Abstract
BACKGROUND: Colorectal cancer (CRC) is a complex, heterogeneous disease characterized by frequent relapses and metastasis. Previous studies have reported that the invasion and progression of CRC in several cases can be controlled by targeting fusion genes. This study aimed to screen for potent fusion transcripts as potential molecular biomarkers and therapeutic targets for metastatic CRC (mCRC) using an in silico approach. METHODS: RNA sequencing (RNA-seq) data from 18 patients with primary CRC and matched normal and mCRC samples were derived from the same patient set. Novel fusion transcripts were screened using the Kallisto and Pizzly software, followed by Gene Ontology (GO), pathway analysis, transcription factor enrichment, and survival for functional enrichment analysis. Furthermore, the fusion transcripts' utility as biomarkers was evaluated using a pan-cancer analysis. RESULTS: In total, 32 fusion genes unique to mCRC were identified. Hub gene analysis identified 17 novel fusion transcripts, and GO analysis revealed that these genes were enriched in different biological and molecular functions. Pathways significantly correlated with CRC included the complement and coagulation cascades, ferroptosis, interleukin-17 (IL-17) signaling pathway, and estrogen signaling pathway. We identified albumin-eukaryotic translation elongation factor 1 alpha 1 (ALB-EEF1A1) as unique to mCRC based on significant gene expression and survival outcomes. Moreover, its utility as a prognostic biomarker was confirmed using a pan-cancer analysis. CONCLUSIONS: ALB-EEF1A1 may play a pivotal role in the metastatic transformation of primary CRC and significantly increase the risk of death. The identified ALB-EEF1A1 fusion transcripts are promising novel molecular targets that may serve as prognostic and diagnostic biomarkers and treatment targets for mCRC in the future.