January 2009: Volume 35, Number 1
New Panel of Fecal Protein Biomarkers for CRC Identified
A novel combination of fecal protein biomarkers demonstrated higher sensitivity and specificity than iFOBT alone in detecting colorectal cancer. If validated in further studies, use of these markers could help improve compliance with and accuracy of colorectal cancer screening programs (Clin Gastroenterol Hepatol 2008; 6:1122–1128). The goal of the study was to improve early detection of CRC in stool samples. iFOBT assays are more effective than guaiac-based FOBT, but still miss about one-third of cancer cases.
Researchers had found through previous research that the fecal marker S100A12 had increased expression in colorectal cancer. In this study, they evaluated the diagnostic performance of S100A12, along with five other stool markers, including hemoglobin, hemoglobin-haptoglobin, calprotectin, carcinoembryogenic antigen (CEA), and tissue inhibitor of metalloproteinase-1 (TIMP-1), alone and in combination, in a collection of 551 stool samples, divided into three groups based on clinical classification. Using univariate analysis researchers found that S100A12 had the best discrimination for CRC, followed by TIMP-1, hemoglobin-haptoglobin, hemoglobin, and calprotectin. CEA did not demonstrate diagnostically significant discriminatory power. Using multi-variate analysis, the best sensitivity of 82% and specificity of 98% resulted from a combination of S100A12, hemoglobin-haptoglobin, and TIMP-1. This combination had the highest increase in sensitivity in early tumor stages. The results demonstrate a “significant improvement” in the early diagnosis of CRC, according to the authors. They plan to further evaluate the use of combined S100A12, hemoglobin-haptoglobin, and TIMP-1 results as a threshold to trigger follow-up colonoscopy, in a multicenter study.
Biomarker Panel Could Help Identify Progression of Esophageal Dysplasia
An analysis of genes differentially expressed in high-grade esophageal dysplasia (HGD) versus nondysplastic Barrett’s Esophagus (NDBE) revealed that 131 genes are over-expressed by at least 2.5 fold in HGD versus NGDE, and 16 genes are under-expressed by at least the same amount (Clin Cancer Res 2008; 14:6440–6448). This innovative study is the first to employ laser capture microdissection (LCM) of HGD and BE epithelial cells followed by microarray analysis specifically designed to analyze material from formalin-fixed, paraffin-embedded (FFPE) samples. It lays the groundwork for identifying a panel of biomarkers that would help identify patients most likely to progress from NDBE to esophageal adenocarcinoma, and that would aide physicians in better distinguishing between grades of dysplasia.
Researchers used LCM to isolate epithelial cells from areas of both HGD and NDBE in FFPE tissues from 11 patients. They extracted and amplified mRNA from laser-captured cells, then reverse-transcribed the mRNA and applied it on Affymetrix cDNA microarray chips customized for formalin-exposed tissue. Researchers employed real-time PCR and immunohistochemistry analyses to confirm differential gene expression. This process identified 157 differentially expressed genes from various gene function categories.
Some of the genes found to be either over- or under-expressed had been shown in previous analyses to be modified in the progression from BE to EAC, but this study identified several novel markers. Researchers plan to extend the study by including additional cases and examining whether any of the markers predict progression for NDBE to esophageal adenocarcinoma.