Methylation status and protein expression of RASSF1A in breast cancer patients

Abstract

Recently genetics and epigenetics alterations have been found to be characteristic of malignancy and hence can be used as targets for detection of neoplasia. RAS association domain family protein 1A (RASSF1A) gene hypermethylation has been a subject of interest in recent researches on cancer breast patients. The aim of the present study was to evaluate whether RASSF1A methylation status and RASSF1A protein expression are associated with the major clinico-pathological parameters. One hundred and twenty breast cancer Egyptian patients and 100-control subjects diagnosed with benign lesions of the breast were enrolled in this study. We evaluated RASSF1A methylation status in tissue and serum samples using Methyl specific PCR together with RASSF1A protein expression in tissues by immunohistochemistry. Results were studied in relation to known prognostic clinicopathological features in breast cancer. Frequency of RASSF1A methylation in tissues and serum were 70 and 63.3 % respectively and RASSF1A protein expression showed frequency of 46.7 %. There was an association between RASSF1A methylation in tissues, serum and loss of protein expression in tissues with invasive carcinoma, advanced stage breast cancer, L.N. metastasis, ER/PR and HER2 negativity. RASSF1A methylation in serum showed high degree of concordance with methylation in tissues (Kappa = 0.851, P < 0.001). RASSF1A hypermethylation in tissues and serum and its protein expression may be a valid, reliable and sensitive tool for detection and follow up of breast cancer patients.

The Hippo pathway in colorectal cancer

“…Phosphorylation β loss of function in prostate cancer [119], CCL: overexpression inhibits cell proliferation and promote apoptosis in HepG2 cells [87] Mouse double KO: cholangiocarcinoma [46,101], HCC [120] Decreased mRNA level in tumour associated with node metastasis [121], mouse double KO: crypt dysplasia, colon adenoma [46,78,120] RASSF1, RASSF1A TSG: promoter hypermethylation and decrease expression in cancer: thyroid [122], oesophageal [123], prostate [124], colorectal, breast [125] TSG; promoter hypermethylation and decrease expression in CRC [126,127] SAV1, Salvador TSG: LOH and downregulation in renal cell carcinoma [128], no gene mutation in stomach, liver and lung cancer [129] CCL: overexpression induces apoptosis in MCF-7 cells [130] No gene mutation in CRC [129] LATS1 TSG: decrease expression in cancer: glioma [131], NSLC [132], sarcoma [133] and astrocytoma [134]. CCL: LATS1 degradation inhibits apoptosis in MCF10A cells [135] TSG: promoter hypermethylation and mRNA decrease in CRC [86] LATS2 TSG: decrease expression in: malignant mesothelioma (and LOH) [136], NSLC (no mutation found) [137] and astrocytoma [134] OG: overexpression in AML [138], nosopharyngeal carcinoma [139] TSG: downregulation in CRC [87] …”

Relationship between RAS Association Domain Family Protein 1A Promoter Methylation and the Clinicopathological Characteristics in Patients with Ovarian Cancer: A Systematic Meta-Analysis

“…Tumor-suppressor genes methylation of the promoter regions within the CpG islands leads to the downregulation or loss of gene expression [47, 48]. The dysfunction of the RASSF1A gene associated with promoter methylation has been shown in several types of human cancers, such as adrenocortical carcinoma [49], breast cancer [50], nasopharyngeal carcinoma [51], and ovarian cancer [35]. The RASSF1A promoter is found to be commonly methylated in ovarian carcinoma [22, 31, 32, 39].…”

TES was epigenetically silenced and suppressed the epithelial–mesenchymal transition in breast cancer

“…In human cancer, a great many tumor suppressor genes were silenced by promoter hypermethylation and lost their anticancer functions [28]. In breast cancer, hypermethylation of RASSF1A, DAPK, p21, and RUNX3 were the most reported and might play important roles during tumorigenesis and progression [29][30][31][32].…”