title: Gene expression of colorectal cancer: preoperative genetic diagnosis using endoscopic biopsies.
abstract: In colorectal cancer, to predict the response to chemo- and/or radio-therapy or the existence of lymph node metastasis preoperatively, a more competent diagnostic system is required, in addition to conventional diagnosis based on morphology and pathology. The application of gene expression profiling to preoperative cancer diagnosis using endoscopic biopsies could enable the selection of a more appropriate therapy for patients. In this study, we evaluated the feasibility of gene expression profiling using preoperative biopsies of colorectal tumors in a clinical setting, by investigating the influence of intra-tumor heterogeneity on the profiles and testing the prediction ability of tumor malignancy. Under endoscopic examination, two biopsies were sampled from each of 10 colorectal cancers and 10 adenomas, and their gene expression data were obtained using cDNA microarrays. The intra- and inter-tumor heterogeneities of the profiles were compared with unsupervised clustering analysis. Molecular prediction of tumor malignancy using biopsies was performed with the supervised classification algorithm. In clustering analysis, almost all paired biopsies from the same tumors joined each other. Pearson's correlation coefficients of the profiles between biopsies from the same tumors (mean, 0.83) were significantly greater than those of the profiles between biopsies from other cancers (mean, 0.58) (p<0.0001). In the supervised classification method, malignancy was correctly predicted in 39 out of 40 biopsies with 8-71 informative genes. Gene expression profiling using endoscopic biopsies of colorectal tumors revealed that the intra-tumor heterogeneity was smaller than the inter-tumor heterogeneity and tumor malignancy was correctly predicted. Our findings suggest that the technique of gene expression profiling accurately represents the biological properties of colorectal cancer and could help the preoperative diagnosis of this disease.
authors.affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, Japan.
authors.forename: Takamichi
authors.initials: T
authors.lastname: Komori
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takemasa
authors.forename: Makoto
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Masaaki
authors.initials: M
authors.lastname: Motoori
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kato
authors.forename: Nobuteru
authors.initials: N
authors.lastname: Kikkawa
authors.forename: Naomasa
authors.initials: N
authors.lastname: Kawaguchi
authors.forename: Masataka
authors.initials: M
authors.lastname: Ikeda
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Sekimoto
authors.forename: Kenichi
authors.initials: K
authors.lastname: Matsubara
authors.forename: Nariaki
authors.initials: N
authors.lastname: Matsuura
authors.forename: Morito
authors.initials: M
authors.lastname: Monden
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D000465:Algorithms; D001706:Biopsy / Q000379:methods*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D003933:Diagnosis; D004724:Endoscopy / Q000379:methods*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012334:RNA, Neoplasm / Q000378:metabolism
chemical_list: D012334:RNA, Neoplasm