细胞周期蛋白依赖性激酶抑制因子3和血清壳多糖酶3样蛋白1、miR⁃106b联合检测在肝癌转移中的预测价值
收稿日期: 2024-12-31
网络出版日期: 2025-05-21
基金资助
重庆市自然科学基金面上项目(cstc2021jcyj-msxmX0985);重庆市渝北区科卫联合医学科研项目(2023YBKW19)
The predictive value of combined detection of cell cycle molecule CDKN3 and serum CHI3L1, miR⁃106b in liver cancer metastasis
Received date: 2024-12-31
Online published: 2025-05-21
目的 探究细胞周期蛋白依赖性激酶抑制因子3(CDKN3)和血清壳多糖酶3样蛋白1(CHI3L1)、微小RNA-106b(miR-106b)联合检测在肝癌转移中的预测价值。 方法 选取2019年9月至2023年12月期间医院收治的肝癌患者100例作为研究对象,纳入肝癌组,将同期87例肝硬化患者作为肝硬化组,96例慢性乙肝患者作为慢性乙肝组、常规体检健康人员98例纳入健康对照组,对比各组血清CHI3L1、细胞周期分子CDKN3、miR-106b水平。将肝癌组按照随访1年期间是否转移分为26例转移组、63例未转移组、11例失随访,对比两组患者基线资料、细胞周期分子CDKN3、miR-106b、血清CHI3L1水平。利用多因素logistic分析肝癌转移的风险因素,利用ROC曲线分析miR-106b、细胞周期分子CDKN3、血清CHI3L1联合检测对肝癌转移的预测价值。 结果 与健康对照组相比,肝癌组、慢性乙型组、肝硬化组的CHI3L1、细胞周期分子CDKN3、血清miR-106b水平升高,且慢性乙型组 < 肝硬化组 < 肝癌组,随肝脏疾病程度不断增加,其呈现升高趋势,差异有统计学意义(P < 0.05)。与未转移组相比,转移组谷丙转氨酶(ALT)、肿瘤> 3 cm占比、CHI3L1、细胞周期素A2(CCNA2)、肿瘤分期 > Ⅲ期占比、细胞周期分子CDKN3、异常凝血酶原、谷氨酰转肽酶(GGT)、miR-106b、总胆汁酸(TBA)、甲胎蛋白(AFP)、肿瘤数量多发占比、谷草转氨酶(AST)水平升高,差异有统计学意义(P < 0.05)。多因素logistic分析结果显示,肝癌转移的风险因素包括ALT、CCNA2、肿瘤 > 3 cm、AST、GGT、肿瘤分期 > Ⅲ期、AFP、CHI3L1、多发肿瘤、miR-106b、细胞周期分子CDKN3、TBA。ROC曲线分析结果显示:miR-106b、血清CHI3L1、细胞周期分子CDKN3联合检测敏感度为93.65%、准确度为84.27%、AUC值为0.776高于单项检测敏感度、准确度、AUC值,差异有统计学意义(P < 0.05)。 结论 细胞周期分子CDKN3和血清CHI3L1、miR-106b水平升高为肝癌转移的风险因素,可用于预测肝癌转移发生情况,且联合检测预测效能显著。
关键词: 细胞周期蛋白依赖性激酶抑制因子3; 壳多糖酶3样蛋白1; 微小RNA-106b; 肝癌转移
杨洪 , 丁钧 , 郭鹏 , 张治清 . 细胞周期蛋白依赖性激酶抑制因子3和血清壳多糖酶3样蛋白1、miR⁃106b联合检测在肝癌转移中的预测价值[J]. 实用医学杂志, 2025 , 41(10) : 1473 -1479 . DOI: 10.3969/j.issn.1006-5725.2025.10.007
Objective To investigate the predictive value of the combination of cell cycle protein-dependent kinase inhibitor 3(CDKN3) and serum chitosanase 3-like protein 1(CHI3L1), and microRNA-106b(miR-106b) assays in hepatocellular carcinoma metastasis. Methods One hundred patients with hepatocellular carcinoma admitted to the hospital between September 2019 and December 2023 were selected as study subjects and included in the hepatocellular carcinoma group, 87 patients with cirrhosis were included as the cirrhosis group during the same period, 96 patients with chronic hepatitis B as the chronic hepatitis B group, and 98 healthy persons undergoing routine physical examination were included in the healthy control group, and the groups were compared with respect to the serum CHI3L1, the cell-cycle molecule CDKN3, and the miR-106b levels. The hepatocellular carcinoma group was divided into 26 metastatic cases, 63 non-metastatic cases, and 11 cases lost to follow-up according to whether they metastasized during the 1-year follow-up period, and baseline data, cell cycle molecules CDKN3, miR-106b, and serum CHI3L1 levels were compared between the two groups. Risk factors for hepatocellular carcinoma metastasis were analyzed using multifactorial logistic, and the predictive value of the combined detection of miR-106b, the cell cycle molecule CDKN3, and serum CHI3L1 for hepatocellular carcinoma metastasis was analyzed using ROC curves. Results Compared with the healthy control group, the levels of CHI3L1, cell cycle molecule CDKN3, and serum miR-106b were elevated in the hepatocellular carcinoma group, chronic type B group, and cirrhosis group, and the chronic type B group < cirrhosis group < hepatocellular carcinoma group, which showed a tendency to be elevated with the increasing degree of liver disease, and the difference was statistically significant(P<0.05). Compared with the non-metastatic group, the metastatic group had higher levels of alanine aminotransferase(ALT), percentage of tumors >3 cm, CHI3L1, cytokinin A2(CCNA2), percentage of tumors with stage > Ⅲ, the cell cycle molecule CDKN3, abnormal plasminogen, glutamyltransferase(GGT), miR-106b, total bile acids(TBA), alpha-fetoprotein(AFP), number of tumors percentage of multiple occurrences, and glutamyltransferase(AST) levels were elevated, and the difference was statistically significant(P<0.05). The results of multifactorial logistics analysis showed that the risk factors for hepatocellular carcinoma metastasis included ALT, CCNA2, tumor > 3 cm, AST, GGT, tumor stage > Ⅲ, AFP, CHI3L1, multiple tumors, abnormally high blood plasminogen, miR-106b, cell cycle molecule CDKN3, TBA. the results of the ROC curve analysis showed that miR -106b, serum CHI3L1, cell cycle molecule CDKN3 combined detection sensitivity was 93.65%, accuracy was 84.27%, and AUC value was 0.776 higher than the sensitivity, accuracy, and AUC value of single detection, and the difference was statistically significant(P < 0.05). Conclusions Elevated levels of cell cycle molecule CDKN3, serum CHI3L1, and miR-106b are risk factors for liver cancer metastasis. It can be used to predict the occurrence of liver cancer metastasis, and the combined detection has significant predictive efficacy.
| 1 | 纪虹,侯婧悦,孟杨,等. 不同营养风险筛查工具对肝癌患者营养状况评定的敏感度、特异度和精准度的分析[J]. 现代消化及介入诊疗, 2023, 28(6) :758-761. |
| 2 | 黄双盈,钱蓉. 手术室人文关怀联合体温管理对肝癌患者术后心理状态、免疫功能及预后的影响[J]. 河北医药, 2023, 45(23): 3660-3663. |
| 3 | 李文磊,栗光明. 肝癌肝移植术后肿瘤复发转移诊治新进展[J]. 器官移植,2025,16(2):208-213. doi:10.12464/j.issn.1674-7445.2025045 |
| 4 | 秦小琰,刘彦尧,康权. 肝癌肝移植术后复发转移的防治策略和靶向免疫治疗[J]. 器官移植,2022,13(2):271-276. doi:10.3969/j.issn.1674-7445.2022.02.018 |
| 5 | 朱志文,阳亮芳,郑杨,等. 周期蛋白依赖激酶抑制因子3通过调控G2/M期检查点促进肝内胆管癌细胞生长并降低对顺铂的敏感性[J]. 实用医学杂志, 2022, 38(22): 2768-2773. doi:10.3969/j.issn.1006-5725.2022.22.002 |
| 6 | 黄梅,崔丽娜,刘黎萍. 益元清肺汤联合依替米星治疗气虚肺热证重症肺炎患者的效果及对血清SAA、ChE、CHI3L1的影响[J]. 世界临床药物, 2024, 45(7): 737-742. |
| 7 | 李传斌,夏磊. miR-203,miR-106b表达与脑梗死后继发癫痫的相关性分析[J]. 中国卫生检验杂志, 2023, 33(19): 2375-2377. |
| 8 | 国家癌症中心,国家肿瘤质控中心肝癌质控专家委员会. 中国肝癌规范诊疗质量控制指标(2022版)[J]. 中华肿瘤杂志, 2022, 44(7): 600-608. doi:10.3760/cma.j.cn112152-20220511-00328 |
| 9 | 朱慧,陆欢平,李天佑,等. CDKN3在口腔鳞状细胞癌中的预后价值及免疫细胞浸润分析[J]. 国际检验医学杂志, 2024, 45(11): 1302-1307. |
| 10 | ZHANG C, SHEN Q, GAO M, et al. The role of Cyclin Dependent Kinase Inhibitor 3( CDKN3 ) in promoting human tumors: Literature review and pan-cancer analysis [J]. Heliyon, 2024, 10(4): 26061. doi:10.1016/j.heliyon.2024.e26061 |
| 11 | 王凡,刘伟,李强,等. CDKN3和FOXA1 mRNA在直肠癌中的表达关系及意义[J]. 河北医学, 2021, 27(1): 84-89. doi:10.3969/J.issn.1006-6233.2021.01.019 |
| 12 | LI Y, ZHOU Y, PEI H, et al. Disruption of BACH1 Protects AC16 Cardiomyocytes Against Hypoxia/ Reoxygenation -Evoked Injury by Diminishing CDKN3 Transcription [J]. Cardiovasc Toxicol, 2024, 24(10): 1105-1115. doi:10.1007/s12012-024-09900-2 |
| 13 | 饶春美,房萌,洪松,等. 壳多糖酶3样蛋白1在原发性肝癌中的检测及其临床价值[J]. 中华检验医学杂志, 2020, 43(7): 725-731. |
| 14 | 王刚,王忠耕,郭嘉鸿. 多层螺旋CT扫描联合血清CHI3 L1、GP73检测在原发性肝癌的临床诊断中的应用价值[J]. 实用癌症杂志, 2022, 37(12): 2046-2049. |
| 15 | 周煜苗,张卫,宗金宝. 血清CHI3L1水平与肝脏疾病之间的关系[J]. 标记免疫分析与临床, 2024, 31(8): 1465-1470. |
| 16 | 童正喜,张克昌,郑奇. 血清高尔基体糖蛋白73、甲胎蛋白、CHI3L1在肝癌中的诊断价值及与患者预后的关系[J]. 热带医学杂志, 2020, 20(6): 779-782. |
| 17 | HE C, HU Z, LIN Z, et al. Chitinase-3 like-protein-1, a prognostic biomarker in patients with hepatocellular carcinoma and concomitant myosteatosis [J]. BMC Cancer, 2024, 24(1): 1-12. doi:10.1186/s12885-024-12808-3 |
| 18 | 蒋锐,邹晓霞,吴莉莉,等. 肝细胞癌患者外周血中miR-30a、miR-106b的表达及其与预后的关系[J]. 现代肿瘤医学, 2022, 30(16): 2969-2974. |
| 19 | MAHBOUDI S, PARIVAR K, MAZAHERI Z, et al. miR - 106b enhances human mesenchymal stem cell differentiation to spermatogonial stem cells under germ cell profile genes involved in TGF-b signaling pathways[J]. In Vitro Cell Dev Biol Anim, 2022, 58(7): 539-548. doi:10.1007/s11626-022-00688-5 |
| 20 | 丛鹏,杨红春,彭勇,等. 肝细胞癌患者外周血miR-30a、miR-106b水平与预后的关系[J]. 中西医结合肝病杂志, 2022, 32(6): 509-512. doi:10.3969/j.issn.1005-0264.2022.06.009 |
| 21 | 张竹,许乐,贾文卓. 基于ROC曲线分析血清miR-375、miR-106b和AFP在肝癌早期诊断中的价值[J]. 标记免疫分析与临床, 2020, 27(5): 779-781. doi:10.11748/bjmy.issn.1006-1703.2020.05.014 |
| 22 | CHEN Z, CHEN X, LEI T, et al. Integrative Analysis of NSCLC Identifies LINC01234 as an Oncogenic lncRNA that Interacts with HNRNPA2B1 and Regulates miR-106b Biogenesis [J]. Mol Ther, 2022, 28(6): 1479-1493. doi:10.1016/j.ymthe.2020.03.010 |
| 23 | 李静博,苏小红. 血清异常凝血酶原联合甲胎蛋白检测在原发性肝癌诊断中的应用[J]. 川北医学院学报,2023,38(8):1066-1068. |
| 24 | 杨结,谢万珍,刘树业. 血清肿瘤标志物联合检测在原发性肝癌诊断中的价值研究[J]. 中国中西医结合外科杂志,2022,28(3):352-358. |
/
| 〈 |
|
〉 |