基于TCGA数据库分析非小细胞肺癌SERPINA1、FHIT甲基化水平及临床意义

doi:10.16138/j.1673-6087.2021.02.008

摘要/Abstract

摘要：

目的：基于TCGA数据库的肺腺癌、肺鳞癌临床数据及甲基化数据,分析非小细胞肺癌（non-small cell lung cancer, NSCLC）患者丝氨酸蛋白酶抑制剂家族A成员1（serine protease inhibitor A1, SERPINA1）、脆性组氨酸三联体（fragile histidine triad,FHIT）基因的甲基化特征。方法：通过TCGA数据库在线和下载分析肺腺癌、肺鳞癌的临床数据和肿瘤组织SERPINA1、FHIT基因的mRNA和甲基化数据,探讨SERPINA1、FHIT甲基化与患者临床病理特征的相关性。结果：肺腺癌和肺鳞癌中的SERPINA1表达水平均低于癌旁对照组织。男性肺腺癌患者肿瘤组织SERPINA1甲基化水平低于女性腺癌患者（P<0.05）。有转移的肺腺癌患者的癌组织SERPINA1较无转移的肺腺癌患者呈低甲基化（P<0.05）。未发现SERPINA1、FHIT甲基化与吸烟史、TNM分期和总生存期存在相关性。结论：SERPINA1和FHIT甲基化可能参与肺癌发生、发展,NSCLC患者SERPINA1低甲基化与肿瘤转移相关。

关键词: 非小细胞肺癌, 表观遗传学, 甲基化, 丝氨酸蛋白酶抑制剂, 脆性组氨酸三联体, 吸烟

Abstract:

Objective To investigate the significance of serine protease inhibitor A1 (SERPINA1) and fragile histidine triad(FHIT) methylation in non-small cell lung cancer(NSCLC) patients based on analysis of TCGA database. Methods The information of SERPINA1/FHIT gene expression, methylation information and associated clinical manifestations were retrieved from TCGA database and analyzed both online and offline. The link between the magnitude of SERPINA1 and FHIT methylation and parameters, such as age, gender, histological-type, smoking history and TNM stage, was probed. Results The expression level of SERPINA1 was higher in tumor tissues other than adjacent non-tumor lung tissues in both lung adenocarcinoma (LUAD) and lung squamous-cell cancer (LUSC) (P<0.05). Hypomethylation of SERPINA1 was mostly observed in LUAD tissue of male patients or individuals with metastasis(P<0.05). The methylation of SERPINA1 and FHIT methylation was not affected by smoking history, nor was it associated with TNM stage or overall survival. Conclusions SERPINA1 and FHIT methylation might play a role in lung cancer. Hypomethylation in SERPINA1 is related with metastasis of LUAD.

Key words: Non-small cell lung cancer, Epigenetic, Methylation, Serine protease inhibitor A1, Fragile histidine triad, Cigarette smoking

中图分类号:

R743.2

王佳卉, 李宁, 孙娴雯, 林莹妮, 丁永杰, 宋鹤杰, 李庆云. 基于TCGA数据库分析非小细胞肺癌SERPINA1、FHIT甲基化水平及临床意义[J]. 内科理论与实践, 2021, 16(02): 103-107.

WANG Jiahui, LI Ning, SUN Xianwen, LIN Yingni, DING Yongjie, SONG Hejie, LI Qingyun. The magnitude and clinical implication of SERPINA1 and FHIT methylation in non-small cell lung cancer based on analysis of TCGA database[J]. Journal of Internal Medicine Concepts & Practice, 2021, 16(02): 103-107.

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项目	肺腺癌		肺鳞癌
项目	SERPINA1（n=458）	FHIT（n=458）	SERPINA1（n=370）	FHIT（n=74）
年龄(岁)	65.12±10.15		67.58±8.73	69.31±8.91
性别[n(%)]
男性	214(46.72)		274(74.05)	52(70.27)
女性	244(53.28)		96(25.95)	22(29.73)
吸烟史[n(%)]	322(70.31)		319(86.22)	59(79.73)
是否死亡（否/是）	293/165		210/160	33/41
人种（白色人种/其他）	353/105		274/96	58/16
TNM分期[n(%)]
Ⅰ~Ⅱ期	364(79.48)		309(83.51)	61(82.43)
Ⅲ期	74(16.16)		57(15.40)	12(16.22)
Ⅳ期	20(4.37)		4(1.08)	1(1.35)