MicroRNA in rectal cancer

Abstract

In rectal cancer, one of the most common cancers worldwide, the proper staging of the disease determines the subsequent therapy. For those with locally advanced rectal cancer, a neoadjuvant chemoradiotherapy (CRT) is recommended before any surgery. However, response to CRT ranges from complete response (responders) to complete resistance (non-responders). To date we are not able to separate in advance the first group from the second, due to the absence of a valid biomarker. Therefore all patients receive the same therapy regardless of whether they reap benefits. On the other hand almost all patients receive a surgical resection after the CRT, although a watch-and-wait procedure or an endoscopic resection might be sufficient for those who responded well to the CRT. Being highly conserved regulators of gene expression, microRNAs (miRNAs) seem to be promising candidates for biomarkers. Many studies have been analyzing the miRNAs expressed in rectal cancer tissue to determine a specific miRNA profile for the ailment. Unfortunately, there is only a small overlap of identified miRNAs between different studies, posing the question as to whether different methods or differences in tissue storage may contribute to that fact or if the results simply are not reproducible, due to unknown factors with undetected influences on miRNA expression. Other studies sought to find miRNAs which correlate to clinical parameters (tumor grade, nodal stage, metastasis, survival) and therapy response. Although several miRNAs seem to have an impact on the response to CRT or might predict nodal stage, there is still only little overlap between different studies. We here aimed to summarize the current literature on rectal cancer and miRNA expression with respect to the different relevant clinical parameters.

Keywords: Chemoradiotherapy; Expression; MicroRNA; Polymorphism; Rectal cancer; Response.

Figure 1

Differential expression of microRNAs in rectal cancer. The differentially expressed microRNAs (miRNAs) in rectal cancer compared to normal rectal tissue are listed, sorted by studies, respectively. The correlating circles show the number of differentially expressed miRNAs in the mentioned studies and point out the number of miRNAs overlapping between those studies.

Figure 2

Differential expression of miRNAs dependent on response to preoperative chemoradiotherapy. miRNAs in up arrow callouts are significantly higher expressed; those in down arrow callouts are significantly lower expressed. On the left site there are miRNAs, isolated from pretherapeutic biopsies, which are supposed to predict response or non-response, respectively. The miRNAs in the bottom localized on the right side, are found to be significantly higher or lower expressed in post-therapeutic tumor biopsies of non-responders after chemoradiotherapy compared to pretherapeutic biopsies. ¹Lopes-Ramos et al[69], 2014; ²Hotchi et al[68], 2013; ³Della Vittoria Scarpati et al[66], 2012; ⁴Bhangu et al[70], 2014; ⁵Svoboda et al[64], 2012; ⁶Svoboda et al[63], 2008; ⁷Drebber et al[65], 2011.