Expression patterns and the prognostic value of the SMYD family members in human breast carcinoma using integrative bioinformatics analysis

Abstract

Suppressor of variegation, Enhancer of Zeste, Trithorax and Myeloid-Nervy-DEAF1 domain-containing (SMYD) proteins are a set of lysine methyltransferases involved in a range of diverse biological functions, including gene expression, and regulation of skeletal and cardiac-muscle development. These proteins may additionally serve roles in a number of different types of cancer. However, the roles of the five SMYD proteins, SMYD 1/2/3/4/5, their expression patterns and prognostic value remain unclear. In the present study, the transcriptional expression levels of the five SMYD proteins were compared with the survival data of patients with breast carcinoma (BC) from the ONCOMINE dataset, Breast Cancer Gene-Expression Miner v4.0, Kaplan-Meier Plotter, The Cancer Genome Atlas and cBioPortal. An increase in the SMYD2/3/5 mRNA expression levels and a decrease in SMYD1/4 mRNA expression levels in BC tissues compared with normal tissues were identified. Increased SMYD3 mRNA and decreased SMYD5 mRNA expression levels were associated with decreased levels of histological differentiation, according to the Scarff-Bloom-Richardson grading system. Kaplan-Meier curves demonstrated that the increased SMYD1/4 and decreased SMYD2/3 mRNA expression levels were associated with good relapse-free survival (RFS) in patients with BC. Furthermore, SMYD2 mRNA expression levels were associated with the RFS of patients with BC with metastatic relapse, and SMYD4 may serve as a tumor suppressor in patients with BC, as patients with increased SMYD4 mRNA expression levels had significantly better RFS compared with decreased SMYD4 mRNA expression levels. The present data suggested that SMYD2 and SMYD3 may be potential biomarkers for diagnosis of BC. Additionally, SMYD2 and SMYD4 may be potential prognostic indicators of patients with BC.

Validation of Novel Prognostic Biomarkers for Early-Stage Clear-Cell, Endometrioid and Mucinous Ovarian Carcinomas Using Immunohistochemistry

“…SETD3-positivity has been reported to be associated with poor prognosis in hepatocellular carcinoma (32). Similar to our expression profile, high levels of SMYD2 expression has been associated with unfavorable prognosis in different cancer types, such as breast cancer (mRNA expression) and cervical cancer (protein expression) (33,34). A recent study reported overexpression of SMYD2 in cancer vs. normal tissue, and associated higher expression of SMYD2 with enhanced proliferation in HGSC (35).…”

Protein Deimination and Extracellular Vesicle Profiles in Antarctic Seabirds

“…It belongs to the Smyd Family of Methyltransferases, which is recognized in diverse taxa [211]. SMYD can methylate histones and non-histone proteins and have diverse roles in chromatin remodelling as well as normal development, in cell growth and differentiation and in the regulation of a series of pathophysiological processes, including cardiac and skeletal muscle physiology and pathology and cancer [212][213][214]. As PADs cause deimination of several histones, the deimination of histone regulatory proteins, such as SMYD here, may be of considerable interest, particularly in the light of their multifaceted functions in regulating a range of histone and non-histone proteins, including histone H3 in Gallus gallus [16].…”

Genomic profiling of newly diagnosed glioblastoma patients and its potential for clinical utility – a prospective, translational study

“…This potential prognostic mutation has not been reported previously and should be evaluated in future studies. The functional GRB2 protein acts as a negative regulator of the RAS pathway by inhibiting EGFRs [32], and SMYD4 is involved in inhibition of gene expression and has been suggested as a tumor suppressor gene [33,34]. In 4/6 patients with GRB2 alterations, alterations in SMYD4 were also present.…”