Analysis of survival prediction value of MCM gene family in hepatocellular carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

JIA Yu , CHEN Yan ,  LIU Jiansheng

Department of General Surgery, The First Hospital of Shanxi Medical University, Taiyuan 030001, P. R. China;

Corresponding author：

LIU Jiansheng, Email: 147542533@qq.com

Keywords：

hepatocellular carcinoma; microchromosome maintenance protein; prognostic model; nomogram

DOI：

10.7507/1007-9424.202010026

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To study the differential expression of minichromosome maintenance protein (MCM) gene family in hepatocellular carcinoma (HCC) and to explore its survival predictive value.Methods Transcriptome data, clinical data, and survival information of patients with HCC were extracted from The Cancer Genome Atlas (TCGA), and the differential expression of MCM gene was analyzed. The prognostic value of differentially expressed of MCM gene was studied by Cox proportional hazards regression model, the prognostic model and risk score system were constructed. On the basis of risk score, a number of indicators were included to construct a nomogram to predict the3- and 5-year survival probability of HCC patients, and to verify and evaluate their predictive ability and accuracy.Results The expressions of MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, MCM8, and MCM10 in HCC tissues were higher than those of normal liver tissues (P<0.05), and univariate analysis showed that they were all related to prognosis (P<0.05). Multivariate analysis showed that MCM6 and MCM10 were independent factors affecting survival of HCC patients (P<0.05). Through multivariate analysis, a prognostic model consisting of MCM6, MCM8, and MCM10 was constructed, and a risk scoring system was established. It had been verified that this risk score was an independent risk factor affecting the prognosis of patients with HCC, and the prognosis of patients with high scores were worse than those of patients with low scores (P<0.001). We used TNM stage, T stage, and risk score to construct a nomogram with a consistency index (C index) of 0.723 and draw a time-dependent receiver operating characteristic curve, the results showed that area under the curve of 3- and 5-year were 0.731 and 0.704, respectively.Conclusions MCM6,MCM8, and MCM10 in the MCM gene family have important prognostic value in HCC. The nomogram constructed in this study can better predict the survival probability of HCC patients.

Citation： JIA Yu, CHEN Yan, LIU Jiansheng. Analysis of survival prediction value of MCM gene family in hepatocellular carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(7): 898-903. doi: 10.7507/1007-9424.202010026 Copy

1.	Bray F, Ferlay J, Soerjomataram I, et al. 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.	Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
3.	文天夫. 转化切除是提高肝细胞癌切除率的重要途径. 中国普外基础与临床杂志, 2020, 27(2): 133-136.
4.	Brewster AS, Chen XS. Insights into the MCM functional mechanism: lessons learned from the archaeal MCM complex. Crit Rev Biochem Mol Biol, 2010, 45(3): 243-256.
5.	Kearsey SE, Labib K. MCM proteins: evolution, properties, and role in DNA replication. Biochim Biophys Acta, 1998, 1398(2): 113-136.
6.	Kwok HF, Zhang SD, McCrudden CM, et al. Prognostic significance of minichromosome maintenance proteins in breast cancer. Am J Cancer Res, 2014, 5(1): 52-71.
7.	Liu K, Kang M, Liao X, et al. Genome-wide investigation of the clinical significance and prospective molecular mechanism of minichromosome maintenance protein family genes in patients with lung adenocarcinoma. PLoS One, 2019, 14(7): e0219467.
8.	Saydam O, Senol O, Schaaij-Visser TB, et al. Comparative protein profiling reveals minichromosome maintenance (MCM) proteins as novel potential tumor markers for meningiomas. J Proteome Res, 2010, 9(1): 485-494.
9.	Yang JY, Li D, Zhang Y, et al. The expression of MCM7 is a useful biomarker in the early diagnostic of gastric cancer. Pathol Oncol Res, 2018, 24(2): 367-372.
10.	詹启敏, 陈杰. 细胞周期与肿瘤转化医学. 中国肿瘤临床, 2014, 41(1): 1-7.
11.	Wang Y, Chen H, Zhang J, et al. MCM family in gastrointestinal cancer and other malignancies: From functional characterization to clinical implication. Biochim Biophys Acta Rev Cancer, 2020, 1874(2): 188415.
12.	Riera A, Barbon M, Noguchi Y, et al. From structure to mechanism-understanding initiation of DNA replication. Genes Dev, 2017, 31(11): 1073-1088.
13.	Powell SK, MacAlpine HK, Prinz JA, et al. Dynamic loading and redistribution of the Mcm2-7 helicase complex through the cell cycle. EMBO J, 2015, 34(4): 531-543.
14.	Baltin J, Leist S, Odronitz F, et al. DNA replication in protein extracts from human cells requires ORC and Mcm proteins. J Biol Chem, 2006, 281(18): 12428-12435.
15.	Natsume T, Nishimura K, Minocherhomji S, et al. Acute inactivation of the replicative helicase in human cells triggers MCM8-9-dependent DNA synthesis. Genes Dev, 2017, 31(8): 816-829.
16.	Maiorano D, Lutzmann M, Méchali M. MCM proteins and DNA replication. Curr Opin Cell Biol, 2006, 18(2): 130-136.
17.	Lee C, Liachko I, Bouten R, et al. Alternative mechanisms for coordinating polymerase alpha and MCM helicase. Mol Cell Biol, 2010, 30(2): 423-435.
18.	Douglas ME, Diffley JF. Recruitment of MCM10 to sites of replication initiation requires direct binding to the minichromosome maintenance (MCM) complex. J Biol Chem, 2016, 291(11): 5879-5888.
19.	Liu Z, Li J, Chen J, et al. MCM family in HCC: MCM6 indicates adverse tumor features and poor outcomes and promotes S/G2 cell cycle progression. BMC Cancer, 2018, 18(1): 200.
20.	Liu M, Hu Q, Tu M, et al. MCM6 promotes metastasis of hepatocellular carcinoma via MEK/ERK pathway and serves as a novel serum biomarker for early recurrence. J Exp Clin Cancer Res, 2018, 37(1): 10.
21.	Peng YP, Zhu Y, Yin LD, et al. The expression and prognostic roles of MCMs in pancreatic cancer. PLoS One, 2016, 11(10): e0164150.
22.	Morii I, Iwabuchi Y, Mori S, et al. Inhibiting the MCM8-9 complex selectively sensitizes cancer cells to cisplatin and olaparib. Cancer Sci, 2019, 110(3): 1044-1053.
23.	Das M, Prasad SB, Yadav SS, et al. Over expression of minichromosome maintenance genes is clinically correlated to cervical carcinogenesis. PLoS One, 2013, 8(7): e69607.
24.	Cui F, Hu J, Ning S, et al. Overexpression of MCM10 promotes cell proliferation and predicts poor prognosis in prostate cancer. Prostate, 2018, 78(16): 1299-1310.

1. Bray F, Ferlay J, Soerjomataram I, et al. 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. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
3. 文天夫. 转化切除是提高肝细胞癌切除率的重要途径. 中国普外基础与临床杂志, 2020, 27(2): 133-136.
4. Brewster AS, Chen XS. Insights into the MCM functional mechanism: lessons learned from the archaeal MCM complex. Crit Rev Biochem Mol Biol, 2010, 45(3): 243-256.
5. Kearsey SE, Labib K. MCM proteins: evolution, properties, and role in DNA replication. Biochim Biophys Acta, 1998, 1398(2): 113-136.
6. Kwok HF, Zhang SD, McCrudden CM, et al. Prognostic significance of minichromosome maintenance proteins in breast cancer. Am J Cancer Res, 2014, 5(1): 52-71.
7. Liu K, Kang M, Liao X, et al. Genome-wide investigation of the clinical significance and prospective molecular mechanism of minichromosome maintenance protein family genes in patients with lung adenocarcinoma. PLoS One, 2019, 14(7): e0219467.
8. Saydam O, Senol O, Schaaij-Visser TB, et al. Comparative protein profiling reveals minichromosome maintenance (MCM) proteins as novel potential tumor markers for meningiomas. J Proteome Res, 2010, 9(1): 485-494.
9. Yang JY, Li D, Zhang Y, et al. The expression of MCM7 is a useful biomarker in the early diagnostic of gastric cancer. Pathol Oncol Res, 2018, 24(2): 367-372.
10. 詹启敏, 陈杰. 细胞周期与肿瘤转化医学. 中国肿瘤临床, 2014, 41(1): 1-7.
11. Wang Y, Chen H, Zhang J, et al. MCM family in gastrointestinal cancer and other malignancies: From functional characterization to clinical implication. Biochim Biophys Acta Rev Cancer, 2020, 1874(2): 188415.
12. Riera A, Barbon M, Noguchi Y, et al. From structure to mechanism-understanding initiation of DNA replication. Genes Dev, 2017, 31(11): 1073-1088.
13. Powell SK, MacAlpine HK, Prinz JA, et al. Dynamic loading and redistribution of the Mcm2-7 helicase complex through the cell cycle. EMBO J, 2015, 34(4): 531-543.
14. Baltin J, Leist S, Odronitz F, et al. DNA replication in protein extracts from human cells requires ORC and Mcm proteins. J Biol Chem, 2006, 281(18): 12428-12435.
15. Natsume T, Nishimura K, Minocherhomji S, et al. Acute inactivation of the replicative helicase in human cells triggers MCM8-9-dependent DNA synthesis. Genes Dev, 2017, 31(8): 816-829.
16. Maiorano D, Lutzmann M, Méchali M. MCM proteins and DNA replication. Curr Opin Cell Biol, 2006, 18(2): 130-136.
17. Lee C, Liachko I, Bouten R, et al. Alternative mechanisms for coordinating polymerase alpha and MCM helicase. Mol Cell Biol, 2010, 30(2): 423-435.
18. Douglas ME, Diffley JF. Recruitment of MCM10 to sites of replication initiation requires direct binding to the minichromosome maintenance (MCM) complex. J Biol Chem, 2016, 291(11): 5879-5888.
19. Liu Z, Li J, Chen J, et al. MCM family in HCC: MCM6 indicates adverse tumor features and poor outcomes and promotes S/G2 cell cycle progression. BMC Cancer, 2018, 18(1): 200.
20. Liu M, Hu Q, Tu M, et al. MCM6 promotes metastasis of hepatocellular carcinoma via MEK/ERK pathway and serves as a novel serum biomarker for early recurrence. J Exp Clin Cancer Res, 2018, 37(1): 10.
21. Peng YP, Zhu Y, Yin LD, et al. The expression and prognostic roles of MCMs in pancreatic cancer. PLoS One, 2016, 11(10): e0164150.
22. Morii I, Iwabuchi Y, Mori S, et al. Inhibiting the MCM8-9 complex selectively sensitizes cancer cells to cisplatin and olaparib. Cancer Sci, 2019, 110(3): 1044-1053.
23. Das M, Prasad SB, Yadav SS, et al. Over expression of minichromosome maintenance genes is clinically correlated to cervical carcinogenesis. PLoS One, 2013, 8(7): e69607.
24. Cui F, Hu J, Ning S, et al. Overexpression of MCM10 promotes cell proliferation and predicts poor prognosis in prostate cancer. Prostate, 2018, 78(16): 1299-1310.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Analysis of survival prediction value of MCM gene family in hepatocellular carcinoma

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content