title: Gene expression profile can predict pathological response to preoperative chemoradiotherapy in rectal cancer.
abstract: BACKGROUND
  Preoperative chemoradiotherapy (CRT) has been widely used to improve local control of disease and to preserve the anal sphincter in the treatment of rectal cancer. However, the response to CRT differs among individual tumors. Our purpose of this study was to identify a set of discriminating genes that can be used for characterization and prediction of response to CRT in rectal cancer.
  
  
  METHODS
  Seventeen rectal cancer patients who underwent preoperative CRT (40 Gy radiotherapy combined with S-1) were studied. Biopsy specimens were obtained from rectal cancer patients before preoperative CRT and were analyzed by focused DNA microarray (132 genes) and immunohistochemistry. Response to CRT was determined by histopathologic examination of surgically resected specimens and patients were classified as responders (grade 2 or 3) or non-responders (grade 0 or 1).
  
  
  RESULTS
  Of the 17 samples, 10 were classified as responders and 7 as non-responders. Seventeen genes were differentially expressed at significant levels (p<0.05) between responders and non-responders. All genes showed higher expression in responders as compared with non-responders. The list of discriminating genes included matrix metalloproteinase- (MMP), apoptosis- (nuclear factor kappa light polypeptide gene enhancer in B-cells 2 (NFKB2), transforming growth factor beta 1 (TGFB1)), DNA repair- (topoisomerase 1 (TOP1)), and cell proliferation (integrin, beta 1 (ITGB1))-related genes. In the immunohistochemistry of MMP7, 4 responders were judged as showing overexpression of MMP7. On the other hand, none of the non-responders were judged as showing overexpression of MMP7.
  
  
  CONCLUSIONS
  Gene expression patterns of diagnostic biopsies can predict pathological response to preoperative CRT with S-1 in rectal cancer.
authors.affiliation: Department of Surgery, Institute of Health Biosciences, The University of Tokushima, Kuramoto, Tokushima, Japan. mnishioka@clin.med.tokushima-u.ac.jp
authors.forename: Masanori
authors.initials: M
authors.lastname: Nishioka
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shimada
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kurita
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwata
authors.forename: Shinya
authors.initials: S
authors.lastname: Morimoto
authors.forename: Kozo
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Jun
authors.initials: J
authors.lastname: Higashijima
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Miyatani
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D016000:Cluster Analysis; D003131:Combined Modality Therapy; D004338:Drug Combinations; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010094:Oxonic Acid / Q000627:therapeutic use; D011237:Predictive Value of Tests; D011300:Preoperative Care / Q000379:methods*; D011379:Prognosis; D011878:Radiotherapy / Q000379:methods; D012004:Rectal Neoplasms / Q000235:genetics* / Q000628:therapy*; D005641:Tegafur / Q000627:therapeutic use
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C108257:ITGB1BP1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7