Abstract
Objective:The study aimed to delineate the gene expression profile of LGR5, HES1 and ATOH1 in young Egyptian rectal cancer (RC) patients and investigate the correlation between expression profiles and clinical outcome. Methods:The study was conducted on 30 young Egyptian RC patients. Expression study of LGR5, HES1 and ATOH1 were performed by quantitative PCR (QPCR) based on comparative Cq method after normalization to adjacent non tumor tissues and ACTB as a reference gene. Patients were followed up for assessment of response to neoadjuvant chemoradiotherapy (CRT) based on revised RECIST1.1. Result:The study detected overexpression of LGR5 and HES1 and down-regulation of ATOH1 in human RC tissues compared to non- tumor tissues. High expression of LGR5 was correlated with more depth of tumor invasion, lymph node (LN) metastasis, advanced cTNM stage and mesorectal fascia (MRF) involvement. More prominently, high LGR5 expression level was associated with poor response to CRT. LGR5 was suggested as unfavorable prognostic biomarker for RC. Conversely, HES1 and ATOH1 expression did not show significant association with most of the studied clinical criteria nor response to CRT. Still, HES1 and ATOH1 were significantly and inversely associated with presence of mucinous component. Conclusion:High LGR5 expression is indicative of poor prognosis among young Egyptian RC patients and is proposed as a predictive marker of resistance to neoadjuvant CRT. However, HES1 and ATOH1 expressions were not prognostic nor predictive of response to CRT. Overall, LGR5, HES1 and ATOH1 gene expression patterns among young onset RC patients, are in line with patterns encountered in older age groups.
Highlights
In Egypt, Colorectal cancer (CRC) is the sixth most common cause of cancer-related deaths, with a relative frequency of 4.2 % (Ibrahim et al.,2014)
The present study was carried out on 30 young Egyptian patients with RC adenocarcinoma who were eligible for neoadjuvant therapy
Expression of LGR5 was significantly higher in patients with regional lymph node (LN) metastasis compared to patients without LN metastasis (p
Summary
In Egypt, Colorectal cancer (CRC) is the sixth most common cause of cancer-related deaths, with a relative frequency of 4.2 % (Ibrahim et al.,2014). The percentage of young-onset CRC cases in Egyptians is strikingly high with more than one third of cases occurring under 40 years (Soliman et al, 1997; Soliman et al, 1999). More than half of the Egyptian population is younger than 50 years, a mounting public health problem of CRC among young adults in Egypt should be highly considered (Silla et al, 2014). A growing number of research proposed cancer stem cells (CSCs), as the main element contributing to tumor progression, relapse, metastasis and therapeutic resistance (Visvader et al, 2008). A thorough understanding of the specific biomarkers and the signaling pathways governing the functions of CSCs is crucial for identification of valuable prognostic markers and therapeutic targets for CRC (Chen et al, 2013)
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