Reduced PLCG1 expression is associated with inferior survival for myelodysplastic syndromes

Autor: Naoki Mori, Yan-Hua Wang, Masayuki Shiseki, Junji Tanaka, Kentaro Yoshinaga, Satoko Osanai, Mayuko Ishii, Mari Miyazaki
Rok vydání: 2019
Předmět:
0301 basic medicine
Oncology
Adult
Male
Cancer Research
medicine.medical_specialty
lcsh:RC254-282
del(20q)
03 medical and health sciences
Young Adult
PLCG1
0302 clinical medicine
Bone Marrow
Internal medicine
medicine
Biomarkers
Tumor
MDS
Humans
Radiology
Nuclear Medicine and imaging
Clinical significance
Aged
Original Research
Aged
80 and over
Phospholipase C
business.industry
Phospholipase C gamma
Myelodysplastic syndromes
Hazard ratio
Clinical Cancer Research
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
Prognosis
haploinsufficiency
Survival Rate
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Case-Control Studies
Myelodysplastic Syndromes
common deleted region
Female
Bone marrow
Chromosome 20
Haploinsufficiency
business
Follow-Up Studies
Zdroj: Cancer Medicine
Cancer Medicine, Vol 9, Iss 2, Pp 460-468 (2020)
ISSN: 2045-7634
Popis: 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.
We found that reduced PLCG1 expression was associated with worse clinical outcomes, and the level of PLCG1 expression at the time of MDS diagnosis was a useful prognostic marker.
Databáze: OpenAIRE
Externí odkaz: