Expression and significance of the LONP1 gene in hepatocellular carcinoma
-
摘要: 目的探讨LONP1基因在肝细胞癌(HCC)组织中的表达情况及临床意义。方法选取由上海芯超生物有限公司提供的在2010年1月-2011年9月病理确诊为HCC的患者90例,根据LONP1蛋白在HCC癌组织中阳性表达程度,分为弱阳性组(n=33)、阳性组(n=24)、强阳性组(n=33)。用免疫组化的方法检测LONP1在癌及癌旁组织中的表达情况,并分析与HCC临床病理特征的关系。计数资料组间比较采用χ2检验或Fisher确切概率法。生存分析采用Kaplan-Meier方法及log-rank检验,影响因素分析采用Cox比例风险回归模型。结果 LONP1蛋白在HCC癌组织中的阳性表达率显著高于癌旁组织(100%vs 8. 9%,χ2=152. 308,P <0. 001)。LONP1蛋白的表达与肿瘤有无包膜、有无合并肝硬化、临床分期和病理分级有关(P值均<0. 05)。弱阳性组中位生存期40. 545个月,阳性组28. 545个月,强阳性组19. 428个月,差异有统计学意义(χ2=32. 058,P <0. 0...Abstract: Objective To investigate the expression and clinical significance of the LONP1 gene in hepatocellular carcinoma( HCC).Methods A total of 90 patients with pathologically confirmed HCC from January 2010 to September 2011 were enrolled,and the microarrays for their HCC tissue and adjacent tissue samples were provided by Shanghai Xinchao Biological Co.,Ltd. According to the level of positive expression of LONP1 in HCC tissue,the patients were divided into weak positive group with 33 patients,positive group with 24 patients,and strong positive group with 33 patients. Immunohistochemistry was used to measure the expression of LONP1 in HCC and adjacent tissue samples,and its association with the clinicopathological features of HCC was analyzed. The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. The Kaplan-Meier method and the log-rank test were used for survival analysis,and the Cox proportional-hazards regression model was used to investigate risk factors. Results The positive expression rate of LONP1 protein in HCC tissue was significantly higher than that in the adjacent tissue( 100% vs 8. 9%,χ2= 152. 308,P < 0. 001). The expression of LONP1 protein was associated with presence or absence of tumor capsule,presence or absence of liver cirrhosis,clinical stage,and pathological grade( all P < 0. 05). There was a significant difference in median survival time between the weak positive group,the positive group,and the strong positive group( 40. 545 months vs 28. 545 months vs 19. 428 months,χ2= 32. 058,P < 0. 001). In HCC patients,median survival time was correlated with the expression of LONP1 protein,pathological grade,and clinical stage( all P < 0. 05). The multivariate Cox analysis showed that with the weak positive expression of LONP1 protein as a reference,positive expression of LONP1 protein( hazard ratio [HR]= 0. 109,95% confidence interval [CI]: 0. 034-0. 349,P < 0. 001) and strong positive expression of LONP1 protein( HR =0. 448,95% CI: 0. 219-0. 918,P = 0. 028) were independent influencing factors for the survival of HCC patients. Conclusion The expression level of LONP1 in HCC tissue is significantly higher than that in adjacent tissue,and the patients with high expression of LONP1 have a significantly shorter survival time than those with low expression.
-
Key words:
- carcinoma,hepatocellular /
- LONP1 /
- prognosis
-
[1] CHEN WQ,ZHENG RS,BAADE PD,et al. Cancer statistics in China,2015[J]. CA Cancer J Clin,2016,66(2):115-132. [2] BULTEAUAL,SZWEDA LI,FRIGUET B. Mitochondrial protein oxidation and degradation in response to oxidative stress and aging[J]. Exp Gerontol,2006,41(7):653-657. [3] TATSUTA T. Protein quality control in mitochondria[J]. J Biochem,2009,146(4):455-461. [4] GIBELLINI L,LOSI L,de BIASI S,et al. LONP1 differently modulates mitochondrial function and bioenergetics of primary versus metastatic colon cancer cells[J]. Front Oncol,2018,8:254. [5] NIE XB,LI M,LU B,et al. Down-regulating overexpressed human lon in cervical cancer suppresses cell proliferation and bioenergetics[J]. PLo S One,2013,8(11):e81084. [6] LIU Y,LAN L,HUANG K,et al. Inhibition of Lon blocks cell proliferatiaon,enhances chemosensitivity by promoting apoptosis and decreases cellular bioenergetics of bladder cancer:potential roles of Lon as a prognostic marker and therapeutic target in baldder cancer[J]. Oncotarget,2014,5(22):11209-11224. [7] National Health and Family Planning Commission of the People’s Repubilc of China. Diagnosis,management,and treatment of hepatocellular carcinoma(V2017)[J]. J Clin Hepatol,2017,33(8):1419-1431.(in Chinese)中华人民共和国国家卫生和计划生育委员会.原发性肝癌诊疗规范(2017年版)[J].临床肝胆病杂志,2017,33(8):1419-1431. [8] Chinese Society of Liver Cancer,Chinese Anti-Cancer Association; Liver Cancer Study Group,Chinese Society of Pathology,Chinese Medical Association; Chinese Society of Pathology,Chinese Anti-Cancer Association,et al. Standardized pathological diagnosis guidelines for primary liver cancer(2015)[J]. J Clin Hepatol,2015,31(6):833-839.(in Chinese)中国抗癌协会肝癌专业委员会,中华医学会肝病学分会肝癌学组,中国抗癌协会病理专业委员会,等.原发性肝癌规范化病理诊断指南(2015年版)[J].临床肝胆病杂志,2015,31(6):833-839. [9] WANG YP,TANG DX. Expression of Yes-associated protein in liver cancer and its correlation with clinicopathological features and prognosis of liver cancer patients[J]. Int J Clin Exp Med,2015,8(1):1080-1086. [10] CHENG CW,KUO CY,FAN CC,et al. Overexpression of Lon contributes to survival and aggressive phenotype of cancer cells through mitochondrial complex I-mediated generation of reactive oxygen species[J]. Cell Death Dis,2013,4:e681. [11] GIBELLINI L,PINTI M,BORALDI F,et al. Silencing of mitochondrial Lon protease deeply impairs mitochondrial proteome and function in colon cancer cells[J]. FASEB J,2014,28(12):5122-5135. [12] GILLIES RJ,GATENBY RA. Adaptive landscapes and emergent phenotypes:Why do cancers have high glycolysis?[J].J Bioenerg Biomembr,2007,39(3):251-257. [13] BULTEAU AL,BAYOT A. Mitochondrial proteases and cancer[J]. Biochim Biophys Acta,2011,1807(6):595-601. 期刊类型引用(17)
1. 杨文帅,王立坤,董聪慧,武永萍,石栓柱. 瞬时弹性成像技术联合血清游离脂肪酸对非酒精性脂肪性肝病的诊断价值. 转化医学杂志. 2024(09): 1330-1335 . 百度学术
2. 崔会鹏,田昊宇,关琳,李异玲. 代谢相关性脂肪性肝病无创诊断方法研究进展. 胃肠病学和肝病学杂志. 2022(01): 99-103 . 百度学术
3. 凡军芳,胡静,耿旭,庄兰艮,时照明. 2型糖尿病患者肝脏受控衰减参数与血清25-羟维生素D的相关性. 中华全科医学. 2021(05): 794-797 . 百度学术
4. 陈雅洁,李昭贤,王洋,曹经琳,窦剑. 瞬时弹性成像技术在肝移植围手术期应用的研究进展. 中华器官移植杂志. 2021(08): 501-504 . 百度学术
5. 林俊红,林常青,翁娜,刘宴伟. 中年女性高血压体检者体质指数异常与脂肪肝发病率的相关性研究及护理干预. 全科护理. 2020(10): 1212-1214 . 百度学术
6. 张晓静,林淑珍,张志安,温美兰. FibroTouch技术在诊断非酒精性脂肪性肝病患者肝脂肪变程度中的应用. 临床医学. 2020(04): 79-80 . 百度学术
7. 李萍英,李娟,谢守珍,杨永耿,陆伦根. FibroTouch联合超声和CT检查诊断高原地区非酒精性脂肪性肝病临床应用研究. 实用肝脏病杂志. 2020(06): 817-820 . 百度学术
8. 李正鑫,陈洋溢,赵志敏,吕靖,陈高峰,刘成海. 基于肝脏病理学对慢性乙型肝炎肝硬化患者FibroTouch测量值的影响因素分析. 临床肝胆病杂志. 2019(02): 338-344 . 本站查看
9. 陈中淑. 超声检查在诊断脂肪肝方面的临床应用价值. 当代医药论丛. 2019(10): 26-28 . 百度学术
10. 何义华,罗建君,文安怡,程志生,余志映,吴舒婷. 二至解酲汤治疗酒精性肝病临床研究. 中医学报. 2018(06): 1099-1102 . 百度学术
11. 何妙峰. 腹部B超对健康体检者脂肪肝筛查的价值分析. 深圳中西医结合杂志. 2018(10): 90-91 . 百度学术
12. 王晴晴,胡明芬,杨红洁,禹蔚琴,柏保利,匡小林,庄林. B超在慢性HBV携带者合并非酒精性脂肪性肝病诊断中的应用. 肝脏. 2018(08): 723-727 . 百度学术
13. 王新. 脂肪肝与病毒性肝炎B超鉴别诊断结果的对比研究. 心理月刊. 2018(04): 47-48 . 百度学术
14. 张志伟. 肝功能与血清学指标水平检验对脂肪肝的诊断价值分析. 中外医疗. 2018(34): 11-13 . 百度学术
15. 南胜天. CT及B超在脂肪肝临床诊断中应用的价值. 甘肃科技. 2017(07): 102-103 . 百度学术
16. 庄小芳,孙洁,王晓波,王燕,吴琦琦,王晓忠. 瞬时弹性成像技术诊断非酒精性脂肪性肝病的性能评估. 临床肝胆病杂志. 2017(12): 2366-2371 . 本站查看
17. 杨杰,曹玉芝,徐永升,王雪,刘闯. 373例非酒精性脂肪性肝病FibroTouch检测临床观察. 中国实用医药. 2017(24): 33-34 . 百度学术
其他类型引用(12)
-