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Serine protease inhibitor Kazal type 1 (SPINK1) as a prognostic marker in stage IV colon cancer patients receiving cetuximab based targeted therapy


Background Serine peptidase inhibitor Kazal type-1 (SPINK1), a trypsin kinase inhibitor, has well established associations with inflammation, cancer cell proliferation and carcinogenesis. However, the role of SPINK1 has not been investigated in stage IV colorectal cancer (CRC) patients receiving cetuximab based targeted therapy. The aim of this study was to evaluate the use of SPINK1 as a biomarker for predicting how patients with end stage CRC respond to anti-epidermal growth factor receptor (EGFR) therapies.

Methods Immunohistochemical staining was used for semiquantitative analysis of SPINK1 protein expression in 51 CRC cases. Expression of SPINK1 protein was then analysed to identify correlations with clinicopathological variables.

Results High SPINK1 expression was significantly associated with males (p=0.018). Kaplan–Meier analyses also showed that patients with high SPINK1 expression had significantly longer overall survival compared with controls (p=0.004). Multivariable analyses showed that SPINK1 expression and tumour size were significantly associated with prognosis (HR 0.416 and 0.437; 95% CI 0.217 to 0.797 and 0.236 to 0.810; p=0.008 and p=0.009, respectively) in these stage IV CRC cases.

Conclusions High SPINK1 expression is associated with a good prognosis in stage IV CRC cases receiving cetuximab based targeted therapy. As SPINK1 expression is also an independent prognostic marker in these patients, it has potential use as a biomarker for clinical decision making and for designing personalised targeted therapies.


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