A Novel Predictive Marker of Resistance to Neoadjuvant Chemoradiation Therapy in Young Rectal Cancer Patients

Abstract

The aim of the study was to delineate the gene expression profile of LGR5 in rectal cancer (RC) tissues among young Egyptian patients. The study aimed at investigating the possible link between this cancer stem cells (CSCs) related gene and clinical outcome, including response to neoadjuvant chemo-radiotherapy (CRT). The study was conducted on 30 young Egyptian RC patients, who were recommended to undergo neoadjuvant CRT. Paired tumor and non-tumor adjacent mucosal tissues were obtained from patients by routine biopsy techniques. Total RNA was extracted followed by reverse transcription, then quantitative PCR was performed using SYBR green. Expression levels of several CSCs related gene including LGR5 in tumor relative to adjacent non-tumor tissues were calculated using the comparative Cq method after normalization for the expression of ACTB. Patients were followed up for assessment of response to neoadjuvant CRT based on revised RECIST 1.1. Among CSCs genes that are tested, only Overexpression of LGR5 in human RC tissues compared to non- tumor tissues was detected. Furthermore, correlation analysis showed that higher expression of LGR5 was correlated with more depth of tumor invasion, LN metastasis, advanced cTNM stage and mesorectal fascia involvement. On the other hand, it was not correlated with gender, age, tumor site nor pathological features. These results suggest that LGR5 may not only play an important role in the progression of RC but also serve as a potential unfavorable prognostic biomarker for RC. In addition, high LGR5 expression level was associated with poor response to CRT.ROC curve analysis showed that LGR5 expression is an excellent predictor for response to neoadjuvant therapy. 1- High LGR5 expression is, most likely, indicative of poor prognosis among young Egyptian RC patients. 2- LGR5 expression level is proposed to be a novel predictive marker of resistance to neoadjuvant CRT in young Egyptian RC patients.