Study on the SFRP4 gene polymorphism and expression in prostate cancer
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Ó Indian Academy of Sciences (0123456789().,-volV) (0123456789().,-volV)
RESEARCH NOTE
Study on the SFRP4 gene polymorphism and expression in prostate cancer AISHWARYA NATARAJAN, SHAILE SUDHA BANDLA, MOHAN DAMODARAN, SANDHYA SUNDARAM and VETTRISELVI VENKATESAN* Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai 600 116, India *For correspondence. E-mail: [email protected]. Received 7 October 2019; revised 24 August 2020; accepted 24 August 2020 Abstract. Prostate cancer is a heterogeneous disease and considered to be the most commonly diagnosed cancer. SFRP4 gene acts as Wnt antagonist in the Wnt signalling pathway, thereby playing an important role in carcinogenesis. The aim of the present study was to investigate two single-nucleotide polymorphisms: c.958 C[A (rs1802073) and c.1019 G[A (rs1802074) in the SFRP4 gene and its expression in prostate cancer. A sample size of 100 cases and 100 age-matched controls were recruited for the study. Statistical analysis revealed the heterozygous GA genotype of rs1802074 significantly increased in cases when compared to controls. Analysis of sFRP4 expression based on the genotypes showed a significantly increased expression for the heterozygous GA and homozygous AA genotypes in cases when compared to the controls. Fold change was calculated using 2-DDCT method and the results showed that there were a 3.4 and 4.5 fold increase in the sFRP4 expression for GA and AA genotypes, respectively. Our results suggest that the rs1802074 polymorphism in SFRP4 gene may be associated with the risk of prostate cancer. Keywords.
secreted frizzled related protein 4; prostate cancer; genotyping; haplotypes.
Introduction Prostate cancer, referred to as malignancy of elderly people, is the second most common type of cancer among men and ranks fifth in cancer mortality rate worldwide (Banerjee and Kaviani 2016). The aetiology and pathological mechanism of prostate cancer remains unclear. Many signalling pathways are involved in the growth and progression of prostate cancer, of which the Wnt signalling pathway plays a pivotal role. WNTs are a family of 19 secreted glycoproteins that are of prime importance in both the developing foetus and adults (Anastas and Moon 2013). Wnt signalling pathway plays a very crucial role in various biological processes including embryonic development, cell proliferation, cell fate specification and tissue homeostasis (Shi et al. 2007). There is abnormal activation of the Wnt signalling pathway in prostate cancer, and hence, the expression of Wnt ligands is altered (Kypta and Waxman 2012). Secreted frizzled related proteins (sFRPs), containing five family members (1–5), are secreted glycoproteins that are commonly referred to as ‘Wnt antagonists’ (Surana et al.
2014). Studies have revealed that the sFRPs are transcriptionally inactivated in many tumours and possibly acts as a tumour suppressor gene (Rubin et al. 2006). The SFRP4 gene located on chromosome 7 (7p14.1) is considered to be the largest member of the family and is s
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