RESUMEN
Background and objectives: Children with autism spectrum disorder (ASD) present with distinctive clinical features. No objective laboratory assay has been developed to establish a diagnosis of ASD. Considering the known immunological associations with ASD, immunological biomarkers might enable ASD diagnosis and intervention at an early age when the immature brain has the highest degree of plasticity. This work aimed to identify diagnostic biomarkers discriminating between children with ASD and typically developing (TD) children. Methods: A multicenter, diagnostic case-control study trial was conducted in Israel and Canada between 2014 and 2021. In this trial, a single blood sample was collected from 102 children with ASD as defined in Diagnostic Statistical Manual of Mental Disorders [DSM)-IV (299.00) or DSM-V (299.00)], and from 97 typically developing control children aged 3-12 years. Samples were analyzed using a high-throughput, multiplexed ELISA array which quantifies 1,000 human immune/inflammatory-related proteins. Multiple logistic regression analysis was used to obtain a predictor from these results using 10-fold cross validation. Results: Twelve biomarkers were identified that provided an overall accuracy of 0.82 ± 0.09 (sensitivity: 0.87 ± 0.08; specificity: 0.77 ± 0.14) in diagnosing ASD with a threshold of 0.5. The resulting model had an area under the curve of 0.86 ± 0.06 (95% CI: 0.811-0.889). Of the 102 ASD children included in the study, 13% were negative for this signature. Most of the markers included in all models have been reported to be associated with ASD and/or autoimmune diseases. Conclusion: The identified biomarkers may serve as the basis of an objective assay for early and accurate diagnosis of ASD. In addition, the markers may shed light on ASD etiology and pathogenesis. It should be noted that this was only a pilot, case-control diagnostic study, with a high risk of bias. The findings should be validated in larger prospective cohorts of consecutive children suspected of ASD.
RESUMEN
Despite recent advances in molecular profiling of colorectal cancer (CRC), as of yet this has not translated into an unbiased molecular liquid biopsy profile which can accurately screen for early CRC. In this study we depict the profile of early stage CRC as well as for advanced adenomas (AA) by combination of current molecular knowledge with microarray technology, using efficient circulating free plasma RNA purification from blood and RNA amplification technologies. We joined literature search with Affymetrix gene chip experimental procedure to draw the circulating free plasma RNA profile of colorectal cancer disease reflected in blood. The RNA panel was tested by two datasets comparing patients with CRC with healthy subjects and patients with AA to healthy subjects. For the CRC patient cohort (28 CRC cases vs. 41 healthy controls), the ROC analysis of the selected biomarker panel generated a sensitivity of 75% and a specificity of 93% for the detection of CRC using 8-gene classification model. For the AA patient cohort (28 subjects vs. 46 healthy controls), a sensitivity of 60% and a specificity of 87% were calculated using a 2-gene classification model. We have identified a panel of 8 plasma RNA markers as a preliminary panel for CRC detection and subset markers suitable for AA detection. Subjected to extensive clinical validation we suggest that this panel represents a feasible approach and a potential strategy for noninvasive early diagnosis, as a first-line screening test for asymptomatic, average-risk population before colonoscopy.