Expression of STK15, CENPW and TIMP1 genes in breast and colorectal cancers from human blood samples

Cancer is one of the highest incidence and mortality worldwide. Despite the great information on cancer, particularly in breast cancer (BC) and colorectal cancer (CRC), the rate of BC and CRC incidence and deaths remains alarming. This pilot case-control study is conducted to further understand the...

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Main Author:	Goh, Lucky Poh Wah
Format:	Thesis
Language:	English English
Published:	2015
Subjects:	QH426-470 Genetics
Online Access:	https://eprints.ums.edu.my/id/eprint/39461/1/24%20PAGES.pdf https://eprints.ums.edu.my/id/eprint/39461/2/FULLTEXT.pdf
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spelling	my-ums-ep.394612024-08-09T00:11:58Z Expression of STK15, CENPW and TIMP1 genes in breast and colorectal cancers from human blood samples 2015 Goh, Lucky Poh Wah QH426-470 Genetics Cancer is one of the highest incidence and mortality worldwide. Despite the great information on cancer, particularly in breast cancer (BC) and colorectal cancer (CRC), the rate of BC and CRC incidence and deaths remains alarming. This pilot case-control study is conducted to further understand the biology of cancer especially in mRNA/gene expression aspect using whole blood system by analyzing the differential gene expression of three potential BC and CRC related genes which were STK15, CENPW, and TIMP1. Whole blood samples were collected from 31 healthy individuals and 36 cancer patients (14 BC and 22 CRC) followed by total RNA isolation using Tempus™ Blood RNA System. The RNA integrity number (RIN) of extracted RNA was determined using bioanalyzer. Gene expression analysis was performed with 5’-hydrolysis probes in triplicates using real-time PCR. Additionally, influence of other factors such as age, gender, and gene polymorphism to gene expression were also evaluated in this study. Statistical Mann-Whitney U-test was applied to determine the differential expressions of STK15, CENPW and TIMP1 normalized to two reference genes (GAPDH and HPRT1) in BC and CRC patients, with p<0.05 as statistical significant. This study showed that the extracted total RNA was highly intact with RIN>7.0 for reliable gene expression analysis. STK15 expression was significantly (p<0.05) downregulated in CRC regardless of both age and gender. Interestingly, a significant (p<0.05) reduction of STK15 expression of BC were found in age ≥50 but not in age <50 suggesting an age related factor in BC and not in CRC. No significant difference was observed in the downregulation of CENPW and TIMP1 gene expression in BC and CRC. Further investigation based on genotyping of the STK15 Phe31Ile polymorphism showed that STK15 expression in BC was non-significantly (p>0.05) downregulated after samples were grouped according to genotypes (Phe/Phe, Phe/Ile, and Ile/Ile), but significant (p<0.05) downregulation was observed in CRC patients carrying homozygous wild-type (Phe/Phe) or homozygous variant (Ile/Ile) genotypes. This indicated Phe/Phe or Ile/Ile genotype in STK15 Phe31Ile polymorphism associated to reduce STK15 expression in CRC but not in BC. In summary, the reduced STK15 expressions of this study provide an initial insight of using blood-based biomarker for BC and CRC. 2015 Thesis https://eprints.ums.edu.my/id/eprint/39461/ https://eprints.ums.edu.my/id/eprint/39461/1/24%20PAGES.pdf text en public https://eprints.ums.edu.my/id/eprint/39461/2/FULLTEXT.pdf text en validuser masters Universiti Malaysia Sabah Fakulti Sains dan Sumber Alam
institution	Universiti Malaysia Sabah
collection	UMS Institutional Repository
language	English English
topic	QH426-470 Genetics
spellingShingle	QH426-470 Genetics Goh, Lucky Poh Wah Expression of STK15, CENPW and TIMP1 genes in breast and colorectal cancers from human blood samples
description	Cancer is one of the highest incidence and mortality worldwide. Despite the great information on cancer, particularly in breast cancer (BC) and colorectal cancer (CRC), the rate of BC and CRC incidence and deaths remains alarming. This pilot case-control study is conducted to further understand the biology of cancer especially in mRNA/gene expression aspect using whole blood system by analyzing the differential gene expression of three potential BC and CRC related genes which were STK15, CENPW, and TIMP1. Whole blood samples were collected from 31 healthy individuals and 36 cancer patients (14 BC and 22 CRC) followed by total RNA isolation using Tempus™ Blood RNA System. The RNA integrity number (RIN) of extracted RNA was determined using bioanalyzer. Gene expression analysis was performed with 5’-hydrolysis probes in triplicates using real-time PCR. Additionally, influence of other factors such as age, gender, and gene polymorphism to gene expression were also evaluated in this study. Statistical Mann-Whitney U-test was applied to determine the differential expressions of STK15, CENPW and TIMP1 normalized to two reference genes (GAPDH and HPRT1) in BC and CRC patients, with p<0.05 as statistical significant. This study showed that the extracted total RNA was highly intact with RIN>7.0 for reliable gene expression analysis. STK15 expression was significantly (p<0.05) downregulated in CRC regardless of both age and gender. Interestingly, a significant (p<0.05) reduction of STK15 expression of BC were found in age ≥50 but not in age <50 suggesting an age related factor in BC and not in CRC. No significant difference was observed in the downregulation of CENPW and TIMP1 gene expression in BC and CRC. Further investigation based on genotyping of the STK15 Phe31Ile polymorphism showed that STK15 expression in BC was non-significantly (p>0.05) downregulated after samples were grouped according to genotypes (Phe/Phe, Phe/Ile, and Ile/Ile), but significant (p<0.05) downregulation was observed in CRC patients carrying homozygous wild-type (Phe/Phe) or homozygous variant (Ile/Ile) genotypes. This indicated Phe/Phe or Ile/Ile genotype in STK15 Phe31Ile polymorphism associated to reduce STK15 expression in CRC but not in BC. In summary, the reduced STK15 expressions of this study provide an initial insight of using blood-based biomarker for BC and CRC.
format	Thesis
qualification_level	Master's degree
author	Goh, Lucky Poh Wah
author_facet	Goh, Lucky Poh Wah
author_sort	Goh, Lucky Poh Wah
title	Expression of STK15, CENPW and TIMP1 genes in breast and colorectal cancers from human blood samples
title_short	Expression of STK15, CENPW and TIMP1 genes in breast and colorectal cancers from human blood samples
title_full	Expression of STK15, CENPW and TIMP1 genes in breast and colorectal cancers from human blood samples
title_fullStr	Expression of STK15, CENPW and TIMP1 genes in breast and colorectal cancers from human blood samples
title_full_unstemmed	Expression of STK15, CENPW and TIMP1 genes in breast and colorectal cancers from human blood samples
title_sort	expression of stk15, cenpw and timp1 genes in breast and colorectal cancers from human blood samples
granting_institution	Universiti Malaysia Sabah
granting_department	Fakulti Sains dan Sumber Alam
publishDate	2015
url	https://eprints.ums.edu.my/id/eprint/39461/1/24%20PAGES.pdf https://eprints.ums.edu.my/id/eprint/39461/2/FULLTEXT.pdf
_version_	1811770513766219776

Expression of STK15, CENPW and TIMP1 genes in breast and colorectal cancers from human blood samples

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