Identification of a biomarker panel for colorectal cancer diagnosis

Abstract

BackgroundMalignancies arising in the large bowel cause the second largest number of deaths from cancer in the Western World. Despite progresses made during the last decades, colorectal cancer remains one of the most frequent and deadly neoplasias in the western countries.MethodsA genomic study of human colorectal cancer has been carried out on a total of 31 tumoral samples, corresponding to different stages of the disease, and 33 non-tumoral samples. The study was carried out by hybridisation of the tumour samples against a reference pool of non-tumoral samples using Agilent Human 1A 60-mer oligo microarrays. The results obtained were validated by qRT-PCR. In the subsequent bioinformatics analysis, gene networks by means of Bayesian classifiers, variable selection and bootstrap resampling were built. The consensus among all the induced models produced a hierarchy of dependences and, thus, of variables.ResultsAfter an exhaustive process of pre-processing to ensure data quality--lost values imputation, probes quality, data smoothing and intraclass variability filtering--the final dataset comprised a total of 8, 104 probes. Next, a supervised classification approach and data analysis was carried out to obtain the most relevant genes. Two of them are directly involved in cancer progression and in particular in colorectal cancer. Finally, a supervised classifier was induced to classify new unseen samples.ConclusionsWe have developed a tentative model for the diagnosis of colorectal cancer based on a biomarker panel. Our results indicate that the gene profile described herein can discriminate between non-cancerous and cancerous samples with 94.45% accuracy using different supervised classifiers (AUC values in the range of 0.997 and 0.955).

Risk Prediction Models for Colorectal Cancer: A Systematic Review

“…1). Four were excluded as they included circulating biomarkers that were felt to detect prevalent undiagnosed disease rather than estimate future risk (11)(12)(13)(14).…”

Circulating midkine in malignant and non-malignant colorectal diseases

“…Admittedly, FOBT is non-expensive and non-invasive, but lacks required diagnostic power and its sensitivity depends on tumor location. In turn, colonoscopy, the only available surveillance tool in IBD, and other imaging techniques are expensive, invasive and bear a risk for bowel bleeding and perforation [8].…”

Quantitative proteomic profiling of paired cancerous and normal colon epithelial cells isolated freshly from colorectal cancer patients

“…Of these, 19 proteins (31.1%) were associated with colorectal cancer, including S100-A8, S100-A9, defensin 1, and fibronectin that have been identified as serological markers of colorectal cancer [35–37]. Because of the heterogeneity of CRC, a panel of screening biomarkers was expected to achieve better sensitivity for clinical prognosis than individual markers [38, 39]. The elevated proteins identified here that are common among at least 90% of patients of various stages may constitute an enhanced biomarker panel for the diagnosis of CRC.…”