title: Molecular changes consistent with increased proliferation and invasion are common in rectal cancer.
abstract: BACKGROUND Survival in rectal cancer remains unchanged despite improved treatment modalities. Molecular biology may hold the key to new strategies. Gene expression abnormalities need identification in tumour specimens to identify targets for therapy. The impact of neoadjuvant therapy on induced gene expression changes needs to be assessed to distinguish the intrinsic tumour-specific changes from those changes that may be induced by neoadjuvant therapy. METHODS Gene expression changes were examined in 21 rectal tumours plus matched normal mucosa and cells exposed to 5-FU and gamma radiation, using DNA membrane arrays. These arrays contained 100 genes in common cancer pathways. The most commonly up-regulated gene, c-FOS, was quantified using real-time PCR. RESULTS c-FOS was the most commonly up-regulated gene, occurring in 7 of 21 samples (33%), all samples having a greater than 2-fold increase. SERPINE-1 was the second most commonly up-regulated gene with 6 of 21 samples showing up-regulation (29%). There was no clear correlation between up-regulation of c-FOS or SERPINE-1 and clinico-pathological data. Neither c-FOS nor SERPINE-1 gene expression was induced by 5-FU treatment or gamma irradiation in vitro, but MUC 18 was up-regulated by 5-FU treatment. This suggests that FOS and SERPINE-1 expression changes are specific to the tumour and will not arise as artefacts of neoadjuvant therapy. CONCLUSION The study suggests that c-FOS and SERPINE-1 may have important but as yet unclear roles in the tumour biology of rectal cancer but probably only represent a small part of the complex molecular biology of rectal cancer.
authors.affiliation: Department of Colorectal Surgery, Singleton Hospital, Swansea, UK.
authors.forename: R
authors.initials: R
authors.lastname: Hughes
authors.forename: J
authors.initials: J
authors.lastname: Parry
authors.forename: J
authors.initials: J
authors.lastname: Beynon
authors.forename: G
authors.initials: G
authors.lastname: Jenkins
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects* / Q000528:radiation effects*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D005720:Gamma Rays; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D011379:Prognosis; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D012007:Rectum / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D017395:Plasminogen Activator Inhibitor 1; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; C051321:SERPINE1 protein, human; D005472:Fluorouracil