Whole transcriptome analysis identifies ALB-EEF1A1 fusion as a novel biomarker in metastatic colorectal cancer

IF 2.8

Cancer pathogenesis and therapy Pub Date : 2025-02-04 DOI:10.1016/j.cpt.2025.02.002

Deeksha Rikhari , Ankit Srivastava , Sandhya Rai , Mubashra , Srinivas Patnaik , Sameer Srivastava

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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.

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全转录组分析发现ALB-EEF1A1融合是转移性结直肠癌的一种新的生物标志物

结直肠癌（CRC）是一种复杂的异质性疾病，其特点是经常复发和转移。先前的研究报道，在一些病例中，CRC的侵袭和进展可以通过靶向融合基因来控制。本研究旨在筛选有效的融合转录物作为转移性CRC （mCRC）的潜在分子生物标志物和治疗靶点。方法对18例原发性结直肠癌患者的srna测序（RNA-seq）数据以及匹配的正常和轻度结直肠癌样本进行分析。使用Kallisto和Pizzly软件筛选新的融合转录本，然后进行基因本体（Gene Ontology， GO）、途径分析、转录因子富集和存活功能富集分析。此外，融合转录物作为生物标志物的效用使用泛癌症分析进行了评估。结果共鉴定出32个mCRC特有的融合基因。Hub基因分析鉴定出17个新的融合转录本，GO分析显示这些基因具有不同的生物学和分子功能。与结直肠癌显著相关的通路包括补体和凝血级联、铁凋亡、白细胞介素-17 （IL-17）信号通路和雌激素信号通路。基于显著的基因表达和生存结果，我们发现白蛋白-真核翻译延伸因子1 α 1 （ALB-EEF1A1）是mCRC独有的。此外，其作为预后生物标志物的效用通过泛癌症分析得到证实。结论salb - eef1a1可能在原发性结直肠癌的转移转化中起关键作用，并显著增加死亡风险。已确定的ALB-EEF1A1融合转录本是有希望的新分子靶点，可能在未来作为mCRC的预后和诊断生物标志物和治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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