SNCA correlates with immune infiltration and serves as a prognostic biomarker in lung adenocarcinoma

Abstract

Background The SNCA gene is a critical gene in Parkinson’s disease (PD) pathology. Accumulating evidence indicates that SNCA is involved in tumorigenesis; however, the role of SNCA in lung adenocarcinoma (LUAD) remains unclear. This study aimed to explore the potential value of SNCA as a prognostic and diagnostic molecular marker in LUAD. Methods In this study, we explored the expression pattern, prognostic value, and promoter methylation status of SNCA in LUAD based on Oncomine, UALCAN, and Kaplan–Meier Plotter. Then, using TIMER, we investigated the correlation between SNCA expression and immune infiltration. And cBioPortal were used to analysis the correlation between SNCA expression and immune checkpoint. The transcriptome data of A549 cells overexpressing SNCA were used to further study the potential immune role of SNCA in LUAD. The effect of SNCA on proliferation of A549 cells were evaluated by CCK-8, EdU and colony formation. Finally, LUAD cell lines treated with 5-aza-dC were used to explore the correlation between increased promoter methylation and downregulated mRNA expression of SNCA. Results In general, the expression level of SNCA in LUAD tissue was lower than that in normal tissue, and high expression of SNCA was related to better prognosis. There were significant positive correlations between SNCA expression and immune infiltrations, including CD8+ T cells, macrophages, neutrophils, dendritic cells, B cells, and CD4+ T cells, and immune checkpoints, suggesting that immune infiltration was one of the reasons for the influence of SNCA on prognosis in LUAD. The transcriptome data of A549 cells overexpressing SNCA were further used to screen the relevant immune-related genes regulated by SNCA. Enrichment analysis confirmed that SNCA participates in the PI3K-AKT signaling pathway and other key tumor signaling pathways and regulates the expression of MAPK3, SRC, PLCG1, and SHC1. Cellular proliferation assay showed that SNCA could inhabit the growth of A549 cells via inhibiting activity of PI3K/AKT/ mTOR pathway. Finally, analysis of the methylation level of SNCA promoter showed that the promoter methylation negatively correlated with mRNA level. The expression of SNCA in LUAD cell lines was significantly upregulated by treatment with 5-aza-dC. Conclusion High methylation of SNCA promoter in LUAD is one of the reasons for the downregulation of SNCA mRNA level. Given that SNCA could inhibit the proliferation of A549 cells and correlates with immune infiltrates, it may serve as a prognostic biomarker in LUAD.

The Parkinson's disease‐associated protein α‐synuclein inhibits hepatoma by exosome delivery

“…20 Moreover, exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrin αVβ5 was linked to liver metastasis, while exosomal integrins α6β4 and α6β1 were associated with lung metastasis. 30 Notably, α-syn was expressed in both the central nervous system 8 and various tumors, [11][12][13][14] and toxic phosphorylation of α-syn at S129 was also detected in melanoma cells and secreted vesicles. 15 Thus, the above results suggested a role of α-syn-containing exosomes in distance communication between PD and peripheral cancer, and it is reasonable to speculate that exosomes from PD patients might deliver α-syn in regulating liver cancer.…”

“…It has been reported that overexpression of α‐syn increased the vulnerability of neurons to dopamine‐induced cell death through excess intracellular reactive oxygen species generation in PD cellular model, 9 and phosphorylation at Ser129 was essential for α‐syn‐induced neurotoxicity in a drosophila model of PD 10 . Notably, α‐syn is widely distributed in peripheral tissue cells such as lung adenocarcinomas, pancreatic ductal adenocarcinomas, colorectal cancers, and bladder cancer 11–14 and toxic phosphorylation of α‐syn at Ser129 is also detected in secreted vesicles from melanoma cells 15 . It is also that α‐syn could inhibit the proliferation of lung adenocarcinoma cells via inhibiting PI3K/AKT/mTOR signaling pathway 11 and bladder cancer cell proliferation by arresting the cell cycle in the S phase via upregulation of p53 expression mediated by DNA damages 14 .…”

“…Notably, α‐syn is widely distributed in peripheral tissue cells such as lung adenocarcinomas, pancreatic ductal adenocarcinomas, colorectal cancers, and bladder cancer 11–14 and toxic phosphorylation of α‐syn at Ser129 is also detected in secreted vesicles from melanoma cells 15 . It is also that α‐syn could inhibit the proliferation of lung adenocarcinoma cells via inhibiting PI3K/AKT/mTOR signaling pathway 11 and bladder cancer cell proliferation by arresting the cell cycle in the S phase via upregulation of p53 expression mediated by DNA damages 14 . These research suggest that neurodegeneration and oncogenesis may share common mechanistic foundations.…”

“…| 1163 detected in secreted vesicles from melanoma cells. 15 It is also that α-syn could inhibit the proliferation of lung adenocarcinoma cells via inhibiting PI3K/AKT/mTOR signaling pathway 11 and bladder cancer cell proliferation by arresting the cell cycle in the S phase via upregulation of p53 expression mediated by DNA damages. 14 These research suggest that neurodegeneration and oncogenesis may share common mechanistic foundations.…”

Correction to: SNCA correlates with immune infiltration and serves as a prognostic biomarker in lung adenocarcinoma

“…Following publication of the original article [ 1 ], the authors identified an error in the order of the figures. The correct order is given below.…”