Leucine‑rich repeat‑containing G protein‑coupled receptor 5 and CD133 expression is associated with tumor progression and resistance to preoperative chemoradiotherapy in low rectal cancer

Abstract

Preoperative chemoradiotherapy has been performed as a standard therapy for advanced low rectal cancer. Cancer stem cells (CSCs) have been reported to contribute to resistance to treatment and patient prognosis. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) and cluster of differentiation (CD133) are putative markers for CSCs. However, their prognostic ability remains unknown, and evaluation of a single marker can be insufficient due to the heterogeneity of cancer. LGR5 and CD133 expression was immunohistochemically evaluated in surgical specimens of 56 patients who received curative resection following chemoradiotherapy for advanced low rectal cancer. In addition, the correlations between their expression levels, and clinicopathological features and patient prognosis were asessed. LGR5 expression was significantly correlated with lymphatic invasion, lymph node metastasis, and tumor node metastasic (TNM) stage. CD133 expression was significantly correlated with vascular invasion and the tumor regression grade. Combined expression was significantly correlated with lymphatic invasion, tumor regression grade and TNM stage, but not with overall, and disease-free survival. LGR5 and CD133 expressions may represent useful markers associated with tumor progression and resistance to chemoradiotherapy in patients with low rectal cancer. Furthermore, combined expression of these markers may be a more useful marker compared with the expression of each single marker.

Immunohistochemical Expression of CD133 and LGR5 in Ulcerative Colitis-associated Colorectal Cancer and Dysplasia

“…CD133 positivity was defined as >5% positively stained cancer cells, consistent with results from our previous study of CD133 expression in colorectal polyps and cancer (11,17). Moreover, LGR5 positivity was defined as >50% positively stained cancer cells, in accordance with our previous study of LGR5 expression in rectal cancer tissue after chemoradiotherapy (18). The sections were independently analyzed in vivo 33: 1279-1284 (2019) 1280 In some glands, intraglandular cellular debris was also CD133-positive ( Figure 1).…”

Molecular Subtypes Are Frequently Discordant Between Lesions in Patients With Synchronous Colorectal Cancer: Molecular Analysis of 59 Patients

“…Immunohistochemistry. All the samples for immunohistochemical analysis were obtained from paraffin-embedded (FFPE) specimens and stained as previously reported (23). The primary antibodies used were as follows: β-catenin (dilution 1:500; BD Transduction Laboratory, San Diego, CA, USA), TP53 (dilution 1:100; Dako, Glostrup, Denmark), MLH1 (dilution 1:50; Dako), PMS2 (dilution 1:50; Dako), MSH2 (dilution 1:50; EMD Millipore, Darmstadt, Germany), and MSH6 (dilution 1:50; BD Transduction Laboratory).…”

Transcriptomic Analyses of Pretreatment Tumor Biopsy Samples, Response to Neoadjuvant Chemoradiotherapy, and Survival in Patients With Advanced Rectal Cancer

“…Various biomarkers are associated with response to CRT in rectal cancer, including the expression of p53, Ki67, thymidylate synthase, and CD133, as well as alterations in KRAS . Furthermore, several studies have reported gene expression signatures using microarray that predict responses to CRT in rectal cancer .…”