Reduced PLCG1 expression is associated with inferior survival for myelodysplastic syndromes

Abstract

The PLCG1 gene, which encodes the phospholipase C γ1 isoform, is located within the commonly deleted region of the long arm of chromosome 20 (del(20q)) observed in myelodysplastic syndromes (MDS). Phospholipase C is involved in diverse physiological and pathological cellular processes through inositide signaling. We hypothesized that reduced PLCG1 expression because of haploinsufficiency by del(20q) plays a role in the molecular pathogenesis of MDS. Therefore, we analyzed PLCG1 expression in bone marrow mononuclear cells at diagnosis in 116 MDS patients with or without del(20q) by quantitative RT‐PCR to evaluate its clinical significance. The expression level of PLCG1 was significantly lower not only in MDS patients with del(20q) but also in those without del(20q) compared to that of the controls, which suggests that reduced PLCG1 expression is a common molecular event in MDS. Patients in the lowest quartile (Q4) group for PLCG1 expression had lower overall survival (OS) compared to that of other patients (Q1‐Q3) (log‐rank test, P = .0004) with estimated median OS times of 22 in the Q4 group and 106 months in the Q1‐3 group. Univariate and multivariate analysis indicated reduced PLCG1 expression (Q4) was associated with lower OS (hazard ratio 2.58, 95% CI 1.35‐4.84, P = .0049), which suggests that reduced PLCG1 expression is an independent prognostic factor for OS. In addition, patients were well‐stratified for OS by combining PLCG1 expression level (Q4 vs Q1‐3) and bone marrow blast percentage (5% or more vs less than 5%). Thus, the level of PLCG1 expression at time of diagnosis is a prognostic biomarker for MDS.

Identification of the Pyroptosis-Related Prognosis Gene Signature and Immune Infiltration in Hepatocellular Carcinoma

“…Knockdown of PLCG1 may interrupt the GSDMD mediated pyroptosis [ 21 ]. The PLCG1 expression could also be a biomarker for myelodysplastic syndromes and oral squamous cell carcinoma [ 22 , 23 ]. The dysregulated PLCG1 in HCC tissues and cell lines was also proved [ 8 ].…”

Construction of a metabolism-related gene prognostic model to predict survival of pancreatic cancer patients

“…By activating PLCG1, a novel member of the TSPAN superfamily-tetraspanin 1 may affect PC cell migration and invasion as well as MMP2 expression [ 43 ]. However, in myelodysplastic syndromes, reduced PLCG1 expression is associated with inferior survival [ 44 ]. We therefore speculate that the paradox of the opposing effects of ARG2 and PLCG1 expressions may be due to the specific environmental ways in which these two genes regulate cellular processes through different regulatory networks.…”

Targeting PRKACA inhibits proliferation and sensitizes glioma cells to temozolomide via pyroptosis pathway

“…IL6 is a multipotent cytokine with a wide range of functions, and it has been reported to be a hub gene in a risk model of head and neck squamous cell carcinoma (HNSCC) (27). PLCG1 overexpression is associated with poor survival in lower-grade gliomas and small cell lung cancer(28, 29); however, it has the opposite prognostic effect in myelodysplastic syndromes (30). The pro-in ammatory cytokine TNF-α encoded by TNF functions as a regulator in a wide range of biological processes.…”