title: Effectiveness of gene expression profiling for response prediction of rectal adenocarcinomas to preoperative chemoradiotherapy.
abstract: OBJECTIVE
  There is a wide spectrum of tumor responsiveness of rectal adenocarcinomas to preoperative chemoradiotherapy ranging from complete response to complete resistance. This study aimed to investigate whether parallel gene expression profiling of the primary tumor can contribute to stratification of patients into groups of responders or nonresponders.
  
  
  METHODS
  Pretherapeutic biopsies from 30 locally advanced rectal carcinomas were analyzed for gene expression signatures using microarrays. All patients were participants of a phase III clinical trial (CAO/ARO/AIO-94, German Rectal Cancer Trial) and were randomized to receive a preoperative combined-modality therapy including fluorouracil and radiation. Class comparison was used to identify a set of genes that were differentially expressed between responders and nonresponders as measured by T level downsizing and histopathologic tumor regression grading.
  
  
  RESULTS
  In an initial set of 23 patients, responders and nonresponders showed significantly different expression levels for 54 genes (P < .001). The ability to predict response to therapy using gene expression profiles was rigorously evaluated using leave-one-out cross-validation. Tumor behavior was correctly predicted in 83% of patients (P = .02). Sensitivity (correct prediction of response) was 78%, and specificity (correct prediction of nonresponse) was 86%, with a positive and negative predictive value of 78% and 86%, respectively.
  
  
  CONCLUSIONS
  Our results suggest that pretherapeutic gene expression profiling may assist in response prediction of rectal adenocarcinomas to preoperative chemoradiotherapy. The implementation of gene expression profiles for treatment stratification and clinical management of cancer patients requires validation in large, independent studies, which are now warranted.
authors.affiliation: Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bldg 50, Rm 1408, 50 South Dr, Bethesda, MD 20892-8010, USA.
authors.forename: B Michael
authors.initials: BM
authors.lastname: Ghadimi
authors.forename: Marian
authors.initials: M
authors.lastname: Grade
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Difilippantonio
authors.forename: Sudhir
authors.initials: S
authors.lastname: Varma
authors.forename: Richard
authors.initials: R
authors.lastname: Simon
authors.forename: Cristina
authors.initials: C
authors.lastname: Montagna
authors.forename: Laszlo
authors.initials: L
authors.lastname: Füzesi
authors.forename: Claus
authors.initials: C
authors.lastname: Langer
authors.forename: Heinz
authors.initials: H
authors.lastname: Becker
authors.forename: Torsten
authors.initials: T
authors.lastname: Liersch
authors.forename: Thomas
authors.initials: T
authors.lastname: Ried
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D020869:Gene Expression Profiling; D006801:Humans; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D012334:RNA, Neoplasm / Q000235:genetics* / Q000302:isolation & purification; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology
chemical_list: D012334:RNA, Neoplasm