肝癌ttl是什么意思

原发性肝细胞癌(HCC)是世界上最常见的恶性肿瘤之一,每年约有70万新患者被确诊[1].
我国是乙肝大国,同时也是肝细胞癌发生大国,肝细胞癌严重危害我国人民的身体健康,也给社会及人们带来巨大的损失[2].
而当前,作为肝细胞癌最主要治疗方式,手术切除仍是众多肝癌早期及部分中晚期患者的首选[3-4].
但是,肝癌切除术后缺少较为可靠的预后指标,很难在切除术后做出科学、合理的判断,从而进行针对性的辅助治疗[5].
m6A甲基化广泛存在于RNA中,参与细胞多种生命活动,在肿瘤的发生、发展中也被报道发挥着重要的作用[6-8].
m6A甲基化过程中存在3种甲基化酶:METTL3、METTL14及WTAP,2种去甲基化酶:FTO与ALKBH5[9].
m6A水平在不同肿瘤或不同细胞系中显著不同,在肝脏、肾脏及脑组织中较高存在[10].
METTL14是一种十分重要的m6A甲基化酶,在RNA的m6A甲基化过程中扮演到关键的角色,同时也被发现可能在多种肿瘤的发生或发展过程中起到作用[11].
Wang等报道,敲低METTL3和METTL14可导致m6AMETTL14asapredictorofpostoperativesurvivaloutcomesofpatientswithhepatocellularcarcinomaZHOUTengfei,RENZifu,CHENChaoshuangDepartmentofInternalMedicine,92493HospitalofPLA,Huludao125000,China摘要:目的探究RNA甲基转移酶METTL14在肝细胞癌(HCC)中的表达,及其临床意义.
方法采用免疫组织化学染色的方法,检测METTL14在147对肝癌、癌旁肝组织中的表达,根据病理医师的评分,把147例肝癌组织表达分为METTL14高表达组与METTL14低表达组,通过卡方检验分析其表达量高低与临床病理指标的相关性;应用Kaplan-Meier方法分析METTL14表达水平与肝癌患者术后预后生存的关系,包括总生存期与无瘤生存期;运用COX回归模型对METTL14表达与肝癌患者术后的总生存期与无瘤生存期进行单因素分析以及多因素分析,以探索METTL14的表达水平是否可作为肝癌患者术后预后的独立预后危险因素.
结果与癌旁组织相比,METTL14在HCC组织中表达明显降低(P50GenderMaleFemaleHBsAg+-AFP(μg/L)≤400>400ALB(μg/L)≤34>34ALT(μg/L)≤40>40PathologicalsatelliteYesNoMVIYesNoEncapsulationYesNoPortalveintumorthrombusYesNoTumorsize(cm)≤5>5TumornumberSingleMultipleBCLCABorCTNMI-IIIII-IVMETTL14low(67)43(64.
18%)24(35.
82%)58(86.
57%)9(13.
43%)60(89.
55%)7(10.
45%)26(38.
81%)41(61.
19%)4(05.
97%)63(94.
03%)26(38.
81%)41(61.
19%)42(62.
69%)25(37.
31%)53(79.
10%)14(20.
90%)22(33.
33%)44(66.
67%)28(41.
79%)39(58.
21%)12(17.
91%)55(82.
09%)55(82.
09%)12(17.
91%)29(43.
28%)38(56.
72%)30(44.
78%)37(55.
22%)METTL14high(80)43(53.
75%)37(46.
25%)68(85.
00%)12(15.
00%)71(88.
75%)9(11.
25%)32(40.
00%)48(60.
00%)3(03.
90%)74(96.
10%)33(41.
25%)47(58.
75%)38(47.
50%)42(52.
50%)55(68.
75%)25(31.
25%)26(32.
50%)54(67.
50%)22(27.
50%)58(72.
50%)26(32.
50%)54(67.
50%)69(86.
25%)11(13.
75%)44(55.
00%)36(45.
00%)49(61.
25%)31(38.
75%)P0.
2010.
7870.
8760.
8830.
5640.
7630.
0660.
1570.
9150.
0690.
0440.
4890.
1570.
046HBsAg:HepatitisBvirussurfaceantigen;AFP:α-fetoprotein;TNM:Tumor-Nodes-Metastasis;BCLC:BarcelonaClinicLiverCancerStaging.
JSouthMedUniv,2020,40(4):567-572http://www.
j-smu.
com··570在我们的研究中,与癌旁组织相比,METTL14在肝癌中较为显著地表达降低,这符合前人在肝癌中m6A的研究,尤其是肝癌中的m6A水平较癌旁有所降低[13].
而至于METTL14的表达与肝癌预后相关的机制,已有研究者报道METTL14在肝癌中的分子生物学功能,且其具有一定的抑制肝癌转移的能力.
经过后期研究,发现METTL14可能通过增加m6A的水平,进而增强部分具有抑癌作用相关基因的表达与稳定性,具体涉及机制可能是通过IGF2BPs这个家族来识别m6A信息,进而传递增强相应mRNA稳定性的信息[30].
综上所述,患者HCC组织中METTL14的低表达,预示着其HCC切除术后不良的总生存期与无瘤生存期,作为HCC的总生存期及无瘤生存期的一个独立预后因素,可能为临床治疗提供了新的指导与依据,并且可能作为一个新的术后预后指标.
METTL14可能在HCC的发生、发展中也发挥着重要作用,其在HCC中的CharacteristicsAge(year)GenderHBVAFP(μg/L)ALB(μg/L)ALT(μg/L)PathologicalsatelliteMVIEncapsulationPortalveintumorthrombusTumorsize(cm)TumornumberBCLCTNMMETTL14≤50vs>50MalevsfemalePositivevsNegetive≤400vs>400≤34vs>34≤40vs>40YesvsNoYesvsNoYesvsNoYesvsNo≤5vs>5SinglevsMultipleB/Cvs0/AIII-IVvsI-IIHighvsLowOS(Univariateanalysis)HR0.
9760.
6771.
3171.
4101.
7221.
0751.
7922.
0370.
7032.
6621.
5801.
2662.
4292.
3710.
67295%CI0.
6730.
3800.
7240.
9660.
8000.
7391.
2271.
2960.
4681.
8071.
0110.
7731.
6611.
6270.
5291.
4161.
2062.
3972.
0603.
7081.
5662.
6153.
2021.
0563.
9232.
4702.
0733.
5523.
4550.
853P0.
8980.
1850.
3670.
0750.
1650.
7040.
0030.
0020.
0890.
0000.
0450.
3500.
0000.
0000.
001OS(Multivariateanalysis)HR------1.
608--2.
222----0.
69795%CI------1.
084--1.
486----0.
549------2.
388--3.
32----0.
884P------0.
018--0.
000----0.
003表2队列1中肝癌病人总生存期的单因素与多因素分析Tab.
2UnivariateandmultivariateanalysisofoverallsurvivalofpatientsinCohort1CharacteristicsAge(year)GenderHBVAFP(μg/L)ALB(μg/L)ALT(μg/L)PathologicalsatelliteMVIEncapsulationPortalveintumorthrombusTumorsize(cm)TumornumberBCLCTNMMETTL14≤50vs>50MalevsfemalePositivevsNegetive≤400vs>400≤34vs>34≤40vs>40YesvsNoYesvsNoYesvsNoYesvsNo≤5vs>5SinglevsMultipleB/Cvs0/AIII-IVvsI-IIHighvsLowDFS(Univariateanalysis)HR0.
8680.
7271.
3641.
4681.
8160.
9091.
7672.
0460.
8042.
3482.
2971.
0982.
1482.
2990.
72795%CI0.
6100.
4360.
7941.
0280.
7950.
6401.
2371.
3520.
5511.
5981.
4920.
6811.
4961.
5950.
5811.
2341.
2132.
3422.
0974.
1481.
2912.
5233.
0951.
1723.
4503.
5371.
7713.
0843.
3140.
911P0.
4300.
2220.
2610.
0350.
1570.
5930.
0020.
0010.
2560.
0000.
0000.
7000.
0000.
0000.
006DFS(Multivariateanalysis)HR------1.
530--1.
7631.
796-0.
71495%CI------1.
050--1.
1281.
217-0.
572------2.
231--2.
7552.
651-0.
892P------0.
027--0.
0130.
003-0.
003表3队列1中肝癌病人无瘤生存期的单因素与多因素分析Tab.
3Univariateandmultivariateanalysisofdisease-freesurvivalofpatientsinCohort1http://www.
j-smu.
comJSouthMedUniv,2020,40(4):567-572··571调控机制仍需更加深入地研究.
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(编辑:余诗诗)JSouthMedUniv,2020,40(4):567-572http://www.
j-smu.
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