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. 2025;25(2):159-169.
doi: 10.2174/0115680096307100240801095132.

PLCG2, A Regulator of Lung Adenocarcinoma Proliferation and Migration Associated with Immune Infiltration

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PLCG2, A Regulator of Lung Adenocarcinoma Proliferation and Migration Associated with Immune Infiltration

Shuhui Chen et al. Curr Cancer Drug Targets. 2025.

Abstract

Background: Results from the TCGA database showed that phosphatidylinositolspecific phospholipase Cγ2 (PLCG2) expression level in Lung Adenocarcinoma (LUAD) was notably decreased compared to adjacent tissues, so we unveiled its role of LUAD.

Objective: This study aims to explore the expression and clinical significance of Phosphatidylinositol- specific phospholipase Cγ2 (PLCG2) in lung adenocarcinoma (LUAD) cells and its role in cell proliferation and metastasis.

Methods: Differential PLCG2 mRNA and protein levels between LUAD tissues and adjacent tissues were analyzed from the TCGA database, TIMER, and UALCAN database. Differentially expressed genes were screened for patients in the high and low PLCG2 mRNA expression groups by the R package as well as GSEA. The expression level of PLCG2 in LUAD cells was detected using qRT-PCR and CCK8, clone formation, Transwell, and Western blot assays.

Results: PLCG2 was lowly expressed in LUAD and did not significantly correlate with the prognosis of LUAD. PLCG2 expression levels varied significantly in terms of patients' gender, age, T, N, and pathological stage. GO/KEGG enrichment analysis showed that co-expression of PLCG2 was mainly associated with the immune response- regulating cell-surface receptors, and so on. GSEA analysis showed enrichment pathways of PLCG2-related differential gees were primarily associated with the olfactory transduction pathway, ribosome, etc. R software analysis revealed a significant correlation between PLCG2 expression and six types of immune-infiltrating cells, positively correlated with immune checkpoint-related genes and negatively regulated by tumor mutational load. Overexpressing PLCG2 showed reduced LUAD cell proliferation, clone formation, cell migration and invasion, and epithelial-mesenchymal transition-associated proteins, compared with the control group.

Conclusion: PLCG2 is lowly expressed in LUAD tissues and is involved in immune infiltration of LUAD, inhibiting LUAD cell proliferation and metastasis.

Keywords: Lung adenocarcinoma; PLCG2; immune infiltration; lung cancer.; metastasis; migration; proliferation; tumor-infiltration immune cells.

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