# IFI35 and IFIT3 are potentially important biomarkers for early diagnosis and treatment of esophageal squamous cell carcinoma: based on WGCNA and machine learning analysis

**Authors:** Hao Wu, Liang Yang, Xiaokun Weng

PMC · DOI: 10.3389/fgene.2025.1583202 · Frontiers in Genetics · 2025-05-20

## TL;DR

This study identifies IFIT3 and IFI35 as potential biomarkers for early diagnosis and treatment of esophageal squamous cell carcinoma using gene analysis and machine learning.

## Contribution

The study introduces IFIT3 and IFI35 as novel biomarkers for ESCC diagnosis and treatment through WGCNA and machine learning.

## Key findings

- 1,019 genes were identified as associated with ESCC through DEGs and co-expression analysis.
- IFIT3 and IFI35 were selected as key biomarkers with reliable diagnostic performance confirmed by ROC analysis.
- Differences in immune cell infiltration were observed in relation to the identified genes.

## Abstract

Esophageal squamous cell carcinoma (ESCC) does not have distinct and highly sensitive biomarkers, making its diagnosis difficult. Consequently, identifying dependable biomarkers is critical, as these indicators can facilitate accurate ESCC diagnosis and enable effective prognostic evaluation.

ESCC datasets (GSE29001, GSE20347, GSE45670, and GSE161533) were sourced from the GEO, and the Limma package identified differentially expressed genes (DEGs). To characterize co-expression network, weighted gene co-expression network analysis (WGCNA) was performed, allowing for the identification of relevant co-expression modules. To assess the biological pathways of intersecting genes, we performed pathway enrichment analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). The Support Vector Machine Recursive Feature Elimination (SVM), along with Least Absolute Shrinkage and Selection Operator (LASSO) regression, was applied to identify clinical biomarkers. Finally, the differences of immune cell infiltration were also detected.

1,019 genes were derived by integrating DEGs with co-expressed module genes. KEGG and GO revealed a strong association between these genes and processes such as chemotaxis and IL−17 signaling pathways. Two hub genes (IFIT3 and IFI35) were selected through LASSO regression and SVM. Additionally, ROC curve analysis confirmed their potential for reliable diagnostic performance. Furthermore, differences in immune cell infiltration were observed.

Collectively, IFIT3 and IFI35 emerged as promising candidate biomarkers, offering novel insights to enhance early detection and guide targeted treatment strategies for ESCC.

## Linked entities

- **Genes:** IFI35 (interferon induced protein 35) [NCBI Gene 3430], IFIT3 (interferon induced protein with tetratricopeptide repeats 3) [NCBI Gene 3437]
- **Diseases:** esophageal squamous cell carcinoma (MONDO:0005580)

## Full-text entities

- **Genes:** IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, IFIT3 (interferon induced protein with tetratricopeptide repeats 3) [NCBI Gene 3437] {aka CIG-49, GARG-49, IFI60, IFIT4, IRG2, ISG60}, IFI35 (interferon induced protein 35) [NCBI Gene 3430] {aka IFP35}
- **Diseases:** ESCC (MESH:D000077277)

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12129983/full.md

## References

37 references — full list in the complete paper: https://tomesphere.com/paper/PMC12129983/full.md

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Source: https://tomesphere.com/paper/PMC12129983