Figure 1 from Upregulation of an Epithelial miRNA Is Associated with Immune Evasion in Progressive Bronchial Premalignant Lesions
Year: 2026
Type: other
Abstract: Study overview. A, High-quality miRNA-seq data was generated from 156 frozen endobronchial biopsies (n = 28 patients). These samples also had paired mRNA sequencing data. Among the 156 biopsies, 19 adjacent FFPE biopsies, transcriptionally defined as the proliferative molecular subtype, were sectioned and stained to assess spatial localization of key findings. B, The paired miRNA–mRNA sequencing data were used to construct a miRNA–gene network based on database evidence of miRNA target genes and significant negative correlation between miRNA and gene expression patterns (gray circles are miRNAs and red, green, and yellow circles are genes for which the color represents their membership in previously described gene coexpression modules that define PML molecular subtype). Target information was obtained by combining a sequence-based prediction database and experimentally validated databases. Pearson correlation was calculated from expression residuals for each miRNA–mRNA pair, and those with significant negative Pearson correlation coefficients (FDR ≤ 0.05) were selected. Next, we filtered edges to identify miRNAs that may have central gene expression regulatory roles within the miRNA–gene network in each gene module. For each gene module, we identified and retained only the connections from miRNAs for which (i) there are more significantly negative correlated target genes in the module than in other modules (Fisher exact test, odds ratio>1) and (ii) the Fisher-Z–transformed Pearson correlation coefficient densities with its targets within the module were more negative than its targets in other modules (t test, t < 0). miRNAs with significant results from both tests (FDR ≤ 0.05) were considered module-associated miRNAs, and other miRNAs were removed from the network. C–E, For each FFPE biopsy, three consecutive sections were stained for different purposes: (C) H&E to annotate the histologic grades present in the epithelial tissue, (D) chromogenic miRNA-ISH to quantify hsa-miR-149-5p expression and localization, and (E) IMC using 28 metal-tagged antibodies to identify epithelial and immune cell types and hsa-miR-149-5p target protein expression and localization. Single or multiple ROIs per sample were selected for IMC ablation in 14 samples. The epithelial histology in both miRNA-ISH and IMC images was annotated based on the corresponding adjacent H&E section. The schematic was constructed using data images from Fig. 4. [Created in BioRender. Chiu, D. (2026) https://BioRender.com/g78j632]
Authors: Boting Ning, Darren J. Chiu, Roxana M. Pfefferkorn, Erin Cullinane, Yohana Kefella, Erin Kane, Valerie Reyes-Ortiz, Gang Liu, Xiaohui Zhang, Hanqiao Liu, Lila Sultan, Emily Green, Myrtha Constant, Avrum E. Spira, Joshua D. Campbell, Mary E. Reid, Xaralabos Varelas, Eric J. Burks, Marc E. Lenburg, Sarah A. Mazzilli, Jennifer E. Beane
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W7147447002
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