Gene expression profiles from blood can differentiate patients with CD from those with UC and from noninflammatory diarrheal disorders.

BackgroundColonoscopy is widely regarded to be the gold standard for colorectal cancer (CRC) detection. Recent studies, however, suggest that the effectiveness of colonoscopy is mostly confined to tumors on the left side of the colon (descending, sigmoid, rectum), and that the technology has poor tumor detection for right-sided (cecum, ascending, transverse) lesions. A minimally invasive test that can detect both left-sided and right-sided lesions could increase the effectiveness of screening colonoscopy by revealing the potential presence of neoplasms in the right-sided “blind spot”.MethodsWe previously reported on a seven-gene, blood-based biomarker panel that effectively stratifies a patient’s risk of having CRC. For the current study, we assessed the effectiveness of the seven-gene panel for the detection of left- and right-sided CRC lesions. Results were evaluated for 314 patients with CRC (left-sided: TNM I, 65; TNM II, 57; TNM III, 60; TNM IV, 17; unknown, 9. right-sided: TNM I, 28; TNM II, 29; TNM III, 38; TNM IV, 12; unknown, 1 and including two samples with both left and right lesions) and 328 control samples. Blood samples were obtained prior to clinical staging and therapy. Most CRC subjects had localized disease (stages I and II, 58%); regional (stage III) and systemic (stage IV) disease represented 32% and 9%, respectively, of the study population.ResultsThe panel detected left-sided (74%, 154/208) and right-sided (85%, 92/108) lesions with an overall sensitivity of 78% (215/316) at a specificity of 66% (215/328). Treatable cancer (stages I to III) was detected with left-sided lesion sensitivity of 76% (138/182) and right-sided sensitivity of 84% (80/95).ConclusionThis seven-gene biomarker panel detected right-sided CRC lesions across all cancer stages with a sensitivity that is at least equal to that for left-sided lesions. This study supports the use of this panel as the basis for a patient-friendly, blood-based test that can be easily incorporated into a routine physical examination in advance of colonoscopy to provide a convenient companion diagnostic and a pre-screening alert, ultimately leading to enhanced CRC screening effectiveness.

e15037 Background: Blood participates in physiological and pathological changes throughout the body which are reflected as changes in cellular gene expression. The involvement of the immune system in cancer suppression and promotion through immunoediting exemplifies this. These characteristics make blood a promising non-invasive surrogate tissue for cancer diagnosis and monitoring. Methods: A multi-class cancer classification model, Aristotle, was developed with logistic regression using Affymetrix gene expression profiles generated from 2,845 unique human whole peripheral blood samples. The model was evaluated through 100 iterations of 2-fold cross-validation. Results: The 1,013 cancer patient samples (age 61±13, 40.6% ♀), include cancer of the bladder (n = 87, age 65±11, 23.3% ♀), breast (n = 94, age 54±10, 98.4% ♀), colon (n = 205, age 64±13, 39.5% ♀)/colon polyps (n = 226, age 61±11, 36.0% ♀), cervix (n = 36, age 55±13), endometrium (n = 25, age 49±12), liver (n = 16, age 57±11, 12.5% ♀), nasopharynx (n = 78, age 51±13, 26.9% ♀), ovaries (n = 64, age 55±12), prostate (n = 160, age 68±9) or stomach (n = 22, age 59±11, 28.6% ♀); and 1,832 control samples (age 53±16, 38.9% ♀), including healthy subjects (n = 1,042, age 55±16, 37.0 ♀) and subjects with ankylosing spondylitis (n = 59, age 39±12, 18.6% ♀), heart failure (n = 193, age 67±12, 40.0% ♀), inflammatory bowel disease (n = 51, age 37±9, 40.0% ♀), osteoarthritis (n = 248, age 53±15, 45.6% ♀), rheumatoid arthritis (n = 40, age 57±17, 84.6% ♀), schizophrenia (n = 110, age 36±13, 43.6% ♀) or other (n = 89, age 50±14, 41.1% ♀). Aristotle classified cancer profiles with sensitivities from 55.6-100% and positive predictive values from 5.6-77.7% at a specificity of 99.0% (Table). The mean false positive rate for the 11 cancer classes ranged from 0.3- 6.8%. Conclusions: Our study demonstrates the clinical viability of using whole peripheral blood for multi-class cancer classification. Aristotle was capable of classifying patients with different types of cancer with clinically relevant accuracy. We are confident that Aristotle holds great promise to help address the need for practical and non-invasive early-stage cancer diagnostics. [Table: see text]