JAMA Oncology:NRAS和BRAF突变与高危型原发黑色素瘤生存期的关系

2015-04-14 Zhang JL译 MedSci原创

NRAS与BRAF突变在多年以前已经发现存在于黑色素瘤中。然而,这两个基因突变对患者生存率的影响却尚未阐明。为了研究高危型黑色素瘤的死亡与这两个基因突变的关系,为黑色素瘤患者随访以及后续辅助治疗的需要评估,研究人员对此进行了研究。该项研究结果发表在最新一期JAMA Oncology杂志上。该项研究目的,在于阐明NRAS和BRAF突变与原发黑色素瘤的生存率以及肿瘤特征之间的关系。研究人员进行了一项以

NRAS与BRAF突变在多年以前已经发现存在于黑色素瘤中。然而,这两个基因突变对患者生存率的影响却尚未阐明。为了研究高危型黑色素瘤的死亡与这两个基因突变的关系,为黑色素瘤患者随访以及后续辅助治疗的需要评估,研究人员对此进行了研究。该项研究结果发表在最新一期JAMA Oncology杂志上。

该项研究目的,在于阐明NRAS和BRAF突变与原发黑色素瘤的生存率以及肿瘤特征之间的关系。

研究人员进行了一项以人群为基础的研究,平均随访时间为7.6年,包括912个来自美国和澳大利亚的基因、环境和黑色素瘤(GEM)研究中的病例。这些病例均在2000年诊断为黑色素瘤并对其进行了NRAS和BRAF突变分析。

在澳大利亚和美国,原发黑色素瘤中NRAS阳性占13%,BRAF占30%,两者均阴性(WT)占57%。在包括临床病理特点的多变量分析中,相比WT黑色素瘤,NRAS阳性黑素瘤与有丝分裂的存在相关(优势比为1.8,95%置信区间[1.0-3.3]),与较低的白细胞浸润(TIL)等级相关(非急性0.5(0.3-0.8),急性0.3[0.5-0.7][与无TILs相比]),与非头颈部发病部位相关(0.1[0.01-0.6]头皮/颈部VS躯干/骨盆)。而BRAF阳性黑素瘤与更为年轻的患病年龄相关(年龄在50-69为0.7(0.5-1.0),年龄> 70为0.5[0.3 - -0.8][对比年龄< 50岁),与表面扩散亚型相关(结节状为0.5(0.2-1.0);斑点状为0.4(0.2-0.7),和未分类/其他为0.2[0.1-0.5][与表面扩散相比]),和有丝分裂的存在相关(1.7[1.1—-2.6])(所有对比差异P<0.05)。


NRAS和BRAF突变的黑色素瘤的存活率与WT黑色素瘤相比并没有显著差异,NRAS(优势比为1.7,95%置信区间[0.8-3.4]),BRAF(优势比为1.5,95%置信区间[0.8-2.9]),即使年龄、性别、地点、美国癌症联合委员会(AJCC)所评估的肿瘤分级、TIL分级或研究中心有差异。然而,对比低风险(T2a 或更低级)的肿瘤(NRAS突变0.9[0.3-3.0]或BRAF突变0.6[0.2-1.7]),高风险(T2b或更高级)黑色素瘤的生存率显著较差(NRAS2.9[1.1-7.7]或BRAF3.1[1.2-8.5])(P=0.04)。



该研究结论指出,较低TIL等级NRAS阳性的黑色素瘤具有更多的免疫抑制的微环境,使其在免疫疗法中受到一定的影响。对比WT型黑色素瘤,高危型含NRAS或BRAF突变阳性的黑色素瘤的死亡风险增加了差不多3倍,提示这些突变的预后意义值得进一步研究,尤其是高AJCC等级的原发黑色素瘤。

原始出处:

Thomas NE, Edmiston SN, Alexander A, et al. Association Between NRAS and BRAF Mutational Status and Melanoma-Specific Survival Among Patients With Higher-Risk Primary Melanoma.JAMA Oncol. Published online April 09, 2015. doi:10.1001/jamaoncol.2015.0493.

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    2015-09-28 sunylz
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    2016-03-01 tcm99hq
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topicList=[TopicDto(id=13350, encryptionId=16ce133504e, topicName=Oncol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b63894, createdName=minlingfeng, createdTime=Sun May 03 01:03:00 CST 2015, time=2015-05-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1354951, encodeId=5b671354951c2, content=<a href='/topic/show?id=6de63659ed' target=_blank style='color:#2F92EE;'>#BRAF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3659, encryptionId=6de63659ed, topicName=BRAF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Thu Apr 16 13:03:00 CST 2015, time=2015-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1378069, encodeId=d49913e8069f6, content=<a href='/topic/show?id=c29b69004f9' target=_blank style='color:#2F92EE;'>#生存期#</a>, beContent=null, 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encodeId=e4e715586934d, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Thu Apr 16 13:03:00 CST 2015, time=2015-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1564702, encodeId=36ed1564e02a6, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Thu Apr 16 13:03:00 CST 2015, time=2015-04-16, status=1, ipAttribution=)]
    2015-05-03 minlingfeng
  5. 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objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69004, encryptionId=c29b69004f9, topicName=生存期)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e68e415, createdName=juliusluan78, createdTime=Thu Apr 16 13:03:00 CST 2015, time=2015-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1480701, encodeId=8c311480e0108, content=<a href='/topic/show?id=e76836e150' target=_blank style='color:#2F92EE;'>#BRAF突变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3671, encryptionId=e76836e150, topicName=BRAF突变)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eff97667327, createdName=ms4964546379600229, createdTime=Thu Apr 16 13:03:00 CST 2015, time=2015-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558693, encodeId=e4e715586934d, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Thu Apr 16 13:03:00 CST 2015, time=2015-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1564702, encodeId=36ed1564e02a6, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Thu Apr 16 13:03:00 CST 2015, time=2015-04-16, status=1, ipAttribution=)]
    2015-04-16 zhaojie88
  6. 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createdTime=Thu Apr 16 13:03:00 CST 2015, time=2015-04-16, status=1, ipAttribution=)]
  7. 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createdTime=Thu Apr 16 13:03:00 CST 2015, time=2015-04-16, status=1, ipAttribution=)]
  8. 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