Cancer stem cell-related factors are associated with the efficacy of pre-operative chemoradiotherapy for locally advanced rectal cancer

Abstract

Abstract. pre-operative chemoradiotherapy (crt) is an important neoadjuvant therapy for locally advanced rectal cancer. in the present study, we investigated the factors that influence the efficacy of pre-operative CRT in locally advanced rectal cancer. We divided 50 patients with locally advanced rectal carcinoma treated with pre-operative crt into two groups according to the grade of tumor response to pre-operative crt: low-sensitivity group and high-sensitivity group. as candidates for the prediction of sensitivity to preoperative crt, clinicopathological factors and 12 biomarkers, including factors related to tumor growth, cell cycle, apoptosis, tumor stroma and cancer stem cells, were examined immunohistochemically in 48 resected specimens. thirty-one tumors showed high sensitivity and 19 showed low sensitivity to pre-operative crt. the status of stem cell-related factors, CD133 and CD24, was significantly associated respectively with sensitivity to pre-operative crt (p=0.003, p=0.029). in 10 tumors positive for both cd133 and cd24, low sensitivity to crt was found in 9 (90%), whereas in 16 tumors negative for both cd133 and cd24, low sensitivity was found in 3 (19%). Other pathological parameters were not associated with tumor response to pre-operative crt. in conclusion, overexpression of cancer stem cell-related factors, cd133 and cd24, is associated with the sensitivity of locally advanced rectal cancer to pre-operative crt.Introduction colorectal cancer is a leading cause of morbidity and mortality in developed countries (1). in Japan, an increasingly Westernized diet has led to a high incidence of colorectal cancer. patients with rectal cancers are known to have an increased rate of local recurrence and decreased survival time compared to patients with tumors of the colon, a result due primarily to the surgical constraints imposed by the location of the rectum within the pelvis (2).pre-operative chemoradiotherapy (crt) is a neoadjuvant therapy for locally advanced rectal cancer that reduces the incidence of local recurrence and improves survival (3). therefore, crt is widely used in many countries of the world. however, several tumors show a marked response to crt, whereas others do not. Furthermore, several adverse events related to crt, such as enteritis, anorexia, cardiac/ thromboembolic events, radiation dermatitis and hematologic toxicity, were reported to occur at frequencies of 6-43% (4). thus, pre-operative indicators of chemoradiosensitivity are required to avoid unnecessary application of pre-operative crt, yet little is known about potential biological markers that may be associated with response to pre-operative crt.recently, the discovery of rare subpopulations of cancer stem cells has created a new focus in cancer research. the heterogeneity of tumors can be explained by the concept of cancer stem cells supported by anti-apoptotic signaling. there are a few reports on cancer stem cells related to chemoradiation resistance (5,6). therefore, in this study we investigated the factors, inclu...

Prediction of response to preoperative chemoradiotherapy in patients with locally advanced rectal cancer

“…Several studies confirmed elevated CD133 expression was associated with resistance to CRT in LARC (57)(58)(59)(60). The status of CD24 was also found to be significantly associated with response to CRT (p = 0.029) (58).…”

Candidate genes and potential mechanisms for chemoradiotherapy sensitivity in locally advanced rectal cancer

“…In CRT-treated patients with colorectal cancer, the upregulation of circulating cancer stem cell markers is vital for clinical parameters including CRT sensitivity (36). Hiroishi et al (37) indicated that prominin-1 and signal transducer CD24 contributed to the sensitivity of preoperative CRT for LARC. In the present study, the GO functional analysis indicated that signaling pathways regulating the pluripotency of stem cells had the highest enrichment of upregulated miRNA-target genes, including PIK3CG and APC2 .…”

Molecular Biology: Are We Getting Any Closer to Providing Clinically Useful Information?

“…44 Similarly, CD133, another CSC marker, has been reported to correlate with decreased sensitivity to CRT. 45 However, in a study by Sprenger et al evaluating pre-and posttreatment samples from 126 rectal cancer patients, the absolute pretreatment CD133 expression was not associated with response, though the authors noted that patients who had an increase in CD133 after therapy had less tumor regression and worse survival. 46 While the use of CSC-based biomarkers in CRC is still in its infancy, there is exciting potential in terms of predicting treatment efficacy, as well as providing novel therapeutic targets.…”