# SPP1 May Play an Important Role in the Carcinoid Nature of PAH

**Authors:** Yuxia Huang, Sheng Yan, Jing Zhu, Wentian Zhang

PMC · DOI: 10.1155/mi/7457106 · Mediators of Inflammation · 2025-12-05

## TL;DR

This study explores how SPP1, a gene linked to RNA modification, may contribute to the cancer-like features of pulmonary arterial hypertension (PAH) by comparing it with non-small cell lung cancer.

## Contribution

The study identifies SPP1 as a key gene in PAH's cancer-like behavior through m7G modification and immune cell infiltration analysis.

## Key findings

- SPP1 and CD163 are m7G-related genes that are differentially expressed in PAH and NSCLC.
- SPP1 is significantly correlated with macrophage and mast cell infiltration in NSCLC.
- Higher SPP1 and CD163 expression is linked to poor prognosis in NSCLC and PAH progression in rat models.

## Abstract

Pulmonary arterial hypertension (PAH) was a cancer‐like disease. It shared several mechanisms, including perivascular inflammation. But the genes common and different between cancer and PAH was still unclear. We aimed to analyze the genes common in the two diseases, especially the N7‐methylguanosine (m7G) genes.

We acquired dataset GSE1519, GSE113439, and GSE81089 and recognized differentially expressed genes (DEGs) and investigated their functions utilizing R software. m7G‐related genes were identified using a online tool RMvar. The extent of immune cell infiltration in the normal and PAH tissues, nonsmall cell lung cancer (NSCLC) tissues was determined using ImmuneCellAI and CIBERSORT. Additionally, the association between diagnostic markers and immune cells was analyzed. Single cell analysis and Cellchat were used to analyze the role of SPP1 in the PAH.

Among five DEGs overlapped by the differently datasets about NSCLC, CD163, and SPP1 were m7G genes. The immune cell infiltration results suggested that PAH and NSCLC shared different immune cell infiltration. SPP1 was significantly correlated to the macrophage cells and activated mast cells in NSCLC. Higher expression of CD163 and SPP1 might be related to the progression of monocrotaline (MCT) induced rats in the dataset GSE229361. The KM survival analysis suggested that higher expression of CD163 and SPP1 related to poor prognosis of NSCLC. The important role of SPP1 in PAH was verified using single cell anslysis.

Different T cells infiltration contributed to the development of PAH and NSCLC. SPP1 might be vital for the cancer‐like characteristics of PAH.

## Linked entities

- **Genes:** SPP1 (secreted phosphoprotein 1) [NCBI Gene 6696], CD163 (CD163 molecule) [NCBI Gene 9332]
- **Chemicals:** monocrotaline (PubChem CID 9415)
- **Diseases:** pulmonary arterial hypertension (MONDO:0015924), non-small cell lung cancer (MONDO:0005233)

## Full-text entities

- **Genes:** Cd163 (CD163 molecule) [NCBI Gene 312701] {aka ED2}, Spp1 (secreted phosphoprotein 1) [NCBI Gene 25353] {aka OSP}
- **Diseases:** cancer (MESH:D009369), NSCLC (MESH:D002289), inflammation (MESH:D007249), PAH (MESH:D000081029)
- **Chemicals:** MCT (MESH:D016686)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

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## References

37 references — full list in the complete paper: https://tomesphere.com/paper/PMC12767451/full.md

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Source: https://tomesphere.com/paper/PMC12767451