Effects of radiation therapy on tissue and serum concentrations of tumour associated trypsin inhibitor and their prognostic significance in rectal cancer patients

Radiation Oncology

Karin Jirström⁴  Louis B Johnson³  Bengt Jeppsson³  Ulf-Håkan Stenman¹  Anders Bjartell²  Ingrid Palmquist³  Björn Nodin⁴  Kristina Hotakainen¹  Christina Stene³  Alexander Gaber⁴ 

[1] Department of Clinical Chemistry, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland;Department of Clinical Sciences, Division of Urological Cancers, Lund University, Skåne University Hospital, Malmö, Sweden;Department of Clinical Sciences, Division of Colorectal Surgery, Lund University, Skåne University Hospital, Malmö, Sweden;Department of Clinical Sciences, Division of Pathology, Lund University, Skåne University Hospital, Lund, Sweden

关键词: biomarker;    prognosis;    radio therapy;    TATI;    tissue micro array;    Rectal cancer;   

Others  :  1223915
DOI  :  10.1186/1748-717X-6-100

 received in 2011-05-03, accepted in 2011-08-24,  发布年份 2011

【 摘 要 】

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.

【 授权许可】

   
2011 Gaber et al; licensee BioMed Central Ltd.

【 图 表 】

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