Please wait a minute...
浙江大学学报(医学版)  2021, Vol. 50 Issue (1): 90-96    DOI: 10.3724/zdxbyxb-2021-0052
原著     
异嗜性和多变性逆转录病毒受体 1在乳头状甲状腺癌患者中表达的意义
邹华伟1(),项承2,*()
1. 河南省周口市中心医院甲状腺乳腺外科,河南 周口 466000
2. 浙江大学医学院附属第二医院甲状腺外科,浙江 杭州 310009
Clinical implication of xenotropic and polytropic retrovirus receptor 1 in papillary thyroid carcinoma
ZOU Huawei1(),XIANG Cheng2,*()
1. Department of Thyroid and Breast Surgery,Zhoukou Central Hospital,Zhoukou 466000,Henan Province,China;
2. Department of Thyroid Surgery,the Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310009,China
 全文: PDF(3459 KB)   HTML( 12 )
摘要:

目的:探索异嗜性和多变性逆转录病毒受体1( XPR1)基因在乳头状甲状腺癌(PTC)患者中表达的价值及其参与PTC发生发展的潜在通路。 方法:通过HPA数据库和UALCAN数据库探索XPR1在PTC组织及正常组织中的表达水平;通过cBioPortal数据库获取PTC患者临床资料及 XPR1基因表达值,探索 XPR1表达水平与患者性别、年龄、PTC分型、T分期、N分期、M分期和疾病分期的相关性;Cox回归分析探索PTC患者预后的影响因素;利用cBioPortal数据库探索 XPR1基因组学改变;基因本体(GO)和京都基因与基因组百科全书(KEGG)分析探索 XPR1参与PTC的生物学途径。 结果:HPA数据库分析发现,与正常组织相比,XPR1在PTC组织中表达增加;UALCAN数据库分析发现, XPR1基因表达量在PTC组织中较正常组织明显增多( P<0.01),其中高柱亚型表达量最高,滤泡亚型表达量最低。PTC患者的 XPR1基因表达水平与患者年龄、PTC分型、T分期、N分期和疾病分期相关( P<0.05或 P<0.01),而与性别和M分期不相关(均 P>0.05)。回归分析结果显示, XPR1表达水平可作为PTC患者预后的独立影响因子( HR=2.894, P<0.05)。cBioPortal数据库显示,6%的PTC患者出现 XPR1基因突变,主要表现为错义突变,突变位点为蛋白结构域E615K。富集分析结果显示, XPR1可能通过参与调节代谢通路影响PTC发生发展。 结论: XPR1在PTC组织中表达增加,且影响患者预后,可能通过参与代谢通路影响PTC的发生发展,可作为PTC诊断和治疗的潜在靶点。

关键词: 乳头状甲状腺癌异嗜性和多变性逆转录病毒受体1预后富集分析生物信息学分析    
Abstract:

Objective:To investigate the expression of xenotropic and polytropic retrovirus receptor 1 ( XPR1) in papillary thyroid cancer (PTC) and its clinical implication. Methods: The HPA and UALCAN databases were used to explore the expression of XPR1 in PTC and normal tissues. The cBioPortal database was used to obtain the clinical data of PTC patients and XPR1 gene expression profile. The correlation of XPR1 expression with gender,age,sub-types,T stage,N stage,M stage and clinical stage of patients were analyzed. Cox regression was conducted to analysis the factors affecting the prognosis of PTC patients. The mutation of XPR1 was assessed through cBioPortal database. GO and KEGG analyses were used to explore the related biological pathway of XPR1 involved in PTC. Results: HPA database analysis showed that XPR1 was highly expressed in PTC tissue compared with normal tissues. UALCAN analysis displayed that XPR1 expression was significantly higher in PTC tissue compared with normal tissues ( P<0.01),and the highest and lowest expressions of XPR1 were observed in tall cell and follicular sub-type of PTC,respectively. The expression of XPR1 was correlated with age,sub-types,T stage,N stage and disease stage of PTC patients ( P<0.05 or P<0.01),but was not correlated with gender and M stage (all P>0.05). Cox regression analysis showed that XPR1 was an independent prognostic factor of PTC patients ( HR=2.894, P<0.05). The cBioPortal database indicated that the XPR1mutation appeared in 6% PTC patients; the mutation type mainly was missense and the mutation point was located at the E615K. Enrichment analysis indicated that XPR1 might affect the PTC progression through involvement in metabolic pathway. Conclusions: XPR1 is highly expressed in PTC tissues,which is associated with the prognosis of patients. Metabolic pathway associated with XPR1 might play an important role in PTC progression,indicating that XPR1 might be a novel biomarker for diagnosis and treatment of PTC.

Key words: Papillary thyroid carcinoma    Xenotropic and polytropic retrovirus receptor 1    Prognosis    Enrichment analysis    Bioinformatics
收稿日期: 2020-11-10 出版日期: 2021-05-16
CLC:  R736.1  
通讯作者: 项承     E-mail: zouhuawei2006@163.com;chengxiang@zju.edu.cn
作者简介: 邹华伟,副主任医师,主要从事甲状腺乳腺外科学研究;E-mail:zouhuawei2006@163.com;https://orcid.org/ 0000-0003-1527-8788
服务  
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章  
邹华伟
项承

引用本文:

邹华伟,项承. 异嗜性和多变性逆转录病毒受体 1在乳头状甲状腺癌患者中表达的意义[J]. 浙江大学学报(医学版), 2021, 50(1): 90-96.

ZOU Huawei,XIANG Cheng. Clinical implication of xenotropic and polytropic retrovirus receptor 1 in papillary thyroid carcinoma. J Zhejiang Univ (Med Sci), 2021, 50(1): 90-96.

链接本文:

http://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2021-0052        http://www.zjujournals.com/med/CN/Y2021/V50/I1/90

图 1  XPR1在PTC组织及正常组织中的表达 A:正常甲状腺组织和PTC组织免疫荧光染色检测XPR1蛋白表达结果. 正常甲状腺组织着色程度和荧光强度中等,而PTC组织着色程度高,荧光强度强. B:不同亚型PTC组织中基因表达比较. 与正常甲状腺组织比较,<0.01;与滤泡亚型比较,< 0.01. PTC:乳头状甲状腺癌;XPR1:异嗜性和多变性逆转录病毒受体1.

临床特征

n

XPR1表达(秩均值)

U2

年龄

?

<55岁

285

178.03

9697.00 *

?

≥55岁

79

165.87

性别

?

93

185.99

12277.00

271

181.30

PTC分型

?

经典亚型

249

200.36

74.82 **

滤泡亚型

81

94.26

高柱亚型

28

240.57

T分期

?

T1

106

159.49

10.98 *

T2

125

177.11

T3

119

201.97

T4

12

218.67

N分期

?

N0

172

133.70

8119.00 **

N1

153

195.93

M分期

?

M0

193

100.36

510.00

M1

6

88.50

疾病分期

?

209

183.88

14.45 **

41

125.95

77

194.38

35

204.06

表 1  不同临床特征PTC患者表达水平比较

特征

单因素分析

多因素分析

相对危险度

95%可信区间

P

相对危险度

95%可信区间

P

年龄

1.203

0.582~4.033

>0.05

4.112

0.802~21.083

>0.05

性别

2.070

0.735~5.825

>0.05

1.170

0.063~21.801

>0.05

XPR1表达

2.850

1.068~7.609

<0.05

2.894

1.078~7.764

<0.05

原发病灶

1.251

0.721~2.167

>0.05

3.235

0.982~6.742

>0.05

T分期

1.390

0.921~2.100

>0.05

0.733

0.305~1.763

>0.05

N分期

2.121

1.167~3.853

<0.05

2.136

1.173~7.764

<0.05

M分期

1.276

0.532~3.064

>0.05

1.417

0.029~68.739

>0.05

危险类群 *

0.415

0.182~0.947

<0.05

1.662

0.107~25.728

>0.05

表 2  PTC患者预后相关因素回归分析结果
图 2  与共表达基因功能富集分析结果 XPR1仅显示前6位分析条目. XPR1:异嗜性和多变性逆转录病毒受体1.

KEGG通路编号和名称

数量

P

相关基因

hsa01100:代谢通路

34

<0.01

GCDH、SGMS1、TUSC3、NDUFB2、SAT2、SGMS2、SDSL、HSD17B8、PAPSS1、CYP17A1、NFS1、NT5E、POLD2、IDH3B、INPP5J、IDS、CYC1、ACSS1、ACADS、COX8A、GALNT5、PDHA1、MMAB、DCXR、CSGALNACT2、MBOAT2、COQ5、NT5C3B、BDH1、CYP2S1、RGN、SUCLG1、BCAT2、PIGH

hsa01200:碳水化合物代谢

7

<0.01

PDHA1、RGN、IDH3B、SUCLG1、ACSS1、SDSL、ACADS

hsa01130:抗生素合成

9

<0.05

GCDH、PDHA1、RGN、IDH3B、SUCLG1、ACSS1、SDSL、PAPSS1、BCAT2

hsa04060:细胞因子连接受体

9

<0.05

ACGCVR1、FAS、TNFSF11、TNFRSF10A、IL1RAP、INHBA、OSMR、IL18R1、IL13RA1

表 3  共表达基因KEGG功能富集结果
1 ANTONELLI A, LA MOTTA C . Novel therapeutic clues in thyroid carcinomas:the role of targeting cancer stem cells[J]. Med Res Rev, 2017, 37(6): 1299-1317.
doi: 10.1002/med.21448
2 FALLAHI P, FERRARI S M, GALDIERO M R, et al. Molecular targets of tyrosine kinase inhibitors in thyroid cancer[J]. Seminars Cancer Biol, 2020.,
doi: 10.1016/j.semcancer.2020.11.013
3 CABANILLAS M E, MCFADDEN D G, DURANTE C . Thyroid cancer[J]. Lancet, 2016, 388(10061): 2783-2795.
doi: 10.1016/S0140-6736(16)30172-6
4 DURANTE C, MONTESANO T, TORLONTANO M, et al. Papillary thyroid cancer:time course of recurrences during postsurgery surveillance[J]. J Clin Endocrinol Metab, 2013, 98(2): 636-642.
doi: 10.1210/jc.2012-3401
5 RAMOS E M,OLIVEIRA J,SOBRIDO M J,et al. Primary familial brain calcification[M]//ADAM M P,ARDINGER H H,PAGON R A,et al. GeneReviews?. Seattle (WA):University of Washington,1993–2021 .
6 LEGATI A, GIOVANNINI D, NICOLAS G, et al. Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export[J]. Nat Genet, 2015, 47(6): 579-581.
doi: 10.1038/ng.3289
7 ANHEIM M, LóPEZ-SáNCHEZ U, GIOVANNINI D, et al. XPR1 mutations are a rare cause of primary familial brain calcification[J]. J Neurol, 2016, 263(8): 1559-1564.
doi: 10.1007/s00415-016-8166-4
8 LI X, GU C, HOSTACHY S, et al. Control of XPR1-dependent cellular phosphate efflux by InsP 8 is an exemplar for functionally-exclusive inositol pyrophosphate signaling[J] . Proc Natl Acad Sci USA, 2020, 117(7): 3568-3574.
doi: 10.1073/pnas.1908830117
9 VAUGHAN A E, MENDOZA R, ARANDA R, et al. Xpr1 is an atypical G-protein-coupled receptor that mediates xenotropic and polytropic murine retrovirus neurotoxicity[J]. J Virol, 2012, 86(3): 1661-1669.
doi: 10.1128/JVI.06073-11
10 YAO X P, ZHAO M, WANG C, et al. Analysis of gene expression and functional characterization of XPR1:a pathogenic gene for primary familial brain calcification[J]. Cell Tissue Res, 2017, 370(2): 267-273.
doi: 10.1007/s00441-017-2663-3
11 CHEN W C, LI Q L, PAN Q, et al. Xenotropic and polytropic retrovirus receptor 1 (XPR1) promotes progression of tongue squamous cell carcinoma (TSCC) via activation of NF-κB signaling[J]. J Exp Clin Cancer Res, 2019, 38(1): 167.
doi: 10.1186/s13046-019-1155-6
12 BREYER J P, MCREYNOLDS K M, YASPAN B L, et al. Genetic variants and prostate cancer risk:candidate replication and exploration of viral restriction genes[J]. Cancer Epidemiol Biomarkers Prev, 2009, 18(7): 2137-2144.
doi: 10.1158/1055-9965.EPI-08-1223
13 陈平圣,冯振卿,刘慧. 病理学[M]. 南京:东南大学出版社,2017:110–117.CHEN Pingsheng,FENG Zhenqing,LIU Hui. Pathology[M]. Nanjing: Southeast University Press,2017: 110–117. (in Chinese) .
14 KIM M, KIM W G, OH H S, et al. Comparison of the seventh and eighth editions of the American Joint Committee on Cancer/Union for international cancer control tumor-node-metastasis staging system for differentiated thyroid cancer[J]. Thyroid, 2017, 27(9): 1149-1155.
doi: 10.1089/thy.2017.0050
15 李树春,董慧蕾,李振东.分化型甲状腺癌危险组的划分及其意义[J]. 中国耳鼻咽喉头颈外科,2006,41(9):611–614. DOI:10.3969/j.issn.1672-7002.2006.09.008 .
16 RAMOS E M, CARECCHIO M, LEMOS R, et al. Primary brain calcification:an international study reporting novel variants and associated phenotypes[J]. Eur J Hum Genet, 2018, 26(10): 1462-1477.
doi: 10.1038/s41431-018-0185-4
[1] 李占鲁,黄翯,张文斌,王敏,傅国胜. 冠状动脉CT血管造影提示临界病变有易损斑块患者预后分析[J]. 浙江大学学报(医学版), 2020, 49(1): 76-81.
[2] 米爽,吴燕君,洪正华,王章富,冯兴兵,郑光彬. TLR4/MyD88/NF-κB通路基因及相关炎症因子在继发性脊髓损伤患者中的表达[J]. 浙江大学学报(医学版), 2019, 48(6): 609-616.
[3] 王雅芸,陈原,杨蒙蒙,习芳芳,占琪涛,蒋颖,赵柏惠,罗琼. 淋巴水囊瘤或颈部组织增厚胎儿预后分析[J]. 浙江大学学报(医学版), 2019, 48(4): 434-438.
[4] 童凡,杨茹莱,刘畅,吴鼎文,张婷,黄新文,洪芳,钱古柃,黄晓磊,周雪莲,舒强,赵正言. 新生儿酪氨酸血症筛查及基因谱分析[J]. 浙江大学学报(医学版), 2019, 48(4): 459-464.
[5] 钟晚思, 陈智才, 陈红芳, 徐冬娟, 王志敏, 胡海芳, 吴承龙, 张晓玲, 马小董, 王亚仙, 胡海涛, 楼敏, 浙江省缺血性脑卒中静脉溶栓的临床行为干预研究协作组 . 院前急救医疗服务对缺血性脑卒中患者静脉溶栓预后的影响[J]. 浙江大学学报(医学版), 2019, 48(3): 241-246.
[6] 陈红芳, 龚筱弦, 徐冬娟, 王志敏, 胡海芳, 吴承龙, 张晓玲, 马小董, 王亚仙, 胡海涛, 楼敏, 陈智才, 浙江省缺血性脑卒中静脉溶栓的临床行为干预研究协作组 . 治疗时间提前可改善缺血性脑卒中患者再灌注治疗的预后[J]. 浙江大学学报(医学版), 2019, 48(3): 247-253.
[7] 张聪聪, 楼敏, 陈智才, 陈红芳, 徐冬娟, 王志敏, 胡海芳, 吴承龙, 张晓玲, 马小董, 王亚仙, 胡海涛, 浙江省缺血性脑卒中静脉溶栓的临床行为干预研究协作组 . 医院内缺血性脑卒中患者静脉溶栓时间及预后分析[J]. 浙江大学学报(医学版), 2019, 48(3): 260-266.
[8] 泮飞虎, 楼敏, 陈智才, 陈红芳, 徐冬娟, 王志敏, 胡海芳, 吴承龙, 张晓玲, 马小董, 王亚仙, 胡海涛, 浙江省缺血性脑卒中静脉溶栓的临床行为干预研究协作组 . 不同工作时间段就诊对缺血性脑卒中患者静脉溶栓预后的影响[J]. 浙江大学学报(医学版), 2019, 48(3): 267-274.
[9] 杜东芬,朱丽霞,王云贵,叶琇锦. 肾母细胞瘤1基因表达及其对急性髓系白血病患者预后的预测价值[J]. 浙江大学学报(医学版), 2019, 48(1): 50-57.
[10] 陈倩,刘露,张静静,韩赛,崔保霞,张友忠,孔北华. 237例宫颈腺癌及腺鳞癌患者临床特征及预后分析[J]. 浙江大学学报(医学版), 2018, 47(4): 357-361.
[11] 蒋滟蕲,杨雅兰,杨婷,李玥伶,陈莉玲,燕锦,杨艳芳. UCP2 rs659366位点多态性与结直肠癌术后患者生存结局的关系[J]. 浙江大学学报(医学版), 2018, 47(2): 143-149.
[12] 丁元,孙忠权,章文燕,章向英,姜源聪,严盛,王伟林. 腹腔镜胰体尾切除术患者围手术期加速康复管理及效果评估[J]. 浙江大学学报(医学版), 2017, 46(6): 625-629.
[13] 潘瑶 等. 胰腺癌的影像学精准诊断与评估[J]. 浙江大学学报(医学版), 2017, 46(5): 462-467.
[14] 潘静颖 等. PET-CT与乳腺癌分子病理分型、治疗反应及预后的相关性研究进展[J]. 浙江大学学报(医学版), 2017, 46(5): 473-480.
[15] 李爱静 等. 动态增强磁共振成像参照物模型定量参数与乳腺癌预后因素及分子病理分型的关系[J]. 浙江大学学报(医学版), 2017, 46(5): 505-510.