Supplementary MaterialsFIGURE S1: Cross-validation for tuning parameter selection in the LASSO logistical model (A) and SVM-RFE model (B). Supplementary experimental procedures. Data_Sheet_1.docx (27K) GUID:?5D6A35A1-F38F-4603-8DD7-214A9CD6367E Data Availability StatementPublicly available datasets were analyzed in this study. This data can be found at The Cancer Genome Atlas and Gene Expression Omnibus: “type”:”entrez-geo”,”attrs”:”text”:”GSE48267″,”term_id”:”48267″GSE48267 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=”type”:”entrez-geo”,”attrs”:”text”:”GSE48267″,”term_id”:”48267″GSE48267); “type”:”entrez-geo”,”attrs”:”text”:”GSE38389″,”term_id”:”38389″GSE38389 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=”type”:”entrez-geo”,”attrs”:”text”:”GSE38389″,”term_id”:”38389″GSE38389); GSE- 28364 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=”type”:”entrez-geo”,”attrs”:”text”:”GSE28364″,”term_id”:”28364″GSE28364); “type”:”entrez-geo”,”attrs”:”text”:”GSE49246″,”term_id”:”49246″GSE49246 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=”type”:”entrez-geo”,”attrs”:”text”:”GSE49246″,”term_id”:”49246″GSE49246); “type”:”entrez-geo”,”attrs”:”text”:”GSE115513″,”term_id”:”115513″GSE115513 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=”type”:”entrez-geo”,”attrs”:”text”:”GSE115513″,”term_id”:”115513″GSE115513); “type”:”entrez-geo”,”attrs”:”text”:”GSE29622″,”term_id”:”29622″GSE29622 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=”type”:”entrez-geo”,”attrs”:”text”:”GSE29622″,”term_id”:”29622″GSE29622); and TC GA-COAD (https://portal.gdc.cancer.gov/). Abstract Background Colorectal cancer (CRC) is the third most lethal and malignant type of cancer in the world. Abnormal expression of human microRNA-200a (hsa-miRNA-200a or miR-200a) has previously been characterized as a clinically noticeable biomarker in several cancers, but its role in CRC is still unclear. Methods Three CRC miRNA expression datasets were integratively analyzed by Least Absolute Shrinkage and Selector Operation (LASSO) and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) algorithms. Nine candidate miRNAs were identified and validated for diagnostic and prognostic capability with the prediction model. The potential roles of the tumor suppressor miR-200a-3p in invasion, migration, and epithelial-mesenchymal changeover of CRC cells had been elaborated by research. Outcomes Nine miRNAs (miR-492, miR-200a, miR-338, miR-29c, miR-101, miR-148a, miR-92a, miR-424, and miR-210) had been identified as possibly useful diagnostic biomarkers in the center. The overall precision rate from the nine miRNAs in the diagnostic model was 0.94, 0.89, and 0.978 in the tests, validation, and individual validation dataset, respectively. CRC individuals in the “type”:”entrez-geo”,”attrs”:”text message”:”GSE29622″,”term_id”:”29622″GSE29622 cohort had been separated from the prognostic model in to the low-risk rating group as well as the 97682-44-5 high-risk rating group. The region under the recipient operating quality curve (AUC) was 0.872 97682-44-5 and 0.783 for predicting the 1- to 10-yr success of CRC individuals. The performance from the prognostic model was validated by an unbiased TCGA-Colon Adenocarcinoma (COAD) dataset Rabbit Polyclonal to p47 phox with AUC ideals between 0.911 and 0.796 in predicting 1- to 10-yr survival. Nomograms composed of risk ratings, tumor stage, and TNM staging had been produced for predicting 1-, 3-, and 5-yr overall success (Operating-system) in the “type”:”entrez-geo”,”attrs”:”text message”:”GSE29622″,”term_id”:”29622″GSE29622 and TCGA-COAD datasets. Colony development, invasion, and migration in DLD1 and SW480 cells had been suppressed by overexpression of miR-200a-3p. Inhibition of miR-200a-3p function added to irregular colony development, migration, invasion, and epithelialCmesenchymal changeover (EMT). miR-200a-3p binding sites had been located inside the 3-untranslated area (3-UTR) from the Forkhead package protein A1 (FOXA1) mRNA. Conclusion We developed and validated a diagnostic and prognostic prediction model for CRC. miR-200a-3p was determined to be a potential diagnostic and prognostic biomarker for CRC. might be the potential target of miR-200a, regulating YAP-mediated EMT; however, the underlying mechanism in CRC remains unclear. In this four-phase study, we developed a data processing system to solve the curse of dimensionality in high-dimensional gene expression data using LASSO and SVM. Different independent datasets were first integrated by using Fishers method to expand the sample size, and the integrated dataset was then screened for candidate miRNAs of CRC using a prediction model combining the LASSO and SVM models. The full-length 3-UTR of human mRNA was proven for the first time to be a direct target of miR-200a-3p in CRC. A multi-miRNA-based classifier with a logistic regression model was developed for CRC screening or early diagnosis and was validated with the Cox regression model for potential predictors of prognosis. In addition, the results of the present study demonstrate a potential data processing model for identifying novel biomarkers and candidate miRNA patterns in the detection and prognosis prediction of CRC. Materials and Methods Data Collection, Preprocessing, and Normalization Public microarray 97682-44-5 datasets were extracted from the GEO and TCGA database. The checklist and pipeline for proper organization of the integrated analysis were determined following the reporting guidelines of microarray meta-analysis recommended by Ramasamy et al. (2008). Only original experimental studies to screen miRNAs that were differentially expressed (DE) between CRC and ANT in at least 40 human samples were included. Selection criteria, probe annotation, and data normalization were the same 97682-44-5 as described in previous reports (Sun et al., 2017a, b; Lin et al., 2019). 97682-44-5 Integrated Analysis of miRNA Expression Datasets Differentially expressed miRNAs between CRC and ANT were determined by MetaOmics software1 in the MetaDE bundle (Wang et al., 2012). The filtration system thresholds from the mean and SD had been arranged to 30% in built-in analysis. Fishers technique was performed for significant evaluation to counterpoise statistically.