title: Right- and left-sided colorectal cancers display distinct expression profiles and the anatomical stratification allows a high accuracy prediction of lymph node metastasis.
abstract: Accurate preoperative prediction of lymph node metastasis and degree of tumor invasion would facilitate an appropriate decision of the extent of surgical resection of cancers to reduce unnecessary complication or to minimize the risk of recurrence in patients. We analyzed gene expression profiles characteristic of the invasiveness of colorectal carcinoma in a total of 89 cases, using a cDNA array and pattern classification algorithms. We set binary classes for a panel of clinicopathologic parameters, each of which was divided at different levels for categories (discrete) or values (continuous). We searched an optimal combination of genes to discriminate the classes by using of a feature subset selection algorithm, which was applied to a set of genes preselected on the basis of statistical difference in expression (two-sided t test, P < or = 0.05). We used a sequential forward feature selection which additively searched a combination of genes, giving a minimal leave-one-out classification error rate of a k-nearest neighbor classifier. In the process of gene preselection, we found a remarkable difference in the expression pattern of genes according to the anatomical location of cancers. The difference was most prominent when the classes were set for cecum, ascending colon, transverse colon, and descending colon (CATD) versus sigmoid colon and rectum (SR). By stratifying these two locations, we were able to extract gene expression profiles characteristic of the classes of the presence versus absence of lymph node metastasis, lymphatic invasion, vascular invasion and degree of mural invasion, and pathological stages, with an accuracy of more than 90%. These results suggest that colorectal cancers harbor distinct molecular pathophysiological statuses according to their right-to-left locations, of which stratification is important for pattern classification of cDNA array data.
authors.affiliation: Department of Pathology/Pathophysiology, Division of Pathophysiological Science, Hokkaido University, Sapporo, Japan.
authors.forename: Kazuteru
authors.initials: K
authors.lastname: Komuro
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Tada
authors.forename: Eiji
authors.initials: E
authors.lastname: Tamoto
authors.forename: Akiko
authors.initials: A
authors.lastname: Kawakami
authors.forename: Akihiro
authors.initials: A
authors.lastname: Matsunaga
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Teramoto
authors.forename: Gaku
authors.initials: G
authors.lastname: Shindoh
authors.forename: Minoru
authors.initials: M
authors.lastname: Takada
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Murakawa
authors.forename: Motoshi
authors.initials: M
authors.lastname: Kanai
authors.forename: Nozomi
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Norihiro
authors.initials: N
authors.lastname: Nishimura
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Hamada
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ishizu
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ikeda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kondo
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Katoh
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Moriuchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshiki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000503:physiopathology / Q000556:secondary*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods / Q000592:standards; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods / Q000592:standards*; D011237:Predictive Value of Tests; D015203:Reproducibility of Results