The prognostic roles of PYCR2 and ZBTB18 expression in tissues of colorectal carcinoma and Non-neoplastic tissues; an immunohstochemical study

Abstract Background: it will be important to detect novel biomarkers which are responsible for progression and spread of CRC for better evaluation of patients’ prognosis, better management and development of recent therapeutic targets. Pyrroline-5-carboxylate reductase 2 (PYCR2), in humans is encoded on chromosome 1q42.12. PYCR2 metabolic activity was linked to oncogenesis in many cancers. ZBTB18, a zinc finger transcriptional repressor was found to have tumor suppressor role and was found to be methylated in CRC.Detailed assessment of prognostic roles of PYCR2 and ZBTB18 CRC patients are not sufficiently studied. Aim of the study was to evaluate tissue protein expression of PYCR2 and ZBTB18 in CRC and adjacent non-neoplastic intestinal tissues to detect their roles in CRC carcinogenesis, progression and metastases. Patients and methods: After application of inclusion criteria, 60 CRC patients were included in the study. Tissue samples from tumor and adjacent non-neoplastic tissues of included patients were stained with PYCR2 and ZBTB18.Patients were followed up for about 30 months (range from 10-36 month). We correlate between markers expression, clinicopathological and prognostic parameters.Results: upregulation of PYCR2 and down regulation of ZBTB18 was found in CRC than adjacent non-neoplastic colonic mucosa (p= 0.026 and p<0.001 respectively). High expression of PYCR2 and low expression of ZBTB18 were positively correlated with large tumor size, higher grade, advanced tumor stage, presence of spread to lymph node and presence of distant metastases (p<0.001). High PYCR2 and low ZBTB18 expression were signifi­cantly associated with poor response to therapy (p = 0.008, 0.0.17 respectively), high incidence of progression and relapse recurrence (p=0.005), unfavorable OS rate (p=0.001).Conclusions: High expression of PYCR2 and low expression of ZBTB18 were independent predictors of CRC, progression, poor prognosis and unfavorable patient OS and PFS rates.