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Erschienen in: Tumor Biology 1/2016

20.08.2015 | Original Article

Pseudogene integrator complex subunit 6 pseudogene 1 (INTS6P1) as a novel plasma-based biomarker for hepatocellular carcinoma screening

verfasst von: Ka Yin Lui, Hao-ran Peng, Jin-rong Lin, Chun-hui Qiu, Hu-an Chen, Rong-dang Fu, Chang-jie Cai, Min-qiang Lu

Erschienen in: Tumor Biology | Ausgabe 1/2016

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Abstract

In this study, we aimed to determine whether the pseudogene integrator complex subunit 6 pseudogene 1 (INTS6P1) in plasma could be used as a novel approach to screen for and detect hepatocellular carcinoma (HCC). We explored the clinical role of INTS6P1: First, the expression level of INTS6P1 was measured in a cohort of 33 HCC tissue samples and adjacent normal liver tissue, next, the INTS6P1 expression was detected in the culture medium and tumor cells in a cellular experiment, and last, the diagnostic performance of INTS6P1 was examined in an independent cohort of 100 people. The expression level of INTS6P1 was remarkably downregulated in the HCC tissues compared with that in the normal liver tissues (p = 0.0066). In plasma, the INTS6P1 levels were significantly decreased in HCC patients compared with non-HCC patients (p < 0.01). Additionally, we inferred that INTS6P1 might be a prospective biomarker for screening HCC patients in which the serum-AFP levels were lower than 20 ng/ml by the area under the curve-receiver operating characteristic (AUC-ROC) analysis (p < 0.05). Pseudogene INTS6P1 could be used as a novel HCC plasma-based biomarker and might improve the accuracy of HCC screening.
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Literatur
1.
Zurück zum Zitat EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012; 56(4):908–943. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012; 56(4):908–943.
3.
Zurück zum Zitat Ercolani G, Grazi GL, Ravaioli M, Del Gaudio M, Gardini A, Cescon M, et al. Liver resection for hepatocellular carcinoma on cirrhosis: univariate and multivariate analysis of risk factors for intrahepatic recurrence. Ann Surg. 2003;237(4):536–43.PubMedPubMedCentral Ercolani G, Grazi GL, Ravaioli M, Del Gaudio M, Gardini A, Cescon M, et al. Liver resection for hepatocellular carcinoma on cirrhosis: univariate and multivariate analysis of risk factors for intrahepatic recurrence. Ann Surg. 2003;237(4):536–43.PubMedPubMedCentral
4.
Zurück zum Zitat Schwartz M, Roayaie S, Konstadoulakis M. Strategies for the management of hepatocellular carcinoma. Nat Clin Pract Oncol. 2007;4(7):424–32.CrossRefPubMed Schwartz M, Roayaie S, Konstadoulakis M. Strategies for the management of hepatocellular carcinoma. Nat Clin Pract Oncol. 2007;4(7):424–32.CrossRefPubMed
5.
Zurück zum Zitat Turati F, Edefonti V, Talamini R, Ferraroni M, Malvezzi M, Bravi F, et al. Family history of liver cancer and hepatocellular carcinoma. Hepatology. 2012;55:1416–25.CrossRefPubMed Turati F, Edefonti V, Talamini R, Ferraroni M, Malvezzi M, Bravi F, et al. Family history of liver cancer and hepatocellular carcinoma. Hepatology. 2012;55:1416–25.CrossRefPubMed
6.
Zurück zum Zitat El-Aneed A, Banoub J. Proteomics in the diagnosis of hepatocellular carcinoma: focus on high risk hepatitis B and C patients. Anticancer Res. 2006;26(5A):3293–300.PubMed El-Aneed A, Banoub J. Proteomics in the diagnosis of hepatocellular carcinoma: focus on high risk hepatitis B and C patients. Anticancer Res. 2006;26(5A):3293–300.PubMed
8.
Zurück zum Zitat Marrero JA, Su GL, Wei W, Emick D, Conjeevaram HS, Fontana RJ, et al. Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in american patients. Hepatology. 2003;37(5):1114–21.CrossRefPubMed Marrero JA, Su GL, Wei W, Emick D, Conjeevaram HS, Fontana RJ, et al. Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in american patients. Hepatology. 2003;37(5):1114–21.CrossRefPubMed
9.
Zurück zum Zitat Lok AS, Seeff LB, Morgan TR, di Bisceglie AM, Sterling RK, Curto TM, et al. Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease. Gastroenterology. 2009;136(1):138–48.CrossRefPubMed Lok AS, Seeff LB, Morgan TR, di Bisceglie AM, Sterling RK, Curto TM, et al. Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease. Gastroenterology. 2009;136(1):138–48.CrossRefPubMed
11.
Zurück zum Zitat Di Bisceglie AM, Hoofnagle JH. Elevations in serum alpha-fetoprotein levels in patients with chronic hepatitis B. Cancer. 1989;64(10):2117–20.CrossRefPubMed Di Bisceglie AM, Hoofnagle JH. Elevations in serum alpha-fetoprotein levels in patients with chronic hepatitis B. Cancer. 1989;64(10):2117–20.CrossRefPubMed
12.
Zurück zum Zitat Sheu JC, Sung JL, Chen DS, Lai MY, Wang TH, Yu JY, et al. Early detection of hepatocellular carcinoma by real-time ultrasonography. A prospective study. Cancer. 1985;56(3):660–6.CrossRefPubMed Sheu JC, Sung JL, Chen DS, Lai MY, Wang TH, Yu JY, et al. Early detection of hepatocellular carcinoma by real-time ultrasonography. A prospective study. Cancer. 1985;56(3):660–6.CrossRefPubMed
13.
Zurück zum Zitat Song ZZ. Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma. Hepatology. 2008;47(6):2145–56.CrossRefPubMed Song ZZ. Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma. Hepatology. 2008;47(6):2145–56.CrossRefPubMed
14.
Zurück zum Zitat Schwarzenbach H, Hoon DS, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer. 2011;11(6):426–37.CrossRefPubMed Schwarzenbach H, Hoon DS, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer. 2011;11(6):426–37.CrossRefPubMed
15.
Zurück zum Zitat Wang KC, Yang YW, Liu B, Sanyal A, Corces-Zimmerman R, Chen Y, et al. A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature. 2011;472:120–4.CrossRefPubMedPubMedCentral Wang KC, Yang YW, Liu B, Sanyal A, Corces-Zimmerman R, Chen Y, et al. A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature. 2011;472:120–4.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10(3):155–9.CrossRefPubMed Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10(3):155–9.CrossRefPubMed
17.
Zurück zum Zitat Ma L, Bajic VB, Zhang Z. On the classification of long non-coding RNAs. RNA Biol. 2013; 10. Ma L, Bajic VB, Zhang Z. On the classification of long non-coding RNAs. RNA Biol. 2013; 10.
18.
Zurück zum Zitat Wang J, Liu X, Wu H, Ni P, Gu Z, Qiao Y, et al. CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer. Nucleic Acids Res. 2010;38:5366–83.CrossRefPubMedPubMedCentral Wang J, Liu X, Wu H, Ni P, Gu Z, Qiao Y, et al. CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer. Nucleic Acids Res. 2010;38:5366–83.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Tian Y, Yang W, Song J, Wu Y, Ni B. Hepatitis B virus x protein-induced aberrant epigenetic modifications contributing to human hepatocellular carcinoma pathogenesis. Mol Cell Biol. 2013;33:2810–6.CrossRefPubMedPubMedCentral Tian Y, Yang W, Song J, Wu Y, Ni B. Hepatitis B virus x protein-induced aberrant epigenetic modifications contributing to human hepatocellular carcinoma pathogenesis. Mol Cell Biol. 2013;33:2810–6.CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Wapinski O, Chang HY. Long noncoding RNAs and human disease. Trends Cell Biol. 2011;21:354–61.CrossRefPubMed Wapinski O, Chang HY. Long noncoding RNAs and human disease. Trends Cell Biol. 2011;21:354–61.CrossRefPubMed
21.
Zurück zum Zitat He Y, Meng X-M, Huang C, Wu B-M, Zhang L, Lv X-W, et al. Long noncoding RNAs: novel insights into hepatocelluar carcinoma. Cancer Lett. 2014;344:20–7.CrossRefPubMed He Y, Meng X-M, Huang C, Wu B-M, Zhang L, Lv X-W, et al. Long noncoding RNAs: novel insights into hepatocelluar carcinoma. Cancer Lett. 2014;344:20–7.CrossRefPubMed
22.
Zurück zum Zitat Peng H, Ishida M, Li L, Saito A, et al. Pseudogene INTS6P1 regulates its cognate gene INTS6 through competitive binding of miR-17-5p in hepatocellular carcinoma. Oncotarget. 2015;6(8):5666–77.CrossRefPubMedPubMedCentral Peng H, Ishida M, Li L, Saito A, et al. Pseudogene INTS6P1 regulates its cognate gene INTS6 through competitive binding of miR-17-5p in hepatocellular carcinoma. Oncotarget. 2015;6(8):5666–77.CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Liu R, Chen X, Du Y, et al. SerummicroRNA expression profile as a biomarker in the diagnosis and prognosis of pancreatic cancer. Clin Chem. 2012;58:610–8.CrossRefPubMed Liu R, Chen X, Du Y, et al. SerummicroRNA expression profile as a biomarker in the diagnosis and prognosis of pancreatic cancer. Clin Chem. 2012;58:610–8.CrossRefPubMed
24.
Zurück zum Zitat Ren S, Wang F, Shen J, et al. Long non-coding RNA metastasis associated in lung adenocarcinoma transcript 1 derived miniRNA as a novel plasma-based biomarker for diagnosing prostate cancer. Eur J Cancer. 2013;49:2949–59.CrossRefPubMed Ren S, Wang F, Shen J, et al. Long non-coding RNA metastasis associated in lung adenocarcinoma transcript 1 derived miniRNA as a novel plasma-based biomarker for diagnosing prostate cancer. Eur J Cancer. 2013;49:2949–59.CrossRefPubMed
Metadaten
Titel
Pseudogene integrator complex subunit 6 pseudogene 1 (INTS6P1) as a novel plasma-based biomarker for hepatocellular carcinoma screening
verfasst von
Ka Yin Lui
Hao-ran Peng
Jin-rong Lin
Chun-hui Qiu
Hu-an Chen
Rong-dang Fu
Chang-jie Cai
Min-qiang Lu
Publikationsdatum
20.08.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 1/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3899-8

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