SPP1, a potential diagnostic marker that correlated with immune infiltration in right heart failure

Background: Right ventricle failure (RVF) is a clinical syndrome with high mortality that is frequently secondary to cardiovascular and pulmonary vascular diseases. There is growing evidence that the outcome of RVF is closely related to the immune response. This study is to explore SPP1 as a potential diagnostic marker related to the infiltration of immune cells in RVF. Methods: The gene expression profile of GSE161473 was downloaded from Gene Expression Omnibus and analyzed by R. Protein-protein interaction (PPI) networks which were established with STRING. Gene Ontology and KEGG enrichment analysis were performed using R-package “Clusterprofiler.” Differentially expressed immune-related genes (DEIRG) were identified using ImmPort. The infiltration of immune cells in RVF was evaluated using CIBERSORT, and the correlation between key hub genes and immune cells was analyzed by R. Rats model of RVF which was established by monocrotaline (MCT) (60 mg/kg, IP). The immune status and differentially expressed immune-related genes (IRGs) in the right heart tissue of rats with RVF in PAH were verified by immunofluorescence, immunohistochemistry, Real-time PCR, and western blotting. In addition, the serum of right heart-failing patients was used to verify the possibility of SPP1 as a biomarker. Result: A total of 107 differentially expressed genes (DEGs) were screened, from which 20 DEIRGs were screened by ImmPort, PPI, and functional enrichment analysis. 4 Hub genes (ADM, FGF12, AREG and SPP1) were confirmed by RT-PCR. In addition, SPP1 was identified as the most potent biomarker. ImmuCellAI immune infiltration analysis showed that a higher proportion of monocytes, M2 macrophages, memory B cells, resting NK cells, and resting mast cells were elavated in the RVF group. Finally, SPP1 was positively correlated with monocytes and M2 macrophages and negatively correlated with memory B cells and CD8 + T cells. Conclusion: A variety of immune cells such as monocytes, macrophages, T cells, B cells, and mast cells are involved in the development of RVF. Dysregulated immune responses were found in the right cardiac tissue of patients with RVF. SPP1 was considered a key hub gene to discriminate between RVF and normal groups. Parts of IRGs, especially SPP1, may be used as biomarkers to assist in the diagnosis and evaluation of RVF. This work was supported by the Shandong Provincial Natural Science Foundation of China (ZR2022MH052), China Postdoctoral Science Foundation (No. 2021M691944) to Xiaomei Yang. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.