Clinical Significance of Expression Changes and Promoter Methylation of PLA2R1 in Tissues of Breast Cancer Patients

Abstract

Phospholipase A2 receptor 1 (PLA2R1) expression and its role in the initiation and progression of breast cancer are an unresolved issue. PLA2R1 was found to endorse several tumor suppressive responses, including cellular senescence and apoptosis. Previous in vitro studies demonstrated that DNA hypermethylation was highly associated with the epigenetic silencing of PLA2R1 in breast cancer cell lines. Our objective was to study the level of PLA2R1 mRNA expression and the methylation of its promoter in different histological grades and molecular subtypes of breast cancer. We performed bioinformatics analyses on available human breast cancer expression datasets to assess the PLA2R1 mRNA expression. We used qRT-PCR to evaluate the PLA2R1 mRNA expression and its promoter’s methylation in breast cancer tissue in comparison to breast fibroadenomas. Our results describe, for the first time, the expression of PLA2R1 and the methylation of its promoter in human breast cancer tissues. A significant downregulation of PLA2R1, together with hypermethylation of the promoter was detected in breast cancers of different histological grades and molecular subtypes when compared to benign breast tissues. PLA2R1 promoter hypermethylation was associated with aggressive subtypes of breast cancer. In conclusion, PLA2R1 promoter hypermethylation is a potentially useful diagnostic and prognostic biomarker and could serve as a possible therapeutic target in breast cancer.

Transcriptomic Analysis of Breast Cancer Patients Sensitive and Resistant to Chemotherapy: Looking for Overall Survival and Drug Resistance Biomarkers

“… 57 In breast cancer, negative regulation of this gene was reported in all molecular subtypes, and promoter hypermethylation of this gene has been associated with aggressive subtypes. 58 Regarding its role in chemotherapy, PLA2R1 regulates JAK/STAT signaling, and the targeting of PLA2R1 overcomes senescence. 59 All these reports indicate that this gene could play an important role in the resistance and OS.…”

Transcriptomic analysis of breast cancer patients sensitive and resistant to chemotherapy: Looking for overall survival and drug resistance biomarkers

“…The knockdown of this gene in prostate cancer cells increases cell proliferation but does not affect their sensitivity to docetaxel 47 . In breast cancer, negative regulation of this gene was reported in all molecular subtypes and promoter hypermethylation of this gene has been associated with aggressive subtypes 48 . Regarding its role in chemotherapy, PLA2R1 regulates JAK/STAT signaling and the targeting of PLA2R1 overcomes senescence 49 .…”

Comprehensive analysis of tissue proteomics in patients with papillary thyroid microcarcinoma uncovers the underlying mechanism of lymph node metastasis and its significant sex disparities

“…Functional experiments have demonstrated that PLA2R1 controls cancer cell death by influencing mitochondrial biology. Previous studies have also demonstrated that the downregulation of PLA2R1 is related to thyroid, breast, and kidney cancers (37,38). Mitochondrial amidoxime reducing component 1 (MTARC1) is a nitric oxide synthase attached to the mitochondrial membrane that is associated with increased antioxidant capacity, which can be considered the response to counteract augmented oxidative stress (39).…”