RESUMO
The early diagnosis of colorectal cancer and the early detection of recurrence are central to effective treatment, as prognosis is directly related to the stage of the disease. When colorectal cancer is diagnosed at an early, localized stage, 5-year survival is 90%. 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 290 tumors and normal tissues revealed that galanin was maximally expressed in colon cancer. These findings were corroborated by real-time quantitative PCR, in which the colon cancer cell lines LOVO, HCT15, SW480, and SW620 cell showed significantly higher levels of galanin expression than did noncolon cancer cell lines. To evaluate galanin as a potential biomarker of colon cancer, a preliminary "training" set of serum from 40 healthy donors and 55 colon cancer patients was analyzed by ELISA. The data pattern was confirmed by an independent set of 90 masked serum samples: 24 from healthy donors and 66 from colon cancer patients. This result yielded a sensitivity of 69.7% [95% confidence interval (95% CI), 57.1-80.4], specificity of 75.0% (95% CI, 53.3-90.2), and positive predictive value of 88.5% (95% CI, 76.6-95.7). The galanin expression level was significantly increased with tumor size and tumor stage. These findings justify a prospective assessment of serum galanin protein as a screening tool for colon cancer.
Assuntos
Adenocarcinoma/sangue , Biomarcadores Tumorais/sangue , Neoplasias do Colo/sangue , Galanina/sangue , Adenocarcinoma/genética , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Feminino , Galanina/biossíntese , Galanina/genética , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Sensibilidade e EspecificidadeRESUMO
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 alpha6 was maximally expressed in colon cancer. These findings were corroborated by reverse transcription-PCR, in which the colon cancer cell lines LoVo, Caco2, HCT-15, SW480, and SW620 showed significantly higher levels of defensin alpha6 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 alpha6 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 enzyme-linked 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 alpha6 protein as a screening tool for colon cancer.