# Identification of anoikis-related genes in heart failure: bioinformatics and experimental validation

## TL;DR

This study identifies Tln1 and TGFβ2 as key anoikis-related genes in heart failure, suggesting they could be potential therapeutic targets.

## Contribution

The study combines bioinformatics and experimental validation to identify novel anoikis-related genes in heart failure.

## Key findings

- 138 differentially expressed anoikis-related genes were identified in heart failure patients.
- Tln1 and TGFβ2 were confirmed as hub genes involved in heart failure through machine learning and experimental validation.
- Potential drugs targeting TGFβ2 were identified, offering new therapeutic options for heart failure.

## Abstract

Heart failure (HF) is a common clinical syndrome caused by ventricular dysfunction and one of the leading causes of mortality worldwide. Previous studies have suggested that anoikis is relevant to HF. This study aimed to identify hub genes associated with anoikis that may offer therapeutic targets for HF.

Gene expression data for GSE36074 were obtained from the Gene Expression Omnibus (GEO) and anoikis-related genes (ARGs) were extracted from GeneCards. GEO2R was used to screen for differentially expressed genes (DEGs), then by overlapping DEGs with ARGs, differentially expressed ARGs (DEARGs) were screened. The biological functions of the DEARGs were determined using DAVID. Subsequently, two machine learning (ML) algorithms were employed to identify hub DEARGs: least absolute shrinkage and selection operator (LASSO) and random forest (RF). In addition, miRNA-hub DEARGs and drug-hub DEARGs networks were constructed. Lastly, the hub DEARGs were validated by quantitative reverse transcription PCR (RT-qPCR) and Immunofluorescence (IF).

A total of 138 DEARGs were identified in GSE36074. Functional analysis of DEARGs revealed that they were primarily enriched in the positive regulation of the apoptotic process, PI3K-Akt, and FoxO signaling pathways. Subsequently, two hub DEARGs (Tln1 and TGFβ2) were screened using LASSO and RF algorithms. According to the miRNA–hub DEARGs networks, Tln1 and TGFβ2 were regulated by 34 and 68 miRNAs, respectively. Moreover, drug-hub DEARGs networks showed that Gemogenovatucel-t, Lerdelimumab, Belagenpumatucel-l, Fresolimumab, Bintrafusp alfa, Trabedersen and Luspatercept-aamt are potential drugs that could target TGFβ2. Finally, RT-qPCR and IF validation of two key DEARGs (Tln1 and TGFβ2) supported our bioinformatics analysis.

These findings suggest that Tln1 and TGFβ2 may play important roles in HF development through the regulation of anoikis and may serve as therapeutic targets for HF.

Not applicable.

The online version contains supplementary material available at 10.1186/s41065-025-00532-2.