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Published on: June 2, 2023
Clinical Significance, Immune Infiltration Landscape, and Functional Network Analysis of miR-192-5p in Colorectal
Abstract:
Colorectal cancer (CRC) is a heterogeneous malignancy in which microRNAs may contribute to tumor progression and biomarker discovery. This study evaluated the clinical significance, immune associations, and functional network of miR-192-5p in CRC by integrating TCGA/GDC and GEO bioinformatic analyses, paired tissue qRT-PCR validation, target prediction, immune signature analysis, and HT29 wound-healing experiments. Reanalysis of TCGA/GDC miRNA-seq data included 616 tumor and 11 normal COADREAD samples and showed higher database-level hsa-mir-192 signal in tumor samples than in normal samples (Mann-Whitney p = 9.96 x 10-8). The same direction was observed in 11 paired TCGA cases (median tumor-normal difference = 3.13 log2[RPM + 1], Wilcoxon p = 0.0029), whereas local qRT-PCR in paired clinical tissues supported lower mature miR-192-5p expression in CRC tissues. TCGA-based ROC analysis showed strong tumor-normal separation, but balanced resampling and leave-one-normal-out analyses confirmed that this result should be interpreted cautiously due to the limited number of normal samples. Clinicopathological analysis suggested associations with N stage and age in the TCGA cohort, whereas T stage and M stage were not significant in the summarized table, and overall survival analysis did not show a significant prognostic association. Candidate hub-gene analyses using TCGA RNA-seq provided exploratory expression, correlation, and survival evidence but did not establish direct miR-192-5p targeting. Immune signature analysis showed heterogeneous, mostly weak correlations. Functionally, miR-192-5p mimic transfection reduced HT29 wound closure. These findings indicate that miR-192-5p is biologically relevant to CRC, but its expression direction and clinical interpretation are platform-dependent and require further experimental validation.