Integrated dysregulation of RNF43 and associated lncRNAs reveals transcriptional remodeling in colorectal carcinoma

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The Wnt signaling cascade is crucial for diverse biological processes, including cell cycle regulation, inflammation, embryonic development, and tumorigenesis. The present study investigates the expression of TSPOAP1-AS1, TMEM147-AS1, and FOXP4-AS1 lncRNAs, along with RNF43, all of which are associated with the Wnt/β-catenin signaling pathway, in colorectal cancer (CRC) samples compared to adjacent normal tissues (ANTs). RNF43 was significantly overexpressed in CRC samples, with a median 2.34-fold increase relative to normal tissues (P value = 0.04). In contrast, the lncRNA TSPOAP1-AS1 was markedly down-regulated in tumors, showing a median 0.42-fold reduction (P value = 0.03). The remaining two lncRNAs—TMEM147-AS1 and FOXP4-AS1—were also significantly elevated, exhibiting median fold-changes of 2.94-fold (P value < 0.0001) and 2.02-fold (P value = 0.003), respectively. All four transcripts achieved exceptionally high specificity (97.5–100%) but only moderate sensitivity (29.3–56.1%) for discrimination of CRC samples from ANTS, reflecting their stringent discrimination of ANTs at the expense of missing a subset of tumors. Taken together, our results revealed a coordinated dysregulation of Wnt-related genes in CRC, i.e. loss of TSPOAP1-AS1 alongside gain of RNF43, TMEM147-AS1, and FOXP4-AS1 expression, highlighting their potential as complementary biomarkers.

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