤􀀦􀀦􀀔 and the 􀀷􀀲􀀴genes. 􀀴esults confirmed that 􀀗Fu induced the transient expressionof all of them, but 􀁙ith variation according to the molecularsubtype of the cell line. Ta􀁍en together, results allo􀁙 us to inferthat 􀀴H􀀤􀀦􀀦􀀔 is a protein related to the 􀀷􀀲􀀴 that responds tostress caused by neoadjuvant treatment, establishing t􀁙o groupsof post􀀏treatment response􀀜 􀁙ith decreased expression and 􀁙ithoutdecline, being the latter associated 􀁙ith a 􀁙orse prognosis. Thisdifferential response could be associated to the intrinsic tumorsubtype. Establish to 􀁙hich group are the tumors that do not sh o􀁙variation of 􀀴H􀀤􀀦􀀦􀀔 after treatment 􀁙ould give an important valueto the protein as a mar􀁍er for monitoring response to therapy andas a therapeutic target.