# Identifying key genes associated with recurrence in non-small cell lung cancer through TCGA and single-cell analysis

**Authors:** Weiyuan Li, Duo Han, Chunxiao Cao, Yuning Xie, Jingxia Shen

PMC · DOI: 10.3389/fmed.2025.1549969 · Frontiers in Medicine · 2025-06-11

## TL;DR

This study identifies key genes linked to lung cancer recurrence using TCGA and single-cell data, highlighting potential targets for treatment.

## Contribution

The study integrates TCGA and single-cell analysis to identify novel genes associated with non-small cell lung cancer recurrence.

## Key findings

- 2,239 and 3,404 differentially expressed genes were identified in LUAD and LUSC datasets, respectively.
- The lapis lazuli module gene set was associated with recurrence, and FOXI1, FOXB1, and KCNA7 were linked to lung cancer progression.
- Metabolism and hormone secretion pathways were found to be key in NSCLC recurrence, with KCNA7 and FOX genes as critical targets.

## Abstract

This study aims to mine the TCGA database for differentially expressed genes in recurrent lung cancer tissues, determine the relationship between these recurrent genes and lung cancer at the single-cell level, and identify potential targets for lung cancer treatment.

Data for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) were obtained from the TCGA database and grouped based on clinical recurrence information. Single-cell data from GSE131907 were downloaded from the GEO database. R was utilized to screen for differentially expressed genes (DEGs), followed by weighted gene co-expression network analysis (WGCNA) of these DEGs. Additionally, the GSEA database was employed to visualize differential pathways and identify key genes. The relationship between the expression of these key genes and lung cancer recurrence was validated using the GSE131907 single-cell dataset.

A total of 2,239 differentially expressed genes were identified in the LUAD dataset, while 3,404 differentially expressed genes were found in the LUSC dataset. WGCNA revealed that the lapis lazuli module gene set was associated with recurrence. Validation at the single-cell level indicated that the FOXI1, FOXB1, and KCNA7 genes were linked to lung cancer progression.

The differentially expressed genes primarily influence NSCLC recurrence through involvement in biological processes related to metabolism and hormone secretion pathways. Notably, the KCNA7 and FOX gene families were identified as critical for NSCLC recurrence. This study highlights specific genes within proliferation and cell cycle pathways as key therapeutic targets for managing NSCLC recurrence.

## Linked entities

- **Genes:** FOXI1 (forkhead box I1) [NCBI Gene 2299], FOXB1 (forkhead box B1) [NCBI Gene 27023], KCNA7 (potassium voltage-gated channel subfamily A member 7) [NCBI Gene 3743]
- **Diseases:** lung cancer (MONDO:0005138), non-small cell lung cancer (MONDO:0005233), lung adenocarcinoma (MONDO:0005061), lung squamous cell carcinoma (MONDO:0005097)

## Full-text entities

- **Genes:** FOXB1 (forkhead box B1) [NCBI Gene 27023] {aka FKH5, HFKH-5}, FOXI1 (forkhead box I1) [NCBI Gene 2299] {aka FKH10, FKHL10, FREAC-6, FREAC6, HFH-3, HFH3}, KCNA7 (potassium voltage-gated channel subfamily A member 7) [NCBI Gene 3743] {aka HAK6, KV1.7}
- **Diseases:** LUAD (MESH:D000077192), lung cancer (MESH:D008175), non-small cell lung cancer (MESH:D002289), LUSC (MESH:D002294)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12187672/full.md

## References

36 references — full list in the complete paper: https://tomesphere.com/paper/PMC12187672/full.md

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Source: https://tomesphere.com/paper/PMC12187672