# Integrating machine learning and single-cell sequencing to identify shared biomarkers in type 1 diabetes mellitus and clear cell renal cell carcinoma

**Authors:** Yi Li, Rui Zeng, Yuhua Huang, Yumin Zhuo, Jun Huang

PMC · DOI: 10.3389/fonc.2025.1543806 · 2025-03-03

## TL;DR

This study uses machine learning and single-cell sequencing to find shared biomarkers between type 1 diabetes and kidney cancer, aiming to improve early detection and treatment.

## Contribution

The study identifies three shared hub genes between T1DM and ccRCC using machine learning and single-cell data, offering new biomarkers for early detection and treatment.

## Key findings

- Three hub genes (KIF21A, PIGH, RPS6KA2) were identified as shared between T1DM and ccRCC.
- KIF21A and PIGH were downregulated, while PIGH was upregulated in disease groups.
- The MIF signaling pathway may be related to these hub genes.

## Abstract

Type 1 diabetes mellitus (T1DM), as an autoimmune disease, can increase susceptibility to clear cell renal cell carcinoma (ccRCC) due to its proinflammatory effects. ccRCC is characterized by its subtle onset and unfavorable prognosis. Thus, the aim of this study was to highlight prevention and early detection opportunities in high-risk populations by identifying common biomarkers for T1DM and ccRCC.

Based on multiple publicly available datasets, WGCNA was applied to identify gene modules closely associated with T1DM, which were then integrated with prognostic DEGs in ccRCC. Subsequently, the LASSO and SVM algorithms were employed to identify shared hub genes between the two diseases. Additionally, clinical samples were used to validate the expression patterns of these hub genes, and scRNA-seq data were utilized to analyze the cell types expressing these genes and to explore potential mechanisms of cell communication.

Overall, three hub genes (KIF21A, PIGH, and RPS6KA2) were identified as shared biomarkers for TIDM and ccRCC. Analysis of clinical samples and multiple datasets revealed that KIF21A and PIGH were significantly downregulated and that PIG was upregulated in the disease group. KIF21A and PIGH are mainly expressed in NK and T cells, PRS6KA2 is mainly expressed in endothelial and epithelial cells, and the MIF signaling pathway may be related to hub genes.

Our results demonstrated the pivotal roles of hub genes in T1DM and ccRCC. These genes hold promise as novel biomarkers, offering potential avenues for preventive strategies and the development of new precision treatment modalities.

## Linked entities

- **Genes:** KIF21A (kinesin family member 21A) [NCBI Gene 55605], PIGH (phosphatidylinositol glycan anchor biosynthesis class H) [NCBI Gene 5283], RPS6KA2 (ribosomal protein S6 kinase A2) [NCBI Gene 6196]
- **Diseases:** type 1 diabetes mellitus (MONDO:0005147), clear cell renal cell carcinoma (MONDO:0005005)

## Full-text entities

- **Genes:** PIGH (phosphatidylinositol glycan anchor biosynthesis class H) [NCBI Gene 100151845], KIF21A (kinesin family member 21A) [NCBI Gene 100520674], MIF (macrophage migration inhibitory factor) [NCBI Gene 397412], RPS6KA2 (ribosomal protein S6 kinase A2) [NCBI Gene 100515286]
- **Diseases:** T1DM (MESH:D003922), autoimmune disease (MESH:D001327), ccRCC (MESH:D002292)

## Figures

10 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11911197/full.md

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Source: https://tomesphere.com/paper/PMC11911197