Journal of Shandong University (Health Sciences) ›› 2022, Vol. 60 ›› Issue (5): 50-58.doi: 10.6040/j.issn.1671-7554.0.2022.0128

Previous Articles     Next Articles

Prediction of hepatocellular carcinoma prognostic genes based on bioinformatics

LI Linlin, WANG Kai   

  1. Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
  • Published:2022-06-01

Abstract: Objective To screen hepatocellular carcinoma(HCC)prognostic genes based on bioinformatics methods and explore the action mechanism of related genes. Methods The expression of NUF2 in liver cancer tissues and normal liver tissues was studied based on the TCGA-LIHC dataset, the Gene Expression Omnibus(GEO)database, and the Ualcan database. The relationship of NUF2 expression and clinicopathological features of HCC was analyzed using the Wilcoxon rank-sum test. Survival analysis, univariate analysis of prognosis, and multivariate analysis were carried out using Kaplan-Meier method and Cox proportional risk regression model, respectively. The functional mechanisms was explored based on the GO and KEGG pathway enrichment analysis. NUF2 protein interaction network was constructed using the STRING database. The NUF2 interaction genes were analyzed using the LinkedOmics database to explore the regulatory mechanism of NUF2 in hepatocarcinogenesis. In addition, the relationship between NUF2 expression and tumor-infiltrating immune cell status was investigated using the TIMER database and CIBERSORT. Results Compared to normal liver tissues, NUF2 was significantly highly expressed in HCC tissues. Multivariable Cox regression analysis identified NUF2 as an independent risk factor in HCC, and patients with high NUF2 expression had significantly shorter overall survival than those with low NUF2 expression. In addition, the NUF2 protein interaction network was constructed by the STRING database and LinkedOmics database, and the functional analysis showed that NUF2 and its associated genes were mainly involved in nuclear division, chromosome segregation, mitosis, chemical-induced carcinogenesis, cell cycle and other processes. Finally, a high proportion of resting memory CD4T cells, activated memory CD4T cells, follicular helper T cells, regulatory T cells(Treg)and M0 macrophages was observed in patients with high NUF2 expression. Conclusion Upregulation of NUF2 in HCC tissues plays a key role in HCC development. High expression of NUF2 can serve as a potential diagnostic and prognostic marker to identify early and late HCC, improve timeliness and diagnostic and prognostic accuracy. NUF2 plays a key role in the immune mechanism during HCC tumorigenesis.

Key words: NUF2, Hepatocellular carcinoma, Prognosis, Biomarkers, Tumor immunity

CLC Number: 

  • R735.7
[1] Puccini A, Battaglin F, Iaia ML, et al. Overcoming resistance to anti-PD1 and anti-PD-L1 treatment in gastrointestinal malignancies [J]. J Immunother Cancer, 2020, 8(1): e000404.
[2] Aizarani N, Saviano A, Sagar, et al. A human liver cell atlas reveals heterogeneity and epithelial progenitors [J]. Nature, 2019, 572(7768): 199-204.
[3] Selcuk H. Prognostic factors and staging systems in hepatocellular carcinoma [J]. Exp Clin Transplant, 2017, 15(Suppl 2): 45-49.
[4] Grohmann M, Wiede F, Dodd GT. Obesity drives STAT-1-dependent NASH and STAT-3-dependent HCC [J]. Cell, 2018, 175(5): 1289-1306 e20.
[5] Petrick JL, Kelly SP, Altekruse SF, et al. Future of hepatocellular carcinoma incidence in the United States forecast through 2030 [J]. J Clin Oncol, 2016, 34(15): 1787-1794.
[6] Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data [J]. Bioinformatics, 2010, 26(1): 139-140.
[7] Gene Ontology Consortium. The Gene Ontology(GO)project in 2006 [J]. Nucleic Acids Res, 2006, 34(Database issue): D322-D326.
[8] Du J, Yuan Z, Ma Z, et al. KEGG-PATH: Kyoto encyclopedia of genes and genomes-based pathway analysis using a path analysis model [J]. Mol Biosyst, 2014, 10(9): 2441-2447.
[9] Newman AM, Liu CL, Green MR, et al. Robust enumeration of cell subsets from tissue expression profiles [J]. Nat Methods, 2015, 12(5): 453-457.
[10] Shah P, Wolf K, Lammerding J. Bursting the bubble-nuclear envelope rupture as a path to genomic instability? [J]. Trends Cell Biol, 2017, 27(8): 546-555.
[11] Ohnuma S, Miura K, Horii A, et al. Cancer-associated splicing variants of the CDCA1 and MSMB genes expressed in cancer cell lines and surgically resected gastric cancer tissues [J]. Surgery, 2009, 145(1): 57-68.
[12] Kaneko N, Miura K, Gu Z, et al. siRNA-mediated knockdown against CDCA1 and KNTC2, both frequently overexpressed in colorectal and gastric cancers, suppresses cell proliferation and induces apoptosis [J]. Biochem Biophys Res Commun, 2009, 390(4): 1235-1240.
[13] Hayama S, Daigo Y, Kato T, et al. Activation of CDCA1-KNTC2, members of centromere protein complex, involved in pulmonary carcinogenesis [J]. Cancer Res, 2006, 66(21): 10339-10348.
[14] Kobayashi Y, Takano A, Miyagi Y, et al. Cell division cycle-associated protein 1 overexpression is essential for the malignant potential of colorectal cancers [J]. Int J Oncol, 2014, 44(1): 69-77.
[15] Bajar BT, Lam AJ, Badiee RK, et al. Fluorescent indicators for simultaneous reporting of all four cell cycle phases [J]. Nat Methods, 2016, 13(12): 993-996.
[16] Wang Y, Tan PY, Handoko YA, et al. NUF2 is a valuable prognostic biomarker to predict early recurrence of hepatocellular carcinoma after surgical resection [J]. Int J Cancer, 2019, 145(3): 662-670.
[17] Coppell JA, Richardson PG, Soiffer R, et al. Hepatic veno-occlusive disease following stem cell transplantation: incidence, clinical course, and outcome [J]. Biol Blood Marrow Transplant, 2010, 16(2): 157-168.
[18] Yang WX, Pan YY, You CG. CDK1, CCNB1, CDC20, BUB1, MAD2L1, MCM3, BUB1B, MCM2, and RFC4 may be potential therapeutic targets for hepatocellular carcinoma using integrated bioinformatic analysis [J]. Biomed Res Int, 2019, 2019: 1245072.
[19] Liu X, He Y, Li F, et al. Caspase-3 promotes genetic instability and carcinogenesis [J]. Mol Cell, 2015, 58(2): 284-296.
[20] Hamalisto S, Stahl JL, Favaro E, et al. Spatially and temporally defined lysosomal leakage facilitates mitotic chromosome segregation [J]. Nat Commun, 2020, 11(1): 229.
[21] Zhang T, Zhou Y, Qi ST, et al. Nuf2 is required for chromosome segregation during mouse oocyte meiotic maturation [J]. Cell Cycle, 2015, 14(16): 2701-2710.
[22] Mao Y. FORMIN a link between kinetochores and microtubule ends [J]. Trends Cell Biol, 2011, 21(11): 625-629.
[23] Xie X, Jiang S, Li X. Nuf2 is a prognostic-related biomarker and correlated with immune infiltrates in hepatocellular carcinoma [J]. Front Oncol, 2021, 11: 621373. doi: 10.3389/fonc.2021.621373.
[24] Lampel J, Shapira Z. Judgmental errors,interactive norms, and the difficulty of detecting strategic surprises [J]. Organ Sci, 2001, 12(5): 599-611.
[25] Numnum TM, Makhija S, Lu B, et al. Improved anti-tumor therapy based upon infectivity-enhanced adenoviral delivery of RNA interference in ovarian carcinoma cell lines [J]. Gynecol Oncol, 2008, 108(1): 34-41.
[26] Harao M, Hirata S, Irie A, et al. HLA-A2-restricted CTL epitopes of a novel lung cancer-associated cancer testis antigen, cell division cycle associated 1, can induce tumor-reactive CTL [J]. Int J Cancer, 2008, 123(11): 2616-2625.
[27] Duffy AG, Makarova-Rusher OV, Greten TF. The case for immune-based approaches in biliary tract carcinoma [J]. Hepatology, 2016, 64(5): 1785-1791.
[28] Obara W, Sato F, Takeda K, et al. Phase I clinical trial of cell division associated 1(CDCA1)peptide vaccination for castration resistant prostate cancer [J]. Cancer Sci, 2017, 108(7): 1452-1457.
[29] Galon J, Costes A, Sanchez-Cabo F, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome [J]. Science, 2006, 313(5795): 1960-1964.
[1] YU De-Xin, CAEI Ti-Gong, MA Xiang-Xing, ZHANG Xiao-Ming, LI Chuan-Fu. Angiogenesis and maturation of hepatocellular carcinoma [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2209, 47(6): 51-54.
[2] ZHENG Su, CHEN Shuhua, LI Hua, DENG Jie, CHEN Chunhong, WANG Xiaohui, FENG Weixing, HAN Xiaodi, ZHANG Yujia, LI Na, LI Mo, FANG Fang. Correlation between EEG variations and BASED evaluation of the efficacy of ACTH treatment in 54 cases of infantile spasms [J]. Journal of Shandong University (Health Sciences), 2022, 60(9): 91-96.
[3] WANG Lihui, GAO Min, KONG Beihua. Angiosarcoma of the uterus: a report of 2 cases and literature review [J]. Journal of Shandong University (Health Sciences), 2022, 60(9): 108-112.
[4] HE Shiqing, LI Wanwan, DONG Shuqing, MOU Jingyi, LIU Yuying, WEI Siyu, LIU Zhao, ZHANG Jiaxin. Construction of a prognostic risk model of pyroptosis-related genes in breast cancer based on database [J]. Journal of Shandong University (Health Sciences), 2022, 60(8): 34-43.
[5] ZHANG Yufeng, XU Min, XING Xiuli, PANG Shuguang, HU Keqing. Epidemiological characteristics of 689 patients with non-ST-segment elevation myocardial infarction [J]. Journal of Shandong University (Health Sciences), 2022, 60(7): 118-122.
[6] ZUO Liping, JIANG Fengyang, ZHOU Binbin, FAN Jinlei, LIANG Yongfeng, DENG Zhanhao, YU Dexin. Value of preoperative multiphase MRI for predicting microvascular invasion and early recurrence of 169 hepatocellular carcinoma [J]. Journal of Shandong University (Health Sciences), 2022, 60(3): 89-95.
[7] SUN Zhenguo, TIAN Hui. Optimization of the procedures in minimally invasive esophagectomy: the Qilu practices [J]. Journal of Shandong University (Health Sciences), 2022, 60(11): 33-37.
[8] ZHU Yongcun, ZHAO Xiushi, SUN Nannan, YAO Zhigang, ZHOU Xingchen, MU Kun. Prostate clear cell adenocarcinomas: a report of 3 cases and literature review [J]. Journal of Shandong University (Health Sciences), 2022, 60(11): 102-107.
[9] SHI Xiaohan, LI Huayu, LI Feng. Prognostic factors of elderly patients with glioblastoma treated with Stupp treatment [J]. Journal of Shandong University (Health Sciences), 2022, 60(10): 42-48.
[10] XIU Dejian, GAO Zhengwen, SONG Tingting, CUI Nan, CUI Jing, SUN Jianping. Genes associated with cervical cancer by integrated bioinformatics analysis [J]. Journal of Shandong University (Health Sciences), 2022, 60(10): 99-109.
[11] CHEN Liyu, XIAO Juan, LYU Xianzhong, DUAN Baomin, HONG Fanzhen. Risk factors influencing prognosis of lower extremity deep vein thrombosis in pregnant and parturient women [J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 38-42.
[12] TIAN Yaotian, WANG Bao, LI Yeqin, WANG Teng, TIAN Liwen, HAN Bo, WANG Cuiyan. Machine learning models based on interpretive CMR parameters can predict the prognosis of pediatric myocarditis [J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 43-49.
[13] LI Wanwan, ZHOU Wenkai, DONG Shuqing, HE Shiqing, LIU Zhao, ZHANG Jiaxin, LIU Bin. Construct of a risk assessment model of breast cancer immune-related lncRNAs based on the database information [J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 74-84.
[14] CHU Yan, LIU Duanrui, ZHU Wenshuai, FAN Rong, MA Xiaoli, WANG Yunshan, JIA Yanfei. Expressions of DNA methyltransferases in gastric cancer and their clinical significance [J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 1-9.
[15] MI Qi, SHI Shuang, LI Juan, LI Peilong, DU Lutao, WANG Chuanxin. Construction of circRNA-mediated ceRNA network and prognostic assessment model for bladder cancer [J]. Journal of Shandong University (Health Sciences), 2021, 59(6): 94-102.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] SHI Shuang, LI Juan, MI Qi, WANG Yunshan, DU Lutao, WANG Chuanxin. Construction and application of a miRNAs prognostic risk assessment model of gastric cancer[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 47 -52 .
[2] HUANG Fei,WANG Huaijing,XING Yi,GAO Wei,LI Yonggang,XING Ziying,LI Zhenzhong. Protective effects of NGF and GM1 on primary sensory neurons in SD rat with sciatic nerve injury[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2006, 44(4): 332 -335 .
[3] LYU Longfei, LI Lin, LI Shuhai, QI Lei, LU Ming, CHENG Chuanle, TIAN Hui. Application of laparoscopic fine needle catheter jejunostomy in minimally invasive McKeown resection of esophageal cancer[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 77 -81 .
[4] SHAO Haigang, WANG Xuan, WANG Qing. Anatomy of the root canal system of mandibular first premolar in population of Shandong Province[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(9): 85 -89 .
[5] LI Wei,LI Dao-wei,YE Qian,GAO Shun-cui,JIANG Shu-juan.

Diagnostic value of transbronchial needle aspiration in paratracheal mediastinal lesions

[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(11): 1063 -1065 .
[6] WANG Xu-ping,ZHAO Ling,FENG Yu-xin,SHANG Lin-shan,LIU Jin-cheng,. [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2006, 44(6): 564 -567 .
[7] WANG Xue-ping,YANG Hong-ling. [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, (2): 213 .
[8] TANG Fang1,2, ZHANG Yingqian3, WANG Zhiqiang4, KANG Dianmin4,
WANG Jiezhen1, XUE Fuzhong1
. A 2D minimal spanning tree model of the spatial structures of natural focal disease[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2009, 47(01): 106 -110 .
[9] HUANG Sheng-yun,ZHANG Dong-sheng,ZHANG Shi-zhou,LIU Gui-jun,ZHAO Yue-ran,WANG Lai-cheng,LIU Yi-qing. Construction of recombination expression vector pIRES-CD and pIRES-TK and their expression in ACC-2 cells[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(2): 117 -123 .
[10] LI Yu-liang,WANG Yong-zheng,WANG Xiao-hua,ZHANG Fu-jun,ZHU Li-dong,ZHANG Wang-ming,LI Zheng,LI Zhen-jia,ZHANG Kai-xian. I implantation combined with Gemcitabine in the treatment of advanced pancreatic cancer[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(4): 393 -396 .