Dataset Information

Identification of CDKN3 as an independent prognostic marker in LGG correlates with tumor proliferation and immune infiltration

ABSTRACT: Low-grade glioma (LGG) is a primary, slow-growing brain tumor; however, its treatment and prognosis remain challenging. In this study, we analyzed cancer data from the TCGA database, focusing particularly on the expression of the CDKN3 gene in LGG. The results showed that high CDKN3 expression in LGG patients was significantly associated with poor survival outcomes. Further gene expression analysis revealed that 379 genes were significantly upregulated in LGG samples with high CDKN3 expression, and these genes were primarily involved in the mitotic cell cycle and extracellular matrix organization. Additionally, high CDKN3 expression was closely linked to key signaling pathways such as tumor inflammation, hypoxic response, and tumor proliferation. Immune microenvironment analysis showed that high CDKN3 expression significantly increased the expression of CD4+ T cells and specific immune checkpoint genes, suggesting a potentially poor response to immune checkpoint blockade therapy. Through in vitro and in vivo experiments, we confirmed that CDKN3 silencing significantly inhibited the proliferative capacity of LGG cells. Proteomics revealed that CDKN3 can bind ARG1 and upregulate intracellular arginine concentrations. These findings not only improve our understanding of LGG biology but also provide scientific evidence for developing potential therapeutic strategies targeting CDKN3.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain, Macroglial Cell

DISEASE(S): Brain Cancer

SUBMITTER: pu wang

LAB HEAD: pu wang

PROVIDER: PXD052180 | Pride | 2024-05-10

REPOSITORIES: Pride

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			Action	DRS
	CON.raw	Raw
	FAST.fasta	Fasta
	proteins.xlsx	Xlsx

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Publications

Identification of KIFC1 as an independent prognostic marker in renal clear cell carcinoma correlates with tumor proliferation and immune infiltration.

Du Bin B Wang Jia J Zheng Jinping J Huo Jing J Wang Pu P

Scientific reports 20231003 1

Renal clear cell carcinoma (ccRCC) is the world's most common form of cancer. Up to a third will develop metastases; the 5-year survival rate of the patients was only 14%. Practical prognostic markers remain to be discovered. Kinesin-like protein (KIFC1), a critical factor in maintaining the stability of the microtubule system, has significant prognostic value in some tumors. We analyzed the prognostic value, associated signaling pathways, and regulatory mechanisms of KIFC1 in ccRCC through bioi ...[more]

PMID: 37789080

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Project description:Low grade gliomas (LGG) account for about two-thirds of all glioma diagnoses in adolescents and young adults (AYA) and malignant progression of these patients leads to dismal outcomes. Recent studies have shown the importance of the dynamic tumor microenvironment in high-grade gliomas (HGG), yet its role is still poorly understood in low-grade glioma malignant progression. Here, we investigated the heterogeneity of the immune microenvironment using a platelet-derived growth factor (PDGF)-driven RCAS (replication-competent ASLV long terminal repeat with a splice acceptor) glioma model that recapitulates the malignant progression of low to high-grade glioma in humans and also provides a model system to characterize immune cell trafficking and evolution. To illuminate changes in the immune cell landscape during tumor progression, we performed single-cell RNA sequencing on immune cells isolated from animals bearing no tumor (NT), LGG and HGG, with a particular focus on the myeloid cell compartment, which is known to mediate glioma immunosuppression. LGGs demonstrated significantly increased infiltrating T cells, CD4 T cells, CD8 T cells, B cells, and natural killer cells in the tumor microenvironment, whereas HGGs significantly abrogated this infiltration. Our study identified two distinct macrophage clusters in the tumor microenvironment; one cluster appeared to be bone marrow-derived while another was defined by overexpression of Trem2, a known anti-tumor immunity marker in myeloid cell subpopulations. Our data demonstrates that these two distinct macrophage clusters show an immune-activated phenotype (Stat1, Tnf, Cxcl9 and Cxcl10) in LGG which evolves to an immunosuppressive state (Lgals3, Apoc1 and Id2) in HGG that restricts T cell recruitment and activation. We identified CD74 and macrophage migration inhibition factor (MIF) as potential targets for these distinct macrophage populations. Interestingly, these results were mirrored by our analysis of the TCGA dataset, which demonstrated a statistically significant association between CD74 overexpression and decreased overall survival in AYA patients with grade II LGGs. Targeting immunosuppressive myeloid cells and intra-tumoral macrophages within this therapeutic window may ameliorate mechanisms associated with immunosuppression before and during malignant progression.