title: Preoperative chemoradiotherapy in locally advanced rectal cancer: correlation of a gene expression-based response signature with recurrence.
abstract: Preoperative chemoradiotherapy is recommended for locally advanced rectal cancer (UICC stage II/III). We recently demonstrated that responsive and nonresponsive tumors showed differential expression levels of 54 genes. In this follow-up study, we investigated the relationship between this gene set and disease-free (DFS) and overall survival (OS). Pretherapeutic biopsies from 30 participants in the CAO/ARO/AIO-94 trial of the German Rectal Cancer Study Group were analyzed using gene expression microarrays. Statistical analysis was performed to identify differentially expressed genes between recurrent and nonrecurrent tumors and to correlate these changes with disease recurrence and outcome. After a median follow-up of 59 months, seven of eight patients with recurrent disease was a nonresponder, and one responsive tumor recurred. Response to chemoradiotherapy was significantly correlated with an improved DFS (log rank P=0.028), whereas OS did not differ significantly (P=0.11). Applying a class comparison analysis, we identified 20 genes that were differentially expressed between recurrent and nonrecurrent tumors (P<0.001). Analyzing the first two principal components of the 54 genes previously identified to predict response, we observed that this response signature correlated with an increased risk of cancer recurrence. These data suggest that the genetic basis of local response also affects the genetic basis of tumor recurrence. Genes that are indicative of nonresponse to preoperative chemoradiotherapy might also be linked to an increased risk of tumor recurrence.
authors.affiliation: Department of General and Visceral Surgery, University Medical Center, Georg-August-University, Robert Koch Str. 40, 37075 Göttingen, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Liersch
authors.forename: Marian
authors.initials: M
authors.lastname: Grade
authors.forename: Jochen
authors.initials: J
authors.lastname: Gaedcke
authors.forename: Sudhir
authors.initials: S
authors.lastname: Varma
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Difilippantonio
authors.forename: Claus
authors.initials: C
authors.lastname: Langer
authors.forename: Clemens F
authors.initials: CF
authors.lastname: Hess
authors.forename: Heinz
authors.initials: H
authors.lastname: Becker
authors.forename: Thomas
authors.initials: T
authors.lastname: Ried
authors.forename: B Michael
authors.initials: BM
authors.lastname: Ghadimi
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000601:surgery / Q000628:therapy*; D011300:Preoperative Care; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000235:genetics / Q000601:surgery / Q000628:therapy*
chemical_list: D014408:Biomarkers, Tumor