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Published in: Cancer Cell International 1/2020

01-12-2020 | Hepatocellular Carcinoma | Primary research

Random-forest algorithm based biomarkers in predicting prognosis in the patients with hepatocellular carcinoma

Authors: Lingyun Guo, Zhenjiang Wang, Yuanyuan Du, Jie Mao, Junqiang Zhang, Zeyuan Yu, Jiwu Guo, Jun Zhao, Huinian Zhou, Haitao Wang, Yanmei Gu, Yumin Li

Published in: Cancer Cell International | Issue 1/2020

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Abstract

Background

Hepatocellular carcinoma (HCC) one of the most common digestive system tumors, threatens the tens of thousands of people with high morbidity and mortality world widely. The purpose of our study was to investigate the related genes of HCC and discover their potential abilities to predict the prognosis of the patients.

Methods

We obtained RNA sequencing data of HCC from The Cancer Genome Atlas (TCGA) database and performed analysis on protein coding genes. Differentially expressed genes (DEGs) were selected. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were conducted to discover biological functions of DEGs. Protein and protein interaction (PPI) was performed to investigate hub genes. In addition, a method of supervised machine learning, recursive feature elimination (RFE) based on random forest (RF) classifier, was used to screen for significant biomarkers. And the basic experiment was conducted by lab, we constructe a clinical patients’ database, and obtained the data and results of immunohistochemistry.

Results

We identified five biomarkers with significantly high expression to predict survival risk of the HCC patients. These prognostic biomarkers included SPC25, NUF2, MCM2, BLM and AURKA. We also defined a risk score model with these biomarkers to identify the patients who is in high risk. In our single-center experiment, 95 pairs of clinical samples were used to explore the expression levels of NUF2 and BLM in HCC. Immunohistochemical staining results showed that NUF2 and BLM were significantly up-regulated in immunohistochemical staining. High expression levels of NUF2 and BLM indicated poor prognosis.

Conclusion

Our investigation provided novel prognostic biomarkers and model in HCC and aimed to improve the understanding of HCC. In the results obtained, we also conducted a part of experiments to verify the theory described earlier, The experimental results did verify our theory.
Literature
1.
go back to reference Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.
2.
go back to reference Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol. 2006;45(4):529–38.PubMedCrossRef Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol. 2006;45(4):529–38.PubMedCrossRef
3.
go back to reference Marrero JA, Kudo M, Bronowicki JP. The challenge of prognosis and staging for hepatocellular carcinoma. Oncologist. 2010;15(Suppl 4):23–33.PubMedCrossRef Marrero JA, Kudo M, Bronowicki JP. The challenge of prognosis and staging for hepatocellular carcinoma. Oncologist. 2010;15(Suppl 4):23–33.PubMedCrossRef
4.
go back to reference Fantini M, Benvenuto M, Masuelli L, Frajese GV, Tresoldi I, Modesti A, Bei R. In vitro and in vivo antitumoral effects of combinations of polyphenols, or polyphenols and anticancer drugs: perspectives on cancer treatment. Int J Mol Sci. 2015;16(5):9236–82.PubMedPubMedCentralCrossRef Fantini M, Benvenuto M, Masuelli L, Frajese GV, Tresoldi I, Modesti A, Bei R. In vitro and in vivo antitumoral effects of combinations of polyphenols, or polyphenols and anticancer drugs: perspectives on cancer treatment. Int J Mol Sci. 2015;16(5):9236–82.PubMedPubMedCentralCrossRef
5.
6.
7.
go back to reference Arwert EN, Hoste E, Watt FM. Epithelial stem cells, wound healing and cancer. Nat Rev Cancer. 2012;12(3):170–80.PubMedCrossRef Arwert EN, Hoste E, Watt FM. Epithelial stem cells, wound healing and cancer. Nat Rev Cancer. 2012;12(3):170–80.PubMedCrossRef
8.
go back to reference Astolfi A, Landuzzi L, Nicoletti G, De Giovanni C, Croci S, Palladini A, Ferrini S, Iezzi M, Musiani P, Cavallo F, et al. Gene expression analysis of immune-mediated arrest of tumorigenesis in a transgenic mouse model of HER-2/neu-positive basal-like mammary carcinoma. Am J Pathol. 2005;166(4):1205–16.PubMedPubMedCentralCrossRef Astolfi A, Landuzzi L, Nicoletti G, De Giovanni C, Croci S, Palladini A, Ferrini S, Iezzi M, Musiani P, Cavallo F, et al. Gene expression analysis of immune-mediated arrest of tumorigenesis in a transgenic mouse model of HER-2/neu-positive basal-like mammary carcinoma. Am J Pathol. 2005;166(4):1205–16.PubMedPubMedCentralCrossRef
9.
go back to reference Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer. 2003;3(6):401–10.PubMedCrossRef Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer. 2003;3(6):401–10.PubMedCrossRef
10.
go back to reference Kamb A, Gruis NA, Weaver-Feldhaus J, Liu Q, Harshman K, Tavtigian SV, Stockert E, Day RS 3rd, Johnson BE, Skolnick MH. A cell cycle regulator potentially involved in genesis of many tumor types. Science. 1994;264(5157):436–40.PubMedCrossRef Kamb A, Gruis NA, Weaver-Feldhaus J, Liu Q, Harshman K, Tavtigian SV, Stockert E, Day RS 3rd, Johnson BE, Skolnick MH. A cell cycle regulator potentially involved in genesis of many tumor types. Science. 1994;264(5157):436–40.PubMedCrossRef
12.
go back to reference Rosok O, Sioud M. Discovery of differentially expressed genes: technical considerations. Methods Mol Biol. 2007;360:115–29.PubMed Rosok O, Sioud M. Discovery of differentially expressed genes: technical considerations. Methods Mol Biol. 2007;360:115–29.PubMed
14.
go back to reference Reimers M, Carey VJ. Bioconductor: an open source framework for bioinformatics and computational biology. Methods Enzymol. 2006;411:119–34.PubMedCrossRef Reimers M, Carey VJ. Bioconductor: an open source framework for bioinformatics and computational biology. Methods Enzymol. 2006;411:119–34.PubMedCrossRef
15.
go back to reference Du J, Yuan Z, Ma Z, Song J, Xie X, Chen Y. KEGG-PATH: Kyoto encyclopedia of genes and genomes-based pathway analysis using a path analysis model. Mol BioSyst. 2014;10(9):2441–7.PubMedCrossRef Du J, Yuan Z, Ma Z, Song J, Xie X, Chen Y. KEGG-PATH: Kyoto encyclopedia of genes and genomes-based pathway analysis using a path analysis model. Mol BioSyst. 2014;10(9):2441–7.PubMedCrossRef
16.
go back to reference Gene Ontology C. The Gene Ontology (GO) project in 2006. Nucleic Acids Res. 2006;34(Database issue):D322–6.CrossRef Gene Ontology C. The Gene Ontology (GO) project in 2006. Nucleic Acids Res. 2006;34(Database issue):D322–6.CrossRef
17.
go back to reference Szklarczyk D, Morris JH, Cook H, Kuhn M, Wyder S, Simonovic M, Santos A, Doncheva NT, Roth A, Bork P, et al. The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res. 2017;45(D1):D362–8.PubMedCrossRef Szklarczyk D, Morris JH, Cook H, Kuhn M, Wyder S, Simonovic M, Santos A, Doncheva NT, Roth A, Bork P, et al. The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res. 2017;45(D1):D362–8.PubMedCrossRef
18.
go back to reference Le TT, Simmons WK, Misaki M, Bodurka J, White BC, Savitz J, McKinney BA. Differential privacy-based evaporative cooling feature selection and classification with relief-F and random forests. Bioinformatics. 2017;33(18):2906–13.PubMedPubMedCentralCrossRef Le TT, Simmons WK, Misaki M, Bodurka J, White BC, Savitz J, McKinney BA. Differential privacy-based evaporative cooling feature selection and classification with relief-F and random forests. Bioinformatics. 2017;33(18):2906–13.PubMedPubMedCentralCrossRef
19.
go back to reference Ravishankar H, Madhavan R, Mullick R, Shetty T, Marinelli L, Joel SE. Recursive feature elimination for biomarker discovery in resting-state functional connectivity. Conf Proc. 2016;2016:4071–4. Ravishankar H, Madhavan R, Mullick R, Shetty T, Marinelli L, Joel SE. Recursive feature elimination for biomarker discovery in resting-state functional connectivity. Conf Proc. 2016;2016:4071–4.
20.
go back to reference Zinkin NT, Grall F, Bhaskar K, Otu HH, Spentzos D, Kalmowitz B, Wells M, Guerrero M, Asara JM, Libermann TA, et al. Serum proteomics and biomarkers in hepatocellular carcinoma and chronic liver disease. Clin Cancer Res. 2008;14(2):470–7.PubMedCrossRef Zinkin NT, Grall F, Bhaskar K, Otu HH, Spentzos D, Kalmowitz B, Wells M, Guerrero M, Asara JM, Libermann TA, et al. Serum proteomics and biomarkers in hepatocellular carcinoma and chronic liver disease. Clin Cancer Res. 2008;14(2):470–7.PubMedCrossRef
21.
go back to reference Heo M, Maslov S, Shakhnovich E. Topology of protein interaction network shapes protein abundances and strengths of their functional and nonspecific interactions. Proc Natl Acad Sci USA. 2011;108(10):4258–63.PubMedCrossRef Heo M, Maslov S, Shakhnovich E. Topology of protein interaction network shapes protein abundances and strengths of their functional and nonspecific interactions. Proc Natl Acad Sci USA. 2011;108(10):4258–63.PubMedCrossRef
23.
go back to reference Kaneko N, Miura K, Gu Z, Karasawa H, Ohnuma S, Sasaki H, Tsukamoto N, Yokoyama S, Yamamura A, Nagase H, et al. siRNA-mediated knockdown against CDCA1 and KNTC2, both frequently overexpressed in colorectal and gastric cancers, suppresses cell proliferation and induces apoptosis. Biochem Biophys Res Commun. 2009;390(4):1235–40.PubMedCrossRef Kaneko N, Miura K, Gu Z, Karasawa H, Ohnuma S, Sasaki H, Tsukamoto N, Yokoyama S, Yamamura A, Nagase H, et al. siRNA-mediated knockdown against CDCA1 and KNTC2, both frequently overexpressed in colorectal and gastric cancers, suppresses cell proliferation and induces apoptosis. Biochem Biophys Res Commun. 2009;390(4):1235–40.PubMedCrossRef
24.
go back to reference Chen J, Rajasekaran M, Xia H, Zhang X, Kong SN, Sekar K, Seshachalam VP, Deivasigamani A, Goh BK, Ooi LL, et al. The microtubule-associated protein PRC1 promotes early recurrence of hepatocellular carcinoma in association with the Wnt/beta-catenin signalling pathway. Gut. 2016;65(9):1522–34.PubMedPubMedCentralCrossRef Chen J, Rajasekaran M, Xia H, Zhang X, Kong SN, Sekar K, Seshachalam VP, Deivasigamani A, Goh BK, Ooi LL, et al. The microtubule-associated protein PRC1 promotes early recurrence of hepatocellular carcinoma in association with the Wnt/beta-catenin signalling pathway. Gut. 2016;65(9):1522–34.PubMedPubMedCentralCrossRef
25.
go back to reference Davies RJ, Freeman A, Morris LS, Bingham S, Dilworth S, Scott I, Laskey RA, Miller R, Coleman N. Analysis of minichromosome maintenance proteins as a novel method for detection of colorectal cancer in stool. Lancet. 2002;359(9321):1917–9.PubMedCrossRef Davies RJ, Freeman A, Morris LS, Bingham S, Dilworth S, Scott I, Laskey RA, Miller R, Coleman N. Analysis of minichromosome maintenance proteins as a novel method for detection of colorectal cancer in stool. Lancet. 2002;359(9321):1917–9.PubMedCrossRef
26.
go back to reference Dudderidge TJ, Stoeber K, Loddo M, Atkinson G, Fanshawe T, Griffiths DF, Williams GH. Mcm2, Geminin, and KI67 define proliferative state and are prognostic markers in renal cell carcinoma. Clin Cancer Res. 2005;11(7):2510–7.PubMedCrossRef Dudderidge TJ, Stoeber K, Loddo M, Atkinson G, Fanshawe T, Griffiths DF, Williams GH. Mcm2, Geminin, and KI67 define proliferative state and are prognostic markers in renal cell carcinoma. Clin Cancer Res. 2005;11(7):2510–7.PubMedCrossRef
27.
go back to reference Majid S, Dar AA, Saini S, Chen Y, Shahryari V, Liu J, Zaman MS, Hirata H, Yamamura S, Ueno K, et al. Regulation of minichromosome maintenance gene family by microRNA-1296 and genistein in prostate cancer. Cancer Res. 2010;70(7):2809–18.PubMedCrossRef Majid S, Dar AA, Saini S, Chen Y, Shahryari V, Liu J, Zaman MS, Hirata H, Yamamura S, Ueno K, et al. Regulation of minichromosome maintenance gene family by microRNA-1296 and genistein in prostate cancer. Cancer Res. 2010;70(7):2809–18.PubMedCrossRef
28.
go back to reference Abe S, Kurata M, Suzuki S, Yamamoto K, Aisaki K, Kanno J, Kitagawa M. Minichromosome maintenance 2 bound with retroviral Gp70 is localized to cytoplasm and enhances DNA-damage-induced apoptosis. PLoS ONE. 2012;7(6):e40129.PubMedPubMedCentralCrossRef Abe S, Kurata M, Suzuki S, Yamamoto K, Aisaki K, Kanno J, Kitagawa M. Minichromosome maintenance 2 bound with retroviral Gp70 is localized to cytoplasm and enhances DNA-damage-induced apoptosis. PLoS ONE. 2012;7(6):e40129.PubMedPubMedCentralCrossRef
29.
go back to reference Hayama S, Daigo Y, Kato T, Ishikawa N, Yamabuki T, Miyamoto M, Ito T, Tsuchiya E, Kondo S, Nakamura Y. Activation of CDCA1-KNTC2, members of centromere protein complex, involved in pulmonary carcinogenesis. Cancer Res. 2006;66(21):10339–48.PubMedCrossRef Hayama S, Daigo Y, Kato T, Ishikawa N, Yamabuki T, Miyamoto M, Ito T, Tsuchiya E, Kondo S, Nakamura Y. Activation of CDCA1-KNTC2, members of centromere protein complex, involved in pulmonary carcinogenesis. Cancer Res. 2006;66(21):10339–48.PubMedCrossRef
30.
go back to reference Sethi G, Pathak HB, Zhang H, Zhou Y, Einarson MB, Vathipadiekal V, Gunewardena S, Birrer MJ, Godwin AK. An RNA interference lethality screen of the human druggable genome to identify molecular vulnerabilities in epithelial ovarian cancer. PLoS ONE. 2012;7(10):e47086.PubMedPubMedCentralCrossRef Sethi G, Pathak HB, Zhang H, Zhou Y, Einarson MB, Vathipadiekal V, Gunewardena S, Birrer MJ, Godwin AK. An RNA interference lethality screen of the human druggable genome to identify molecular vulnerabilities in epithelial ovarian cancer. PLoS ONE. 2012;7(10):e47086.PubMedPubMedCentralCrossRef
31.
go back to reference Huang SK, Qian JX, Yuan BQ, Lin YY, Ye ZX, Huang SS. SiRNA-mediated knockdown against NUF2 suppresses tumor growth and induces cell apoptosis in human glioma cells. Cell Mol Biol (Noisy-le-grand). 2014;60(4):30–6. Huang SK, Qian JX, Yuan BQ, Lin YY, Ye ZX, Huang SS. SiRNA-mediated knockdown against NUF2 suppresses tumor growth and induces cell apoptosis in human glioma cells. Cell Mol Biol (Noisy-le-grand). 2014;60(4):30–6.
32.
go back to reference Hu P, Shangguan J, Zhang L. Downregulation of NUF2 inhibits tumor growth and induces apoptosis by regulating lncRNA AF339813. Int J Clin Exp Pathol. 2015;8(3):2638–48.PubMedPubMedCentral Hu P, Shangguan J, Zhang L. Downregulation of NUF2 inhibits tumor growth and induces apoptosis by regulating lncRNA AF339813. Int J Clin Exp Pathol. 2015;8(3):2638–48.PubMedPubMedCentral
33.
go back to reference Karthigeyan D, Prasad SB, Shandilya J, Agrawal S, Kundu TK. Biology of Aurora A kinase: implications in cancer manifestation and therapy. Med Res Rev. 2011;31(5):757–93.PubMedCrossRef Karthigeyan D, Prasad SB, Shandilya J, Agrawal S, Kundu TK. Biology of Aurora A kinase: implications in cancer manifestation and therapy. Med Res Rev. 2011;31(5):757–93.PubMedCrossRef
34.
go back to reference Nikonova AS, Astsaturov I, Serebriiskii IG, Dunbrack RL Jr, Golemis EA. Aurora A kinase (AURKA) in normal and pathological cell division. Cell Mol Life Sci. 2013;70(4):661–87.PubMedCrossRef Nikonova AS, Astsaturov I, Serebriiskii IG, Dunbrack RL Jr, Golemis EA. Aurora A kinase (AURKA) in normal and pathological cell division. Cell Mol Life Sci. 2013;70(4):661–87.PubMedCrossRef
35.
go back to reference Blanco I, Kuchenbaecker K, Cuadras D, Wang X, Barrowdale D, de Garibay GR, Librado P, Sanchez-Gracia A, Rozas J, Bonifaci N, et al. Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers. PLoS ONE. 2015;10(4):e0120020.PubMedPubMedCentralCrossRef Blanco I, Kuchenbaecker K, Cuadras D, Wang X, Barrowdale D, de Garibay GR, Librado P, Sanchez-Gracia A, Rozas J, Bonifaci N, et al. Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers. PLoS ONE. 2015;10(4):e0120020.PubMedPubMedCentralCrossRef
36.
go back to reference Briassouli P, Chan F, Savage K, Reis-Filho JS, Linardopoulos S. Aurora-A regulation of nuclear factor-kappaB signaling by phosphorylation of IkappaBalpha. Cancer Res. 2007;67(4):1689–95.PubMedCrossRef Briassouli P, Chan F, Savage K, Reis-Filho JS, Linardopoulos S. Aurora-A regulation of nuclear factor-kappaB signaling by phosphorylation of IkappaBalpha. Cancer Res. 2007;67(4):1689–95.PubMedCrossRef
37.
go back to reference den Hollander J, Rimpi S, Doherty JR, Rudelius M, Buck A, Hoellein A, Kremer M, Graf N, Scheerer M, Hall MA, et al. Aurora kinases A and B are up-regulated by Myc and are essential for maintenance of the malignant state. Blood. 2010;116(9):1498–505.CrossRef den Hollander J, Rimpi S, Doherty JR, Rudelius M, Buck A, Hoellein A, Kremer M, Graf N, Scheerer M, Hall MA, et al. Aurora kinases A and B are up-regulated by Myc and are essential for maintenance of the malignant state. Blood. 2010;116(9):1498–505.CrossRef
38.
go back to reference Gustafson WC, Meyerowitz JG, Nekritz EA, Chen J, Benes C, Charron E, Simonds EF, Seeger R, Matthay KK, Hertz NT, et al. Drugging MYCN through an allosteric transition in Aurora kinase A. Cancer Cell. 2014;26(3):414–27.PubMedPubMedCentralCrossRef Gustafson WC, Meyerowitz JG, Nekritz EA, Chen J, Benes C, Charron E, Simonds EF, Seeger R, Matthay KK, Hertz NT, et al. Drugging MYCN through an allosteric transition in Aurora kinase A. Cancer Cell. 2014;26(3):414–27.PubMedPubMedCentralCrossRef
39.
go back to reference Lim KH, Brady DC, Kashatus DF, Ancrile BB, Der CJ, Cox AD, Counter CM. Aurora-A phosphorylates, activates, and relocalizes the small GTPase RalA. Mol Cell Biol. 2010;30(2):508–23.PubMedCrossRef Lim KH, Brady DC, Kashatus DF, Ancrile BB, Der CJ, Cox AD, Counter CM. Aurora-A phosphorylates, activates, and relocalizes the small GTPase RalA. Mol Cell Biol. 2010;30(2):508–23.PubMedCrossRef
40.
go back to reference Wang Y, Sun H, Wang Z, Liu M, Qi Z, Meng J, Sun J, Yang G. Aurora-A: a potential DNA repair modulator. Tumour Biol. 2014;35(4):2831–6.PubMedCrossRef Wang Y, Sun H, Wang Z, Liu M, Qi Z, Meng J, Sun J, Yang G. Aurora-A: a potential DNA repair modulator. Tumour Biol. 2014;35(4):2831–6.PubMedCrossRef
41.
go back to reference Mahankali M, Henkels KM, Speranza F, Gomez-Cambronero J. A non-mitotic role for Aurora kinase A as a direct activator of cell migration upon interaction with PLD, FAK and Src. J Cell Sci. 2015;128(3):516–26.PubMedPubMedCentralCrossRef Mahankali M, Henkels KM, Speranza F, Gomez-Cambronero J. A non-mitotic role for Aurora kinase A as a direct activator of cell migration upon interaction with PLD, FAK and Src. J Cell Sci. 2015;128(3):516–26.PubMedPubMedCentralCrossRef
42.
go back to reference Davari P, Hebert JL, Albertson DG, Huey B, Roy R, Mancianti ML, Horvai AE, McDaniel LD, Schultz RA, Epstein EH Jr. Loss of Blm enhances basal cell carcinoma and rhabdomyosarcoma tumorigenesis in Ptch1 ± mice. Carcinogenesis. 2010;31(6):968–73.PubMedCrossRef Davari P, Hebert JL, Albertson DG, Huey B, Roy R, Mancianti ML, Horvai AE, McDaniel LD, Schultz RA, Epstein EH Jr. Loss of Blm enhances basal cell carcinoma and rhabdomyosarcoma tumorigenesis in Ptch1 ± mice. Carcinogenesis. 2010;31(6):968–73.PubMedCrossRef
43.
go back to reference de Voer RM, Hahn MM, Mensenkamp AR, Hoischen A, Gilissen C, Henkes A, Spruijt L, van Zelst-Stams WA, Kets CM, Verwiel ET, et al. Deleterious germline blm mutations and the risk for early-onset colorectal cancer. Sci Rep. 2015;5:14060.PubMedPubMedCentralCrossRef de Voer RM, Hahn MM, Mensenkamp AR, Hoischen A, Gilissen C, Henkes A, Spruijt L, van Zelst-Stams WA, Kets CM, Verwiel ET, et al. Deleterious germline blm mutations and the risk for early-onset colorectal cancer. Sci Rep. 2015;5:14060.PubMedPubMedCentralCrossRef
44.
go back to reference Thompson ER, Doyle MA, Ryland GL, Rowley SM, Choong DY, Tothill RW, Thorne H, Barnes DR, Li J, kConFab, et al. Exome sequencing identifies rare deleterious mutations in DNA repair genes FANCC and BLM as potential breast cancer susceptibility alleles. PLoS Genet. 2012;8(9):e1002894.PubMedPubMedCentralCrossRef Thompson ER, Doyle MA, Ryland GL, Rowley SM, Choong DY, Tothill RW, Thorne H, Barnes DR, Li J, kConFab, et al. Exome sequencing identifies rare deleterious mutations in DNA repair genes FANCC and BLM as potential breast cancer susceptibility alleles. PLoS Genet. 2012;8(9):e1002894.PubMedPubMedCentralCrossRef
45.
go back to reference Sengupta S, Robles AI, Linke SP, Sinogeeva NI, Zhang R, Pedeux R, Ward IM, Celeste A, Nussenzweig A, Chen J, et al. Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest. J Cell Biol. 2004;166(6):801–13.PubMedPubMedCentralCrossRef Sengupta S, Robles AI, Linke SP, Sinogeeva NI, Zhang R, Pedeux R, Ward IM, Celeste A, Nussenzweig A, Chen J, et al. Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest. J Cell Biol. 2004;166(6):801–13.PubMedPubMedCentralCrossRef
Metadata
Title
Random-forest algorithm based biomarkers in predicting prognosis in the patients with hepatocellular carcinoma
Authors
Lingyun Guo
Zhenjiang Wang
Yuanyuan Du
Jie Mao
Junqiang Zhang
Zeyuan Yu
Jiwu Guo
Jun Zhao
Huinian Zhou
Haitao Wang
Yanmei Gu
Yumin Li
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01274-z

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