Cluster of Differentiation 44 (CD44) Gene Variants: A Putative Cancer Stem Cell Marker in Risk Prediction of Bladder Cancer in North Indian Population

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• 作者：Archana Verma ; Rakesh Kapoor ; Rama Devi Mittal
• 关键词：BC ; CD44 ; MIBC ; NMIBC ; BCG immunotherapy
• 刊名：Indian Journal of Clinical Biochemistry
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：32
• 期：1
• 页码：74-83
• 全文大小：
• 刊物主题：Biochemistry, general; Microbiology; Chemistry/Food Science, general; Pathology;
• 出版者：Springer India
• ISSN：0974-0422
• 卷排序：32

文摘

CD44 is involved in cancer-cell growth, invasion, proliferation and metastasis and is also a causal factor for acquisition of resistance to apoptosis. Therefore we evaluated different SNPs of CD44 gene viz. CD44rs187116 A/G, CD44rs4755392 A/T, CD44rs187115 C/T, CD44rs13347 C/T and CD44 rs353639 G/T for bladder cancer risk in North Indian population. 240 bladder cancer patients and 270 cancer free controls were recruited in this study. Genotyping was done by PCR–RFLP for CD44rs187116 A/G. However, CD44rs4755392 A/T, CD44rs187115 C/T, CD44rs13347 C/T and CD44 rs353639 G/T were genotyped by allelic discrimination Taqman® assay. Statistical analysis was done by SPSS. In-silico analysis was done using F-SNP. We found reduced risk in variant genotype, TT of rs4755392 (p = 0.011) as well as in variant allele, T (p = 0.045). No risk was seen in rs13347, heterozygous genotype, CT (p = 0.023) and variant allele, T (p = 0.007). The dominant model, CT + TT also revealed reduced risk (p = 0.009). A marginal risk was seen in dominant model, GT + TT of rs353639 (p = 0.044) and reduced risk in variant allele T (p = 0.040). A significant manifold risk was seen in smokers carrying variant genotype, TT of CD44rs353639 G/T (p = 0.038, OR 1.960). Haplotypic analysis revealed significant association in 4 sets viz. TCCGG p = 0.005, TTCGA p = 0.039, ACTGG p = 0.008 and TCTGA p = 0.006. In-silico analysis using F-SNP, showed altered transcriptional regulation for rs187115, rs13347 and rs353639. Our study suggests that rs353639 shows a marginal risk for bladder cancer susceptibility, whereas rs4755392 and rs13347 have reduced risk of bladder cancer and rs187115 and rs187116 had no effect on bladder cancer susceptibility in North Indians.