title: Effects of radiation therapy on tissue and serum concentrations of tumour associated trypsin inhibitor and their prognostic significance in rectal cancer patients.
abstract: BACKGROUND
  We have previously demonstrated that elevated concentrations of tumour-associated trypsin inhibitor (TATI) in both tumour tissue (t-TATI) and in serum (s-TATI) are associated with a poor prognosis in colorectal cancer patients. It was also found that s-TATI concentrations were lower in patients with rectal cancer compared to patients with colon cancer. In this study, we investigated the effects of neoadjuvant radiotherapy (RT) on concentrations of t-TATI and s-TATI in patients with rectal cancer.
  
  
  METHODS
  TATI was analysed in serum, normal mucosa and tumour tissue collected at various time points in 53 rectal cancer patients enrolled in a case-control study where 12 patients received surgery alone, 20 patients 5 × 5 Gy (short-term) preoperative RT and 21 patients 25 × 2 Gy (long-term) preoperative RT. T-TATI was analysed by immunohistochemistry and s-TATI was determined by an immunofluorometric assay. Mann-Whitney U test and Wilcoxon Z (Z) test were used to assess t-TATI and s-TATI concentrations in relation to RT. Spearman's correlation (R) test was used to explore the associations between t-TATI, s-TATI and clinicopathological parameters. Overall survival (OS) according to high and low t-TATI and s-TATI concentrations was estimated by classification and regression tree analysis, Kaplan-Meier analysis and the log rank test.
  
  
  RESULTS
  RT did not affect concentrations of t-TATI or s-TATI. In patients receiving short-term but not long-term RT, s-TATI concentrations were significantly higher 4 weeks post surgery than in serum drawn prior to surgery (Z = -3.366, P < 0.001). T-TATI expression correlated with male gender (R = 0.406, P = 0.008). High t-TATI expression in surgical specimens was associated with a significantly shorter OS (P = 0.045). S-TATI concentrations in serum drawn at all time points were associated with an impaired OS (P = 0.035 before RT, P = 0.001 prior to surgery, P = 0.043 post surgery). At all time points, s-TATI correlated with higher age (P < 0.001-0.021) and with increased s-creatinine concentrations assessed prior to surgery (P = 0.041).
  
  
  CONCLUSIONS
  The results presented here further validate the utility of t-TATI and s-TATI as prognostic biomarkers in patients with rectal cancer, independent of neoadjuvant RT.
authors.affiliation: Department of Clinical Sciences, Division of Pathology, Lund University, Skåne University Hospital, Lund, Sweden.
authors.forename: Alexander
authors.initials: A
authors.lastname: Gaber
authors.forename: Christina
authors.initials: C
authors.lastname: Stene
authors.forename: Kristina
authors.initials: K
authors.lastname: Hotakainen
authors.forename: Björn
authors.initials: B
authors.lastname: Nodin
authors.forename: Ingrid
authors.initials: I
authors.lastname: Palmquist
authors.forename: Anders
authors.initials: A
authors.lastname: Bjartell
authors.forename: Ulf-Håkan
authors.initials: UH
authors.lastname: Stenman
authors.forename: Bengt
authors.initials: B
authors.lastname: Jeppsson
authors.forename: Louis B
authors.initials: LB
authors.lastname: Johnson
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012372:ROC Curve; D011878:Radiotherapy / Q000379:methods*; D012004:Rectal Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000378:metabolism* / Q000532:radiotherapy*; D012044:Regression Analysis; D016896:Treatment Outcome; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000096:biosynthesis* / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D014359:Trypsin Inhibitor, Kazal Pancreatic