title: Clinical influence of cancer stem cells on residual disease after preoperative chemoradiotherapy for rectal cancer.
abstract: We evaluated the clinical influence of cancer stem cells (CSCs) on residual disease after preoperative chemoradiotherapy (CRT) in patients with rectal cancer. The surgical specimens of 145 patients with residual rectal cancer after preoperative CRT were assessed. To identify CSCs, immunohistochemistry was performed using their surrogate makers (CD44 and aldehyde dehydrogenase 1 [ALDH1]) in full section tissues. Of the 145 cases, ALDH1 and CD44 positivity was found in 80.0 % (n = 116) and 47.6 % (n = 69), respectively; ALDH1 positivity showed weakly positive correlation with CD44 (r s  = 0.269, P = 0.002). ALDH1 and CD44 positivity was related to lower tumor regression grade (TRG) (P = 0.009 and 0.003, respectively). Additionally, ALDH1 positivity was associated with positive circumferential resection margin (P = 0.019). However, ALDH1 and CD44 positivity showed no relationship with KRAS or BRAF mutation. In univariate analysis, ALDH1 positivity was associated with short recurrence-free survival (RFS) (P = 0.005) and rectal cancer-specific survival (RCSS) (P = 0.043), but not CD44 positivity (RFS, P = 0.725; RCSS, P = 0.280). In multivariate analysis, ALDH1 positivity was an independent prognostic factor for poor RFS (P = 0.039; hazard ratio = 2.997; 95 % confidence interval = 1.059-8.478), but not RCSS (P = 0.571). The expression of ALDH1 assessment independently predicts RFS in patients with residual disease after CRT. These results suggest that targeting CSCs could be an effective therapeutic approach to rectal cancer patients receiving preoperative CRT.
authors.affiliation: Department of Pathology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, 807 Hogukno, Buk-gu, Daegu, 41404, Republic of Korea.
authors.forename: Ghilsuk
authors.initials: G
authors.lastname: Yoon
authors.affiliation: Department of Pathology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, 807 Hogukno, Buk-gu, Daegu, 41404, Republic of Korea.
authors.forename: Sol-Min
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Colorectal Cancer Center, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, 807 Hogukno, Buk-gu, Daegu, 41404, Republic of Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, 807 Hogukno, Buk-gu, Daegu, 41404, Republic of Korea. san_0729@naver.com.|Department of Pathology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, 130 Dongdeok-ro, Jung-gu, Daegu, 41944, Republic of Korea. san_0729@naver.com.
authors.forename: An Na
authors.initials: AN
authors.lastname: Seo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000080924:Aldehyde Dehydrogenase 1 Family; D059248:Chemoradiotherapy; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018365:Neoplasm, Residual / Q000235:genetics / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D057234:Preoperative Period; D011379:Prognosis; D016016:Proportional Hazards Models; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012004:Rectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D050697:Retinal Dehydrogenase / Q000378:metabolism
chemical_list: D018960:Hyaluronan Receptors; D007527:Isoenzymes; C117307:KRAS protein, human; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Aldehyde dehydrogenase 1; CD44; Preoperative chemoradiotherapy; Rectal cancer