Identification of Defensin 6 as a Potential Biomarker in Colon Adenocarcinoma*

There is substantial interest in the identification of circulating human tumor-derived proteins in serum for the purposes of early cancer diagnosis. We have implemented an approach based on the analysis of microarray data for the identification of tumor proteins that may have utility as biomarkers in colon cancer. Expression analysis of microarray data obtained from a variety of 283 tumors and normal tissues revealed that defensin 6 was maximally expressed in colon cancer. These findings were corroborated by reverse transcription-PCR, in which the colon cancer cell lines LoVo, Caco2, HCT15, SW480, and SW620 showed significantly higher levels of defensin 6 expression than did non-colon cancer cell lines. Moreover, our data were concordant with data obtained from the NCI, National Institutes of Health Cancer Genome Anatomy Project. To evaluate defensin 6 as a potential biomarker of colon cancer, a preliminary “training” set of serum from 91 healthy donors and 109 colon cancer patients was analyzed by enzymelinked immunosorbent assay. The data pattern was confirmed by an independent set of 67 masked serum samples: 18 from healthy donors and 49 from colon cancer patients. This result yielded a sensitivity of 69.4% (95% CI 54.6–81.8), specificity of 83.3% (58.6–96.4), and positive predictive value of 91.9% (78.1–98.3). These findings justify a prospective assessment of serum defensin 6 protein as a screening tool for colon cancer.