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中华普外科手术学杂志(电子版) ›› 2021, Vol. 15 ›› Issue (04) : 380 -383. doi: 10.3877/cma.j.issn.1674-3946.2021.04.008

论著

利用TCGA数据库分析AKR1B10在肝癌中的表达及临床意义
刘荣强1, 郑世扬2, 代天星3, 邓铭彬3, 林国桢4, 周朝荣5, 汪国营6,†()   
  1. 1. 510030　广州，广州医科大学附属第一医院肝胆外科
    2. 510145　广州，广州医科大学附属第三医院乳腺外科
    3. 510630　广州，中山大学附属第三医院肝脏外科
    4. 518055　深圳，南方科技大学附属第二医院肝胆外科
    5. 510220　广州，广州医科大学附属第二医院普外科
    6. 510030　广州，广州医科大学附属第一医院肝胆外科；510630　广州，中山大学附属第三医院肝脏外科
  • 收稿日期:2020-05-26 出版日期:2021-08-17
  • 通信作者: 汪国营

Expression and clinical significance of AKR1B10 in hepatocellular carcinoma by TCGA database analysis

Rongqiang Liu1, Shiyang Zheng2, Tianxing Dai3, Minbing Deng3, Guozhen Lin4, Chaorong Zhou5, Guoying Wang6,†()   

  1. 1. Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510030, China
    2. Department of Breast surgery, the third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510145, China
    3. Department of Hepatobiliary Surgery, Liver Transplantion Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
    4. Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen 518055, China
    5. Department of Gastrointestinal Surgery, the second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510220, China
    6. Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510030, China; Department of Hepatobiliary Surgery, Liver Transplantion Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
  • Received:2020-05-26 Published:2021-08-17
  • Corresponding author: Guoying Wang
  • Supported by:
    National Natural Science Foundation of China(81470870, 81670601, 81770648); Natural Science Foundation of Guangdong Province(2016A030313278, 2015A030313038 and 2015A030312013); Science and Technology Plan Project of Guangdong Province(2014A020211015, 2017B020209004); Science and Technology Plan Project of Guangzhou(2014J4100183); Major science and technology projects for the 13th five-year plan(2017zx10203205-006-001)
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刘荣强, 郑世扬, 代天星, 邓铭彬, 林国桢, 周朝荣, 汪国营. 利用TCGA数据库分析AKR1B10在肝癌中的表达及临床意义[J/OL]. 中华普外科手术学杂志(电子版), 2021, 15(04): 380-383.

Rongqiang Liu, Shiyang Zheng, Tianxing Dai, Minbing Deng, Guozhen Lin, Chaorong Zhou, Guoying Wang. Expression and clinical significance of AKR1B10 in hepatocellular carcinoma by TCGA database analysis[J/OL]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2021, 15(04): 380-383.

目的

研究醛酮还原酶家族1成员B10 (AKR1B10)在肝癌中的表达情况及临床价值，并探讨AKR1B10参与肝癌发生、发展的机制。

方法

自2019年10月从肿瘤基因组图谱(TCGA)数据库中下载肝癌数据集，获取AKR1B10基因表达谱及临床信息。分析424例样本中AKR1B10的表达与肝癌预后及临床病理特征之间的相关性。采用基因富集化分析(GSEA)方法预测AKR1B10在肝癌中的调控通路。使用SPSS22.0进行统计分析。肝癌组织与癌旁组织表达差异采用t检验。临床病理参数相关性分析，组间比较采用χ2检验。单因素和多因素分析采用Cox回归模型。P<0.05差异有统计学意义。

结果

在TCGA数据库中，AKR1B10在肝癌组织中高表达，高表达AKR1B10患者总体生存期明显低于AKR1B10低表达患者(P＝0.006)。多因素分析进一步显示AKR1B10表达状态是影响肝癌预后的独立危险因素(P＝0.003)。AKR1B10表达富集到Toll样受体信号通路、NOD样受体信号通路、氨酰tRNA生物合成、谷胱甘肽代谢等基因集。

结论

肝癌组织AKR1B10 mRNA高表达是一种预后不良的危险因素。RT-PCR可快速检测肝癌组织中其表达情况来评估患者预后，是预测肝癌患者预后较好的新指标。

关键词: 癌, 肝细胞, 醛酮还原酶家族1成员B10, 基因表达, 肿瘤基因组图谱, 临床意义
Objective

To investigate the expression and clinical value of AKR1B10 in hepatocellular carcinoma, and to explore the role of AKR1B10 in the development of hepatocellular carcinoma.

Methods

The hepatocellular carcinoma dataset was downloaded from the Cancer Gene Map (TCGA) database to obtain the AKR1B10 gene expression profile and clinical information on October 15, 2019. Thecorrelation between the expression of AKR1B10 in 424 samples and the prognosis and clinicopathological features of hepatocellular carcinoma were analyzed. Gene-enrichment analysis (GSEA) were used to predict the regulatory pathway of AKR1B10 in hepatocellular carcinoma. Statistical analysis was performed by using SPSS22.0 software Independent t test was used to detect the difference of expression between liver cancer tissues and adjacent tissues. The correlation of clinicopathological parameters between two groups was analyzed by chi-square test. Cox regression model was used for univariate and multivariate analysis. A P value of<0.05 was considered as statistically significant difference.

Results

AKR1B10 was highly expressed in hepatocellular carcinoma, and the overall survival rate of patients with high expression of AKR1B10 was significantly lower than that of patients with low expression of AKR1B10 (P=0.006). Multivariate analysis further indicated that AKR1B10 expression was an independent risk factor affecting the prognosis of HCC (P=0.003). AKR1B10 expression were enriched into toll-like receptor signaling pathway, nod-like receptor signaling pathway, aminoacyl tRNA biosynthetic, glutathione metabolism.

Conclusion

High expression of AKR1B10 mRNA in liver cancer tissues is a risk factor for poor prognosis. Rt-PCR could be used to rapidly detect the expression of AKR1B10 mRNA in liver cancer tissues to evaluate the prognosis of patients, which is a new indicator for predicting the prognosis of patients with hepatocellular carcinoma.

Key words: Carcinoma, hepatocellular, Aldo-keto reductase family1, member B10, Gene expression, The cancer genome atlas, Clinical significance
图1 AKR1B10在肝癌组织和癌旁组织表达对比
图1 AKR1B10表达与370例肝癌患者预后关系[注：有4例肝癌样本中不包含临床参数和生存信息，只有表达量数据，因此此处应是370例]
表1 影响370例肝癌患者预后因素的单因素和多因素分析
变量 单因素分析 多因素分析
HR(95%CI) P值 HR(95%CI) P值
年龄 1.01(0.99～1.02) 0.59 1(0.98～1.02) 0.7
性别 0.78(0.49～1.25) 0.3 0.77(0.44～1.32) 0.337
病理分级 1.02(0.75～1.39) 0.91 1.08(0.76～1.52) 0.678
病理分期 1.86(1.46～2.39) <0.01 1.41(0.54～3.69) 0.48
T分期 1.8(1.43～2.27) <0.01 1.38(0.6～3.22) 0.45
M分期 3.85(1.21～12.28) 0.02 0.81(0.21～3.13) 0.759
N分期 2.02(0.49～8.28) 0.33 1.77(0.23～13.32) 0.58
AKR1B10 1.09(1.01～1.17) 0.02 1.13(1.04～1.22) 0.003
表2 AKR1B10表达与370例肝癌患者临床病理特征的相关性分析
变量 N OR P
分期(III-IV vs. I-II) 353 0.58(0.36～0.95) 0.03
转移(M1 vs. M0) 276 3.05(0.38～62) 0.34
T分期(T3-4 vs. T1-2) 374 0.6(0.38～0.98) 0.04
N分期(N2-3 vs. N0-1) 261 0.33(0.02～2.6) 0.34
分级(g3-4 vs. G1-2) 372 1.05(0.69～1.61) 0.83
图3 GAES分析AKR1B10相关富集基因集[A: Nod样受体信号通路；B: toll样受体信号通路；C:氨基酰tRNA生物合成；D:谷胱甘肽代谢]
[1]
Forner A, Reig M, Bruix J. Hepatocellular carcinoma [J]. Lancet (London, England), 2018, 391(10127): 1301-1314.
[2]
Zheng W, Jiang F, Shan J, et al. Levels of serum IgG subclasses in patients with liver disease: A retrospective study[J]. Exp Ther Med, 2020, 21(1): 45-54.
[3]
Zeng J, Zeng J, Wu Q, et al. Novel inflammation-based prognostic nomograms for individualized prediction in hepatocellular carcinoma after radical resection[J]. Ann Transl Med, 2020, 8(17): 1061.
[4]
Kang S-O, Kwak M-K. Alcohol dehydrogenase 1 and NAD(H)-linked methylglyoxal oxidoreductase reciprocally regulate glutathione-dependent enzyme activities in Candida albicans[J]. J Microbiol, 2021, 59(1): 76-91.
[5]
Fang C-Y, Lin Y-H, Chen C-L. Overexpression of akr1b10 predicts tumor recurrence and short survival in oral squamous cell carcinoma patients[J]. J Oral Pathol Med , 2019, 48(4): 712-719.
[6]
Hung J-J, Yeh Y-C, Hsu W-H. Prognostic significance of akr1b10 in patients with resected lung adenocarcinoma[J]. Thorac Cancer, 2018, 9(11): 1492-1499.
[7]
Ahmed SMU, Jiang ZN, Zheng ZH, et al. AKR1B10 expression predicts response of gastric cancer to neoadjuvant chemotherapy[J]. Oncol Lett, 2019, 17(1): 773-780.
[8]
Ha SY, Song DH, Lee JJ, et al. High expression of aldo-keto reductase 1b10 is an independent predictor of favorable prognosis in patients with hepatocellular carcinoma[J]. Gut Liver, 2014, 8(6): 648-654.
[9]
Wang Y-Y, Qi L-N, Zhong J-H, et al. High expression of AKR1B10 predicts low risk of early tumor recurrence in patients with hepatitis B virus-related hepatocellular carcinoma[J]. Sci Rep, 2017, 7: 42199.
[10]
Jin J, Liao W, Yao W, et al. Aldo-keto reductase family 1 member b 10 mediates liver cancer cell proliferation through sphingosine-1-phosphate[J]. Sci Rep, 2016, 6: 22746.
[11]
Wang J, Zhou Y, Fei X, et al. Biostatistics mining associated method identifies AKR1B10 enhancing hepatocellular carcinoma cell growth and degenerated by miR-383-5p[J]. Sci Rep, 2018, 8(1): 11094.
[12]
Elebo N, Fru P, Omoshoro-Jones J, et al. Role of different immune cells and metabolic pathways in modulating the immune response in pancreatic cancer (Review)[J]. Mol Med Rep, 2020, 22(6): 4981-4991.
[13]
Khayami R, Hashemi SR, Kerachian MA. Role of aldo-keto reductase family 1 member B1 (AKR1B1) in the cancer process and its therapeutic potential[J]. J Cell Mol Med, 2020, 24(16): 8890-8902.
[14]
Taskoparan B, Seza EG, Demirkol S, et al. Opposing roles of the aldo-keto reductases AKR1B1 and AKR1B10 in colorectal cancer[J]. Cell Oncol (Dordr), 2017, 40(6): 563-578.
[15]
Yao Y, Wang X, Zhou D, et al. Loss of AKR1B10 promotes colorectal cancer cells proliferation and migration via regulating FGF1-dependent pathway[J]. Aging (Albany NY), 2020, 12(13): 13059-13075.
[16]
Li J, Guo Y, Duan L, et al. AKR1B10 promotes breast cancer cell migration and invasion via activation of ERK signaling[J]. Oncotarget, 2017, 8(20): 33694-33703.
[17]
Zu X, Yan R, Pan J, et al. Aldo-keto reductase 1B10 protects human colon cells from DNA damage induced by electrophilic carbonyl compounds[J]. Mol Carcinog, 2017, 56(1): 118-129.
[18]
Liu F-Y, Fang B-Q, Sun L-M, et al. The Role of the NOD1/Rip2 Signaling Pathway in Myocardial Remodeling in Spontaneously Hypertensive Rats[J]. Med Sci Monit, 2020, 26: e924748.
[19]
Udden SMN, Peng L, Gan J-L, et al. Nod2 suppresses colorectal tumorigenesis via downregulation of the tlr pathways[J]. Cell Rep, 201, 19(13): 2756-2770.
[20]
Ayala-Cuellar AP, Cho J, Choi K-C. Toll-like receptors: A pathway alluding to cancer control[J]. J Cell Physiol, 2019, 234(12): 21707-21715.
[21]
Hyeon DY, Kim JH, Ahn TJ, et al. Evolution of the multi-tRNA synthetase complex and its role in cancer[J]. J Biol Chem, 2019, 294(14): 5340-5351.
[22]
Xu Y, Zheng X, Bai X, et al. Simultaneous integrated boost intensity-modulated radiotherapy for locally advanced non-small cell lung cancer in chinese population: A retrospective study[J]. Oncotarget, 2017, 8(30): 49084-49092.
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