# Identification of LINC02454-related key pathways and genes in papillary thyroid cancer by weighted gene coexpression network analysis (WGCNA)

**Authors:** Yingjian Song, Lin Wang, Yi Ren, Xilei Zhou, Juan Tan

PMC · DOI: 10.1186/s13044-024-00205-8 · Thyroid Research · 2024-09-02

## TL;DR

This study identifies key genes and pathways linked to LINC02454 in papillary thyroid cancer, offering insights into its role in cancer progression.

## Contribution

The study introduces a novel analysis of LINC02454-related pathways and genes in papillary thyroid cancer using WGCNA.

## Key findings

- The turquoise module was most correlated with the clinical stage of papillary thyroid cancer.
- Five key genes (FN1, LAMB3, ITGA3, SDC4, and IL1RAP) were identified as upregulated in thyroid cancer.
- FN1 and ITGA3 were associated with poor disease-free prognosis in thyroid cancer patients.

## Abstract

Our previous study demonstrated that long intergenic noncoding RNA 02454 (LINC02454) may act as an oncogene to promote the proliferation and inhibit the apoptosis of papillary thyroid cancer (PTC) cells. This study was designed to investigate the mechanisms whereby LINC02454 is related to PTC tumorigenesis.

Thyroid cancer RNA sequence data were obtained from The Cancer Genome Atlas (TCGA) database. Weighted gene coexpression network analysis (WGCNA) was applied to identify modules closely associated with PTC. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to identify the key pathways, and the maximal clique centrality (MCC) topological method was used to identify the hub genes. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to compare expression levels of key genes between PTC samples and normal samples and explore the prognostic value of key genes. The key genes were further validated with GEO dataset.

The top 5000 variable genes were investigated, followed by an analysis of 8 modules, and the turquoise module was the most positively correlated with the clinical stage of PTC. KEGG pathway analysis found the top two pathways of the ECM − receptor interaction and MAPK signaling pathway. In addition, five key genes (FN1, LAMB3, ITGA3, SDC4, and IL1RAP) were identified through the MCC algorithm and KEGG analysis. The expression levels of the five key genes were significantly upregulated in thyroid cancer in both TCGA and GEO datasets, and of these five genes, FN1 and ITGA3 were associated with poor disease-free prognosis.

Our study identified five key genes and two key pathways associated with LINC02454, which might shed light on the underlying mechanism of LINC02454 action in PTC.

The online version contains supplementary material available at 10.1186/s13044-024-00205-8.

## Linked entities

- **Genes:** LINC02454 (long intergenic non-protein coding RNA 2454) [NCBI Gene 105369807], FN1 (fibronectin 1) [NCBI Gene 2335], LAMB3 (laminin subunit beta 3) [NCBI Gene 3914], ITGA3 (integrin subunit alpha 3) [NCBI Gene 3675], SDC4 (syndecan 4) [NCBI Gene 6385], IL1RAP (interleukin 1 receptor accessory protein) [NCBI Gene 3556]
- **Diseases:** papillary thyroid cancer (MONDO:0005075), thyroid cancer (MONDO:0002108)

## Full-text entities

- **Genes:** IL1RAP (interleukin 1 receptor accessory protein) [NCBI Gene 3556] {aka C3orf13, IL-1RAcP, IL1R3}, LAMB3 (laminin subunit beta 3) [NCBI Gene 3914] {aka AI1A, BM600-125KDA, JEB1A, JEB1B, LAM5, LAMNB1}, MMRN1 (multimerin 1) [NCBI Gene 22915] {aka ECM, EMILIN4, GPIa*, MMRN}, SDC4 (syndecan 4) [NCBI Gene 6385] {aka SYND4}, ITGA3 (integrin subunit alpha 3) [NCBI Gene 3675] {aka CD49C, FRP-2, GAP-B3, GAPB3, ILNEB, JEB7}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}
- **Diseases:** PTC (MESH:D000077273), Cancer (MESH:D009369), Thyroid cancer (MESH:D013964)

## Full text

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## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11367880/full.md

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Source: https://tomesphere.com/paper/PMC11367880