The expression of FLNA and CLU in PBMCs as a novel screening marker for hepatocellular carcinoma

Abstract Early detection improves survival and increases curative probability in hepatocellular carcinoma (HCC). Peripheral blood mononuclear cells (PBMCs) can provide an inexpensive, less-invasive and highly accurate method. The objective of this study is to find the potential marker for HCC screen...

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Autores principales: Rathasapa Patarat, Shoji Riku, Pattapon Kunadirek, Natthaya Chuaypen, Pisit Tangkijvanich, Apiwat Mutirangura, Charoenchai Puttipanyalears
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:9a12337f182644bfa0b70a760b3981232021-12-02T16:17:27ZThe expression of FLNA and CLU in PBMCs as a novel screening marker for hepatocellular carcinoma10.1038/s41598-021-94330-12045-2322https://doaj.org/article/9a12337f182644bfa0b70a760b3981232021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94330-1https://doaj.org/toc/2045-2322Abstract Early detection improves survival and increases curative probability in hepatocellular carcinoma (HCC). Peripheral blood mononuclear cells (PBMCs) can provide an inexpensive, less-invasive and highly accurate method. The objective of this study is to find the potential marker for HCC screening, utilizing gene expression of the PBMCs. Data from the NCBI GEO database of gene expression in HCC patients and healthy donor's PBMCs was collected. As a result, GSE 49515 and GSE 58208 were found. Using both, a statistical significance test was conducted in each gene expression of each data set which resulted in 187 genes. We randomized three selected genes (FLNA, CAP1, and CLU) from the significant p-value group (p-values < 0.001). Then, a total of 76 healthy donors, 153 HCC, 20 hepatic fibrosis, 20 non-alcoholic fatty liver were collected. Quantitative RT-PCR (qRT-PCR) was performed in cDNA from all blood samples from the qRT-PCR, The Cycle threshold (Ct) value of FLNA, CLU, CAP1 of HCC group (28.47 ± 4.43, 28.01 ± 3.75, 29.64 ± 3.90) were lower than healthy group (34.23 ± 3.54, 32.90 ± 4.15, 32.18 ± 5.02) (p-values < 0.0001). The accuracy, sensitivity and specificity of these genes as a screening tool were: FLNA (80.8%, 88.0%, 65.8%), CLU (63.4%, 93.3%, 31.3%), CAP1 (67.2%, 83.3%, 39.1%). The tests were performed in two and three gene combinations. Results demonstrated high accuracy of 86.2%, sensitivity of 85% and specificity of 88.4% in the FLNA and CLU combination. Furthermore, after analyzed using hepatic fibrosis and non-alcoholic fatty liver as a control, the FLNA and CLU combination is shown to have accuracy of 76.9%, sensitivity of 77.6% and specificity of 75%. Also, we founded that our gene combination performs better than the current gold standard for HCC screening. We concluded that FLNA and CLU combination have high potential for being HCC novel markers. Combined with current tumor markers, further research of the gene’s expression might help identify more potential markers and improve diagnosis methods.Rathasapa PataratShoji RikuPattapon KunadirekNatthaya ChuaypenPisit TangkijvanichApiwat MutiranguraCharoenchai PuttipanyalearsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Rathasapa Patarat
Shoji Riku
Pattapon Kunadirek
Natthaya Chuaypen
Pisit Tangkijvanich
Apiwat Mutirangura
Charoenchai Puttipanyalears
The expression of FLNA and CLU in PBMCs as a novel screening marker for hepatocellular carcinoma
description Abstract Early detection improves survival and increases curative probability in hepatocellular carcinoma (HCC). Peripheral blood mononuclear cells (PBMCs) can provide an inexpensive, less-invasive and highly accurate method. The objective of this study is to find the potential marker for HCC screening, utilizing gene expression of the PBMCs. Data from the NCBI GEO database of gene expression in HCC patients and healthy donor's PBMCs was collected. As a result, GSE 49515 and GSE 58208 were found. Using both, a statistical significance test was conducted in each gene expression of each data set which resulted in 187 genes. We randomized three selected genes (FLNA, CAP1, and CLU) from the significant p-value group (p-values < 0.001). Then, a total of 76 healthy donors, 153 HCC, 20 hepatic fibrosis, 20 non-alcoholic fatty liver were collected. Quantitative RT-PCR (qRT-PCR) was performed in cDNA from all blood samples from the qRT-PCR, The Cycle threshold (Ct) value of FLNA, CLU, CAP1 of HCC group (28.47 ± 4.43, 28.01 ± 3.75, 29.64 ± 3.90) were lower than healthy group (34.23 ± 3.54, 32.90 ± 4.15, 32.18 ± 5.02) (p-values < 0.0001). The accuracy, sensitivity and specificity of these genes as a screening tool were: FLNA (80.8%, 88.0%, 65.8%), CLU (63.4%, 93.3%, 31.3%), CAP1 (67.2%, 83.3%, 39.1%). The tests were performed in two and three gene combinations. Results demonstrated high accuracy of 86.2%, sensitivity of 85% and specificity of 88.4% in the FLNA and CLU combination. Furthermore, after analyzed using hepatic fibrosis and non-alcoholic fatty liver as a control, the FLNA and CLU combination is shown to have accuracy of 76.9%, sensitivity of 77.6% and specificity of 75%. Also, we founded that our gene combination performs better than the current gold standard for HCC screening. We concluded that FLNA and CLU combination have high potential for being HCC novel markers. Combined with current tumor markers, further research of the gene’s expression might help identify more potential markers and improve diagnosis methods.
format article
author Rathasapa Patarat
Shoji Riku
Pattapon Kunadirek
Natthaya Chuaypen
Pisit Tangkijvanich
Apiwat Mutirangura
Charoenchai Puttipanyalears
author_facet Rathasapa Patarat
Shoji Riku
Pattapon Kunadirek
Natthaya Chuaypen
Pisit Tangkijvanich
Apiwat Mutirangura
Charoenchai Puttipanyalears
author_sort Rathasapa Patarat
title The expression of FLNA and CLU in PBMCs as a novel screening marker for hepatocellular carcinoma
title_short The expression of FLNA and CLU in PBMCs as a novel screening marker for hepatocellular carcinoma
title_full The expression of FLNA and CLU in PBMCs as a novel screening marker for hepatocellular carcinoma
title_fullStr The expression of FLNA and CLU in PBMCs as a novel screening marker for hepatocellular carcinoma
title_full_unstemmed The expression of FLNA and CLU in PBMCs as a novel screening marker for hepatocellular carcinoma
title_sort expression of flna and clu in pbmcs as a novel screening marker for hepatocellular carcinoma
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/9a12337f182644bfa0b70a760b398123
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