[1]刘雪梅,沈 娜.TIMP-2基因418 C>G位点多态性与非小细胞肺癌易感性的相关性研究[J].现代检验医学杂志,2025,40(02):41-46.[doi:10.3969/j.issn.1671-7414.2025.02.008]
　LIU Xuemei,SHEN Na.Study on the Correlation between Polymorphism of TIMP-2 Gene 418 C>G Locus and Susceptibility to NSCLC[J].Journal of Modern Laboratory Medicine,2025,40(02):41-46.[doi:10.3969/j.issn.1671-7414.2025.02.008]
点击复制

TIMP-2基因418 C>G位点多态性与非小细胞肺癌易感性的相关性研究()
分享到：

《现代检验医学杂志》[ISSN:/CN:]

卷:
第40卷
期数:
2025年02期
页码:
41-46
栏目:
论著
出版日期:
2025-03-15

文章信息/Info

Title:
Study on the Correlation between Polymorphism of TIMP-2 Gene 418 C>G Locus and Susceptibility to NSCLC
文章编号:
1671-7414（2025）02-041-06
作者:
刘雪梅; 沈 娜
（遂宁市中心医院肿瘤内科，四川遂宁 629000）
Author(s):
LIU Xuemei; SHEN Na
（Department of Oncology，Suining Central Hospital，Sichuan Suining 629000，China）
关键词:
组织金属蛋白酶抑制剂-2 基因; 基因多态性; 非小细胞肺癌; 易感性
分类号:
R734.2；R730.43
DOI:
10.3969/j.issn.1671-7414.2025.02.008
文献标志码:
A
摘要:
目的 探讨组织金属蛋白酶抑制剂-2（TIMP-2）基因418 C>G 位点多态性与非小细胞肺癌（NSCLC）易感性的关系。方法 选择2021 年5 月～ 2023 年5 月于遂宁市中心医院收治的167 例NSCLC 患者作为观察组，选择同期于该院进行体检的183 例健康者作为对照组。比较两组的一般资料及分析TIMP-2 基因多态性。检测并比较两组TIMP-2 基因多态性位点基因型及等位基因频率分布。再通过Logistic 回归分析TIMP-2 基因418 C>G 位点与NSCLC 的相关性。结果 观察组的BMI ≥ 24kg/m2 占比（67.07%）和吸烟人数占比（61.08%）高于对照组（44.26% 和40.44%），差异具有统计学意义（χ2=18.356，14.881，均P ＜ 0.001）。变异型GG 纯合子产生的3 个长度为230bp，51bp 和23bp 的片段，野生型CC 纯合子产生长度为253bp 和51bp 的片段，杂合子GC 产生的4 个长度为253bp，230bp，51bp 和23bp 的片段，其中51bp 和23bp 片段不显示，TIMP-2 418 C>G 基因一致性为100%。基因分型频率满足Hardy-Weinberg 遗传平衡（P>0.05）。观察组TIMP-2 基因型CC，GC，GG 基因频率分别为10.18%，41.92% 和47.90%，对照组分别为4.37%，37.70% 和57.92%，差异具有统计学意义（χ2=6.163，P=0.046）。观察组TIMP-2 等位基因C，G 频率分别为31.14%，68.86%，对照组分别为23.22%，76.78%，差异具有统计学意义（χ2=5.549，P=0.018）。与对照组比较，Logistic 回归分析发现携带C 等位基因明显增加人群患NSCLC 的发病风险（OR=2.669，95%CI：1.478 ～ 2.936，P<0.01）；与GG+GC 型组相比，CC 型基因患者的染色体核型预后不良占比、国际预后积分系统（IPSS）危险分组中高危占比、C 反应蛋白（CRP）以及降钙素原（PCT）水平升高，差异具有统计学意义（t/χ2=3.633 ～ 11.249，均P <0.001）；中性粒细胞绝对计数（ANC）、血红蛋白（HGB）、血小板（PLT）水平降低，差异具有统计学意义（t=4.760，2.015，2.212，均P <0.05）。多因素COX 回归分析结果显示，CC 型基因、染色体核型、IPSS 危险分组、ANC，HGB，PLT，CRP，PCT 均为NSCLC 患者预后不良的危险因素（Wald χ2=3.072 ～ 17.611，均P<0.05）。多因子降维法（MDR）结果显示，对于NSCLC 发生风险，具有ANC，HGB，PLT，CRP 以及PCT 水平异常和TIMP-2 基因多态性交互组合人群是非上述组合人群的2.650 倍。结论 TIMP-2 基因418 C>G 位点的CC 基因型和C 等位基因携带与NSCLC 的发病风险有显著相关性，是NSCLC 的独立危险因素。
Abstract:
Objective To investigate the relationship between 418 C>G polymorphism of tissue metalloproteinase inhibitor-2 (TIMP-2) gene and susceptibility to non-small cell lung cancer（NSCLC）. Methods A total of 167 patients with NSCLC admitted to Suining Central Hospital from May 2021 to May 2023 were selected as the observation group, and 183 healthy subjects who underwent physical examination in the hospital during the same period were selected as the control group. The general data of the two groups were compared and the polymorphism of the TIMP-2 gene was analyzed. The genotype and allele frequency distribution of the polymorphic locus of the TIMP-2 gene were detected and compared between the two groups. Logistic regression was used to analyze the correlation between TIMP-2 gene 418 C>G site and NSCLC. Results The proportion of BMI ≥ 24kg/m2 and smoking in the observation group were 67.07% and 61.08%， respectively, which were 44.26% and 40.44% in the control group, and the differences were statistically significant (χ2=18.356，14.881, all P < 0.001). The variant GG homozygote produced three fragments of 230bp, 51bp and 23bp in length, the wild-type CC homozygote produced 253bp and 51bp in length, and the heterozygous GC produced four pieces of 253bp, 230bp, 51bp and 23bp in length. The 51bp and 23bp fragments were not shown, and the TIMP-2 418 C>G gene identity was 100%. The genotype frequencies met the Hardy-Weinberg genetic equilibrium (P>0.05). The frequencies of CC, GC and GG of the TIMP-2 genotype in the observation group were 10.18%, 41.92% and 47.90%, respectively, and those in the control group were 4.37%, 37.70% and 57.92%, respectively, and the difference was statistically significant (χ2=6.163，P=0.046). The frequencies of the C and G alleles of TIMP-2 in the observation group were 31.14% and 68.86%, respectively, and those in the control group were 23.22% and 76.78%, respectively, and the difference was statistically significant (χ2=5.549, P=0.018).Compared with the control group Logistic regression analysis showed that genotype carrying the C allele significantly increased the risk of NSCLC (OR=2.669, 95%CI: 1.478 ～ 2.936, P<0.01). Compared with the GG+GC group, the proportion of patients with CC genotype who had poor chromosome karyotype prognosis, the proportion of high-risk group in the International Prognostic Scoring System (IPSS) risk group and the levels of CRP and PCT were increased, and the differences were statistically significant (t=3.633 ～ 11.249, all P <0.001). Absolute neutrophil count (ANC)，Haemoglobin (HGB) and Platelet (PLT) decreased, and the differences were statistically significant (t=4.760, 2.015, 2.212，all P <0.05). Multivariate COX regression analysis showed that CC genotype， chromosome karyotype， IPSS risk group， ANC, HGB, PLT, CRP, and PCT were risk factors for poor prognosis in NSCLC (Wald χ2=3.072 ～ 17.611, all P<0.05). The results of the multifactor dimensionality reduction (MDR) method showed that the interaction combination of abnormal ANC, HGB, PLT, CRP, and PCT levels and TIMP-2 gene polymorphism was 2.650 times higher than that of NSCLC. Conclusion The CC genotype and C allele of the 418 C>G locus of TIMP-2 gene are significantly associated with the risk of NSCLC and are independent risk factors for NSCLC.

参考文献/References:

[1] STRAVOPODIS D J, PAPAVASSILIOU K A, PAPAVASSILIOU A G. Vistas in non-small cell lung cancer (NSCLC) treatment of kinome and signaling networks[J]. International Journal of Biological Sciences, 2023, 19(7): 2002-2005.
[2] MIYABE S, ITO S, SATO I, et al. Clinical and genomic features of non-small cell lung cancer occurring in families[J]. Thoracic Cancer, 2023, 14(10): 940-952.
[3] WANG Xinan, ROMERO-GUTIERREZ C W, KOTHARI J, et al. Prediagnosis smoking cessation and overall survival among patients with non-small cell lung cancer[J]. JAMA Network Open, 2023, 6(5): e2311966.
[4] PEREIRA E EB, MODESTO A AC, FERNANDES B M, et al. Association between polymorphism of genes IL-1A,NFKB1,PAR1,TP53,and UCP2 and susceptibility to non-small cell lung cancer in the Brazilian Amazon[J]. Genes(Base1), 2023, 14(2): 461.
[5] 李卫玲, 金笑平, 虞丹, 等.TIMP-2 基因-418G/C 多态性与房颤性脑梗死的关系研究[J].中华全科医学,2022,20(3):411-414. LI Weiling, JIN Xiaoping, YU Dan, et al. Association between matrix metalloproteinase inhibitor-2 gene-418G/C polymorphisms and cerebral infarction with atrial fibrillation[J].Chinese Journal of General Practice, 2022, 20(3): 411-414.
[6] WU Peiliang, LING Xiao, KANG E Y, et al. Effects of TIMP-2 polymorphisms on retinopathy of prematurity risk,severity,recurrence,and treatment response[J]. International Journal of Molecular Sciences, 2022, 23(22): 14199.
[7] 刘捷, 杨玲玲, 程秋霞, 等.NSCLC 患者血清miR-873和miR-138-5p 表达水平及其与免疫微环境及预后的相关性分析[J]. 现代检验医学杂志,2024,39(1):23-28. LIU Jie, YANG Lingling, CHENG Qiuxia, et al. Analysis of the relationship between serum miR-873 and miR-138-5p expression and immune microenvironment and prognosis in patients with nonsmall cell lung cancer[J]. Journal of Modern Laboratory Medicine, 2024, 39(1): 23-28.
[8] 白建云, 张菁, 刘小静.E-cad,TIMP-2 及OPN 对甲状腺癌患者病情进展及预后的价值[J]. 分子诊断与治疗杂志,2022,14(9):1536-1540. BAI Jianyun, ZHANG Jing, LIU Xiaojing. The value of E-cad ,TIMP-2 and OPN on disease progression and prognosis in patients with thyroid cancer[J]. Journal of Molecular Diagnosis and Therapy, 2022, 14(9): 1536-1540.
[9] CAO Chao, XU Ning, ZHENG Xiaoxia, et al. Elevated expression of MMP-2 and TIMP-2 cooperatively correlates with risk of lung cancer[J]. Oncotarget, 2017, 8(46): 80560-80567.
[10] XUE Aiying, FENG Guoxing, ZHU Changchun, et al. Prokaryotic expression,purification and characterization of tissue inhibitor of metalloproteinase-2[J]. Chinese Journal of Biotechnology, 2020, 36(12): 2868-2876.
[11] BARAB?S L, HRITZ I, ISTV?N G, et al. The behavior of MMP-2, MMP-7, MMP-9, and their inhibitors TIMP-1 and TIMP-2 in Adenoma-Colorectal cancer sequence[J]. Digestive Diseases (Basel, Switzerland), 2021, 39(3): 217-224.
[12] BAJBOUJ K, RAMAKRISHNAN R K, ALKETBI H, et al. Targeting KDM4B attenuates IL-13-mediated fibrosis in bronchial fibroblasts of severe asthmatics[J]. Advances in Biomedical and Health Sciences, 2023, 2(1): 13.
[13] SINGH H O, JADHAV S, SAMANI D, et al. Tissue inhibitor of metalloproteinase-2 polymorphisms and risk for HIV-associated neurocognitive disorder [J].Mediators of Inflammation, 2019, 2019: 8278095.
[14] WU Peiliang, LING Xiaochun, KANG E Y C, et al. Effects of TIMP-2 polymorphisms on retinopathy of prematurity risk, severity, recurrence, and treatment response[J]. International Journal of Molecular Sciences, 2022, 23(22): 14199.
[15] KUTLUEV M M, SAFIULLIN R I. Our experience of holmium laser enucleation of the prostate[J]. Urologiia(Moscow, Russia : 1999), 2022(1): 67-71.
[16] KRISTIAN KUR D, TH?GERSEN D, KJELDSEN L, et al. The HemoScreen hematology point-of-care device is suitable for rapid evaluation of acute leukemia patients[J]. International Journal of Laboratory Hematology, 2021, 43(1): 52-60.

相似文献/References:

[1]陈晓露.白细胞介素4基因多态性与结直肠癌的易感性[J].现代检验医学杂志,2015,30(05):105.[doi:10.3969/j.issn.1671-7414.2015.05.032]
　CHEN Xiao-lu.Interleukin-4 Gene Polymorphisms and Colorectal Cancer Susceptibility[J].Journal of Modern Laboratory Medicine,2015,30(02):105.[doi:10.3969/j.issn.1671-7414.2015.05.032]
[2]朱琴芳,丁倩倩,俞钱,等.CD40-1C/T基因多态性与系统性红斑狼疮的相关性研究[J].现代检验医学杂志,2015,30(06):46.[doi:10.3969/j.issn.1671-7414.2015.06.013]
　ZHU Qin-fang,DING Qian-qian,YU Qian,et al.Association of CD40 Gene Polymorphism with the Systemic Lupus Erythematosus[J].Journal of Modern Laboratory Medicine,2015,30(02):46.[doi:10.3969/j.issn.1671-7414.2015.06.013]
[3]黄生金,郑利平,陆俊佳,等.广西地区壮族和汉族冠心病患者胱抑素C水平及其基因多态性的比较研究[J].现代检验医学杂志,2017,32(03):26.[doi:10.3969/j.issn.1671-7414.2017.03.007]
　HUANG Sheng-jin,ZHENG Li-ping,LU Jun-jia,et al.Comparative Study of Cystatin C and Its Gene Polymorphism of Pati ents with Coronary Heart Disease between Zhuang and Han in Guangxi Region[J].Journal of Modern Laboratory Medicine,2017,32(02):26.[doi:10.3969/j.issn.1671-7414.2017.03.007]
[4]曹云,周晓,张晓艳,等.陕西省延安地区育龄女性MTHFR基因多态性和国内多地区相关报道比较分析2)[J].现代检验医学杂志,2019,34(01):62.[doi:10.3969/j.issn.1671-7414.2019.01.016]
　CAO Yun,ZHOU Xiao,ZHANG Xiao-yan,et al.Comparative Analysis of MTHFR Gene Polymorphisms in Women of Childbearing Age in Yan’an Area of Shaanxi Province and Related Reports in Many Regions in China[J].Journal of Modern Laboratory Medicine,2019,34(02):62.[doi:10.3969/j.issn.1671-7414.2019.01.016]
[5]滕祥云,王新梦,刘　维,等.中国汉族结直肠癌患者 UGT1A1*28基因多态性分析[J].现代检验医学杂志,2019,34(06):20.[doi:10.3969 ／ j.issn.1671-7414.2019.06.005]
　TENG Xiang-yun,WANG Xin-meng,LIU Wei,et al.Polymorphism of UGT1A1*28 Gene in Han Patients with Colorectal Cancer in China[J].Journal of Modern Laboratory Medicine,2019,34(02):20.[doi:10.3969 ／ j.issn.1671-7414.2019.06.005]
[6]周　琰,王蓓丽,张春燕,等.消化道肿瘤患者MTHFR 基因多态性与5- 氟尿嘧啶化疗不良反应的相关性研究[J].现代检验医学杂志,2020,35(03):1.[doi:10.3969/j.issn.1671-7414.2020.03.001]
　ZHOU Yan,WANG Bei-li,ZHANG Chun-yan,et al.Relationship between MTHFR Gene Polymorphisms and Adverse Events by 5-FU in Gastrointestinal Cancer[J].Journal of Modern Laboratory Medicine,2020,35(02):1.[doi:10.3969/j.issn.1671-7414.2020.03.001]
[7]洪雄新,李观强,杨 辉,等.2 型糖尿病患者ABCA1 R219K 基因多态性分布及其与血脂水平的相关性研究[J].现代检验医学杂志,2020,35(04):14.[doi:10.3969/j.issn.1671-7414.2020.04.004]
　HONG Xiong-xin,LI Guan-qiang,YANG Hui,et al.Study on Distribution of ABCA1 R219K Gene Polymorphism and Its Correlation with Blood Lipid Levels for Type 2 Diabetes Mellitus Patients[J].Journal of Modern Laboratory Medicine,2020,35(02):14.[doi:10.3969/j.issn.1671-7414.2020.04.004]
[8]杨小柯,何柳媚,全湛柔,等.深圳地区人群乙型肝炎病毒携带者HLA-DRB1 等位基因多态性及关联性分析[J].现代检验医学杂志,2020,35(05):5.[doi:10.3969/j.issn.1671-7414.2020.05.002]
　YANG Xiao-ke,HE Liu-mei,QUAN Zhan-rou,et al.Analysis of Allelic Polymorphism and Association of HLA-DRB1 in Hepatitis B Virus Carriers in Shenzhen[J].Journal of Modern Laboratory Medicine,2020,35(02):5.[doi:10.3969/j.issn.1671-7414.2020.05.002]
[9]张姝,罗洁,许琦,等.贵州地区汉族阿尔茨海默症患者CYP2C19 基因多态性及代谢表型分析[J].现代检验医学杂志,2020,35(05):13.[doi:10.3969/j.issn.1671-7414.2020.05.004]
　ZHANG Shu,LUO Jie,XU Qi,et al.Analysis of CYP2C19 Gene Polymorphism and Metabolic Phenotype in Alzheimerdisease Patients of Han Nationality in Guizhou[J].Journal of Modern Laboratory Medicine,2020,35(02):13.[doi:10.3969/j.issn.1671-7414.2020.05.004]
[10]师文涛,白 蓉,黄剑林,等.陕西省延安地区汉族与国内其他地区育龄妇女 MTHFR 基因 C677T 位点基因型和等位基因分布研究[J].现代检验医学杂志,2020,35(06):78.[doi:doi:10.3969/j.issn.1671-7414.2020.06.019]
　SHI Wen-tao,BAI Rong,HUANG Jian-lin,et al.Comparative Study on MTHFR Gene C677T Locus Genotype and AlleleDistribution between Han Nationality and Women of ChildbearingAge in Yan’an Area of Shaanxi Province[J].Journal of Modern Laboratory Medicine,2020,35(02):78.[doi:doi:10.3969/j.issn.1671-7414.2020.06.019]

备注/Memo

备注/Memo:
作者简介：刘雪梅（1990-），女，硕士，主治医师，研究方向：肿瘤综合治疗，E-mail:327790460@qq.com。
通讯作者：沈娜（1987-），女，硕士，主治医师，研究方向：肿瘤综合治疗，E-mail:9205858266@qq.com。
更新日期/Last Update: 2025-03-15