Gastroenterology:肠癌防控中国突破:血液多基因甲基化检测可实现结直肠癌早筛和复发预测

2021-11-05 “ 生物世界”公众号 “ 生物世界”公众号

这是中国团队首次在全球范围内实现结直肠癌筛查及复发预测技术手段合二为一。常艾克亦是全球第一款具备结直肠癌早期筛查和术后监测复合功能的产品。

近日,国际胃肠疾病领域顶级学术期刊 Gastroenterology(IF=22.7)发表了由上海鹍远生物技术有限公司(以下简称“鹍远生物”)联合复旦大学附属中山医院、复旦大学附属肿瘤医院、广州市第一人民医院、南方医科大学南方医院、四川大学华西医院、大连大学附属新华医院的重磅科研成果:A multi-locus blood-basedassay targeting circulating tumor DNA methylation enables early detection andearly relapse prediction of colorectal cancer(血液多基因甲基化检测可实现结直肠癌早筛和复发预测)。

该研究系国内团队第一次系统展示多基因甲基化检测方法(ColonAiQ,常艾克)从标志物筛选、优化到验证的完整过程。常艾克检测结直肠癌平均AUC:0.93,结直肠癌和进展期腺瘤平均AUC:0.84,结直肠癌(I-IV期)的综合灵敏度为86%(149/173),对照组健康人群的检测特异性为92%(125/136)。

这是中国团队首次在全球范围内实现结直肠癌筛查及复发预测技术手段合二为一。常艾克亦是全球第一款具备结直肠癌早期筛查和术后监测复合功能的产品。

据世界卫生组织国际癌症研究署(IARC)发布的2020年全球最新癌症负担数据显示,世界范围内,结直肠癌已成为第三大常见癌症;2020年全世界有超过193万人被新确诊为结直肠癌,发病率位居所有癌种第三位;超过93万人死于结直肠癌,死亡率位居所有癌种第二位。2020年,中国有超过55万人新患结直肠癌,结直肠癌发病率跃居国内所有癌种第二位,超过28万人死于结直肠癌;多数结直肠癌患者在确诊时已属于中晚期。因而,早筛、早诊对于结直肠癌整体防控尤为重要。

就结直肠癌早筛而言,尽管肠镜检查被认为是结直肠癌诊断的金标准,但受制于肠镜的依从性和可及性,更多的患者倾向于基于血液的无创检查方式;另外,准确地预测肿瘤复发,将有助于优化辅助治疗方案;合理安排术后监测随访,及早发现肿瘤复发转移,及时的干预治疗仍有可能使复发转移癌患者重新获得治愈机会,延长生存期。因此,精准的复发预测和动态监测仍是结直肠癌诊治中亟需解决的需求。

研究团队基于基因甲基化异常与癌症发生的相关性,探讨了血液样本ctDNA甲基化对结直肠癌及腺瘤的筛查诊断以及预测肿瘤术后复发的性能,结果显示,多基因甲基化有望成为解决临床上结直肠癌的早筛和复发监测问题的新型“肿瘤标志物”。

首先,研究人员对于常艾克标志物进行了严谨的筛选。研究人员在过往PanSeer研究中筛选出 595 个癌症相关基因组区域的基础上(图1),进一步通过对组织样本的甲基化分析,筛选出前150个差异甲基化区域(DMRs)(图2A)。考虑到简化多重qPCR 检测方法在临床上的适用性,研究人员进一步缩小甲基化标志物的范围;最终选择出6种在组织和血浆中具有更高检测能力的标志物,用于多位点血液检测,并命名为常艾克(图2C和2D)。

图1.研究设计

接下来的常艾克标志物验证阶段,研究团队在507 个血浆样本中对锁定的常艾克模型进行盲法验证,发现该模型能够检测到173例结直肠癌患者中的 86%,在结肠镜阴性对照(136例)中的特异性为 92%;并且常艾克的敏感性随着结直肠癌的疾病分期进展和肿瘤大小的增加而升高(图2E和2F)。

表1. ColonAiQ 在验证结肠癌早期检测中的表现

图2.模型中甲基化标志物的筛选

随后,研究团队对常艾克与其他非侵入性筛查方法进行了比较;相比其他非侵入性筛查方法如粪便隐血试验(FIT)、癌胚抗原(CEA)以及Septin9单位点基因甲基化,常艾克具有显着优越性。在142 名接受常艾克的受试者同样接受了粪便隐血试验(FIT),常艾克在所有肠癌疾病阶段的表现均优于 FIT(88.3% vs 59.7%),尤其是在 I 期(85.7% vs 28.6%,图 3D)。与 CEA 相比,常艾克同样显着优于CEA,两者对早期 (I/II) 肠癌病例的检出率分别为80-92% 和 17-47%(图3E)。与 Septin9 相比,6种标志物的组合可以比单独的标志物捕获更全面的肿瘤表观遗传异质性(图 2G)。

对于常艾克在结直肠癌预后监测中应用潜力,研究团队也进行了探索。所有结直肠癌患者中,39 名患者在手术切除肿瘤前 1-2 天和术后 17-34 天提供了血样。术前常艾克检测阳性的 33 例患者中,7例(2例II期,5例III期)在术后42至238天出现肿瘤复发(中位数117天)。研究者观察到复发组和非复发组术后样本的常艾克评分存在显着差异 (p=0.00017)(图 3F)。相应的数据表明常艾克在预测结直肠癌的早期复发方面具有明确的识别能力,后续多中心扩大验证正在进行中。

图3. 模型的建立和验证

该研究的通讯作者复旦大学附属中山医院周平红教授表示:结直肠癌的早筛、早诊是结直肠癌防控的重点工作;虽然肠镜是肠癌诊断的“金标准”,但受限于我国肠镜的整体普及率及依从性,目前我国肠癌筛查策略仍然比较“基础”。在这个多中心研究中,我们纳入了相对较多的早癌以及癌前病变样本,因为早癌和癌前病变才是筛查的重点、难点。从目前结果看,常艾克结直肠癌的筛查性能优异,令人满意;而且血液样本相对方便,更有利于提高肠癌临床筛查的依从性。

该研究的第一作者及共同通讯作者复旦大学附属肿瘤医院蔡国响教授表示:目前结直肠癌无创筛查,多采用粪便隐血检测或流行病学量表调查,上海地区也是全国较早开展大规模结直肠癌无创筛查的城市。从本研究结果看,血液样本多基因甲基化检测有望作为结直肠癌筛查策略中的重要补充部分。另外我们通过这个研究还看到了血液样本ctDNA甲基化在肠癌术后复发预测中的潜力,这在其他研究中鲜有报道。目前的结果令人振奋,这会给临床医生在评估结直肠癌术后复发多一个重要的工具手段;同时也再次提示“DNA甲基化生物标志物”在结直肠癌早筛、早诊、复发监测等全流程管理中的应用价值。

该研究共同通讯作者鹍远生物联合创始人兼首席技术官刘蕊博士表示:该研究首先系统地展示了甲基化基因分子靶标从筛选、评价验证到临床转化的逻辑过程。我们建立了一套系统完整的癌症标志物的筛选,可以延展到不同癌种不同临床问题的相关标志物开发。在我们最终筛选出的六个位点中,有些交叉在已知的,有明确肠癌相关性的标志物。这也从侧面证明了我们的筛选体系的正确性,高效性,同时可以发现创新性靶点的能力。其次,这个研究的重点是临床转化,相比NGS等复杂繁琐的分子检测技术,最后通过多重定量PCR方法学来实现相应检测,充分考虑了临床适宜性及国内医疗实情,更具有商业转化价值和便于落地基层医疗机构。最后,该研究也充分展示了血液检测的临床应用延展性,不仅可以涵盖癌症的早期检测,而且可以有效地评估MRD,对早期复发有预判作用,并且可以有效地预后监控,从而覆盖癌症病人的全流程管理。

鹍远生物联合创始人、首席执行官张江立先生表示:在鹍远的整个产品体系中,结直肠癌是非常重要的一个板块,鹍远从成立之初就开始了结直肠癌筛查和术后监测技术的研发。经过不断的探索,我们聚焦在血液样本多基因甲基化检测技术上。首先,血液样本依从性很好,更符合我国目前肿瘤筛查的主要场景,如体检中心、医院、政府民生工程等。其次,血液样本的扩展性和普适性更好。我们的技术平台可以支持我们从不同癌种中去筛查更多潜在有价值的甲基化标志物;从而开发出更多的癌症筛查产品。

原始出处:

Guo X. Cai, et al. A Multilocus Blood-Based Assay Targeting Circulating Tumor DNA Methylation Enables Early Detection and Early Relapse Prediction of Colorectal Cancer. Gastroenterology, 2021.

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GetPortalCommentsPageByObjectIdResponse(id=1505341, encodeId=0d9b150534109, content=<a href='/topic/show?id=7730e85412' target=_blank style='color:#2F92EE;'>#Gastroenterology#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7854, encryptionId=7730e85412, topicName=Gastroenterology)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5fc29706655, createdName=chaojitidian, createdTime=Sun Nov 07 10:16:47 CST 2021, time=2021-11-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1067599, encodeId=6655106e59982, content=赞, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=801b5560292, createdName=杨致, createdTime=Sat Nov 06 15:44:37 CST 2021, time=2021-11-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1067467, encodeId=749f106e4677b, content=谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=644b2182796, createdName=1207866fm50(暂无昵称), createdTime=Sat Nov 06 08:13:13 CST 2021, time=2021-11-06, status=1, ipAttribution=)]
  3. [GetPortalCommentsPageByObjectIdResponse(id=1754469, encodeId=5a511e54469fa, content=<a href='/topic/show?id=44e2431e1c6' target=_blank style='color:#2F92EE;'>#多基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43171, encryptionId=44e2431e1c6, topicName=多基因)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b34b36693912, createdName=syscxl, createdTime=Sun May 22 02:16:47 CST 2022, time=2022-05-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1712961, encodeId=2ea71e129614b, content=<a href='/topic/show?id=9a1c289680' target=_blank style='color:#2F92EE;'>#AST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2896, encryptionId=9a1c289680, topicName=AST)], attachment=null, authenticateStatus=null, createdAvatar=null, 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topicList=[TopicDto(id=41795, encryptionId=691941e95d3, topicName=基因甲基化)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e2c339, createdName=by2009, createdTime=Tue Aug 02 07:16:47 CST 2022, time=2022-08-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2065462, encodeId=9b1e2065462bd, content=<a href='/topic/show?id=94ffe853a7' target=_blank style='color:#2F92EE;'>#Gastroenterol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7853, encryptionId=94ffe853a7, topicName=Gastroenterol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0bed488, createdName=jktdtl, createdTime=Thu Aug 18 11:16:47 CST 2022, time=2022-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1453596, encodeId=a3b41453596f3, content=<a href='/topic/show?id=098ee8679ad' target=_blank style='color:#2F92EE;'>#结直肠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78679, encryptionId=098ee8679ad, topicName=结直肠)], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=9ace5575596, createdName=crystal0564, createdTime=Sun Nov 07 10:16:47 CST 2021, time=2021-11-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1456926, encodeId=ddb814569263c, content=<a href='/topic/show?id=7de159498d1' target=_blank style='color:#2F92EE;'>#早筛#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=59498, encryptionId=7de159498d1, topicName=早筛)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a10e5815774, createdName=nakerunner, createdTime=Sun Nov 07 10:16:47 CST 2021, time=2021-11-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1505341, encodeId=0d9b150534109, content=<a href='/topic/show?id=7730e85412' target=_blank style='color:#2F92EE;'>#Gastroenterology#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7854, encryptionId=7730e85412, topicName=Gastroenterology)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5fc29706655, createdName=chaojitidian, createdTime=Sun Nov 07 10:16:47 CST 2021, time=2021-11-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1067599, encodeId=6655106e59982, content=赞, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=801b5560292, createdName=杨致, createdTime=Sat Nov 06 15:44:37 CST 2021, time=2021-11-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1067467, encodeId=749f106e4677b, content=谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=644b2182796, createdName=1207866fm50(暂无昵称), createdTime=Sat Nov 06 08:13:13 CST 2021, time=2021-11-06, status=1, ipAttribution=)]
    2022-09-08 许安
  4. [GetPortalCommentsPageByObjectIdResponse(id=1754469, encodeId=5a511e54469fa, content=<a href='/topic/show?id=44e2431e1c6' target=_blank style='color:#2F92EE;'>#多基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43171, encryptionId=44e2431e1c6, topicName=多基因)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b34b36693912, createdName=syscxl, createdTime=Sun May 22 02:16:47 CST 2022, time=2022-05-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1712961, encodeId=2ea71e129614b, content=<a href='/topic/show?id=9a1c289680' target=_blank style='color:#2F92EE;'>#AST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2896, encryptionId=9a1c289680, topicName=AST)], attachment=null, authenticateStatus=null, createdAvatar=null, 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GetPortalCommentsPageByObjectIdResponse(id=1067467, encodeId=749f106e4677b, content=谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=644b2182796, createdName=1207866fm50(暂无昵称), createdTime=Sat Nov 06 08:13:13 CST 2021, time=2021-11-06, status=1, ipAttribution=)]
  5. 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GetPortalCommentsPageByObjectIdResponse(id=1067467, encodeId=749f106e4677b, content=谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=644b2182796, createdName=1207866fm50(暂无昵称), createdTime=Sat Nov 06 08:13:13 CST 2021, time=2021-11-06, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1754469, encodeId=5a511e54469fa, content=<a href='/topic/show?id=44e2431e1c6' target=_blank style='color:#2F92EE;'>#多基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43171, encryptionId=44e2431e1c6, topicName=多基因)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b34b36693912, createdName=syscxl, createdTime=Sun May 22 02:16:47 CST 2022, time=2022-05-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1712961, encodeId=2ea71e129614b, content=<a href='/topic/show?id=9a1c289680' target=_blank style='color:#2F92EE;'>#AST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2896, encryptionId=9a1c289680, topicName=AST)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8b9831894722, createdName=ms24272190615788285182, createdTime=Sun Oct 16 12:16:47 CST 2022, time=2022-10-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2073465, encodeId=603820e346527, content=<a href='/topic/show?id=9d4ee84647' target=_blank style='color:#2F92EE;'>#GAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7846, encryptionId=9d4ee84647, topicName=GAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e2dd327, createdName=许安, createdTime=Thu Sep 08 00:16:47 CST 2022, time=2022-09-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2060546, encodeId=de3b206054617, content=<a href='/topic/show?id=691941e95d3' target=_blank style='color:#2F92EE;'>#基因甲基化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41795, encryptionId=691941e95d3, topicName=基因甲基化)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e2c339, createdName=by2009, createdTime=Tue Aug 02 07:16:47 CST 2022, time=2022-08-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2065462, encodeId=9b1e2065462bd, content=<a href='/topic/show?id=94ffe853a7' target=_blank style='color:#2F92EE;'>#Gastroenterol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7853, encryptionId=94ffe853a7, topicName=Gastroenterol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0bed488, createdName=jktdtl, createdTime=Thu Aug 18 11:16:47 CST 2022, time=2022-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1453596, encodeId=a3b41453596f3, content=<a href='/topic/show?id=098ee8679ad' target=_blank style='color:#2F92EE;'>#结直肠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78679, encryptionId=098ee8679ad, topicName=结直肠)], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=9ace5575596, createdName=crystal0564, createdTime=Sun Nov 07 10:16:47 CST 2021, time=2021-11-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1456926, encodeId=ddb814569263c, content=<a href='/topic/show?id=7de159498d1' target=_blank style='color:#2F92EE;'>#早筛#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=59498, encryptionId=7de159498d1, topicName=早筛)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a10e5815774, createdName=nakerunner, createdTime=Sun Nov 07 10:16:47 CST 2021, time=2021-11-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1505341, encodeId=0d9b150534109, content=<a href='/topic/show?id=7730e85412' target=_blank style='color:#2F92EE;'>#Gastroenterology#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7854, encryptionId=7730e85412, topicName=Gastroenterology)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5fc29706655, createdName=chaojitidian, createdTime=Sun Nov 07 10:16:47 CST 2021, time=2021-11-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1067599, encodeId=6655106e59982, content=赞, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=801b5560292, createdName=杨致, createdTime=Sat Nov 06 15:44:37 CST 2021, time=2021-11-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1067467, encodeId=749f106e4677b, content=谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=644b2182796, createdName=1207866fm50(暂无昵称), createdTime=Sat Nov 06 08:13:13 CST 2021, time=2021-11-06, status=1, ipAttribution=)]
  7. [GetPortalCommentsPageByObjectIdResponse(id=1754469, encodeId=5a511e54469fa, content=<a href='/topic/show?id=44e2431e1c6' target=_blank style='color:#2F92EE;'>#多基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43171, encryptionId=44e2431e1c6, topicName=多基因)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b34b36693912, createdName=syscxl, createdTime=Sun May 22 02:16:47 CST 2022, time=2022-05-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1712961, encodeId=2ea71e129614b, content=<a href='/topic/show?id=9a1c289680' target=_blank style='color:#2F92EE;'>#AST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2896, encryptionId=9a1c289680, topicName=AST)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8b9831894722, createdName=ms24272190615788285182, createdTime=Sun Oct 16 12:16:47 CST 2022, time=2022-10-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2073465, encodeId=603820e346527, content=<a href='/topic/show?id=9d4ee84647' target=_blank style='color:#2F92EE;'>#GAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7846, encryptionId=9d4ee84647, topicName=GAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e2dd327, createdName=许安, createdTime=Thu Sep 08 00:16:47 CST 2022, time=2022-09-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2060546, encodeId=de3b206054617, content=<a href='/topic/show?id=691941e95d3' target=_blank style='color:#2F92EE;'>#基因甲基化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41795, encryptionId=691941e95d3, topicName=基因甲基化)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e2c339, createdName=by2009, createdTime=Tue Aug 02 07:16:47 CST 2022, time=2022-08-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2065462, encodeId=9b1e2065462bd, content=<a href='/topic/show?id=94ffe853a7' target=_blank style='color:#2F92EE;'>#Gastroenterol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7853, encryptionId=94ffe853a7, topicName=Gastroenterol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0bed488, createdName=jktdtl, createdTime=Thu Aug 18 11:16:47 CST 2022, time=2022-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1453596, encodeId=a3b41453596f3, content=<a href='/topic/show?id=098ee8679ad' target=_blank style='color:#2F92EE;'>#结直肠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78679, encryptionId=098ee8679ad, topicName=结直肠)], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=9ace5575596, createdName=crystal0564, createdTime=Sun Nov 07 10:16:47 CST 2021, time=2021-11-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1456926, encodeId=ddb814569263c, content=<a href='/topic/show?id=7de159498d1' target=_blank style='color:#2F92EE;'>#早筛#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=59498, encryptionId=7de159498d1, topicName=早筛)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a10e5815774, createdName=nakerunner, createdTime=Sun Nov 07 10:16:47 CST 2021, time=2021-11-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1505341, encodeId=0d9b150534109, content=<a href='/topic/show?id=7730e85412' target=_blank style='color:#2F92EE;'>#Gastroenterology#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7854, encryptionId=7730e85412, topicName=Gastroenterology)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5fc29706655, createdName=chaojitidian, createdTime=Sun Nov 07 10:16:47 CST 2021, time=2021-11-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1067599, encodeId=6655106e59982, content=赞, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=801b5560292, createdName=杨致, createdTime=Sat Nov 06 15:44:37 CST 2021, time=2021-11-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1067467, encodeId=749f106e4677b, content=谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=644b2182796, createdName=1207866fm50(暂无昵称), createdTime=Sat Nov 06 08:13:13 CST 2021, time=2021-11-06, status=1, ipAttribution=)]
    2021-11-07 nakerunner
  8. [GetPortalCommentsPageByObjectIdResponse(id=1754469, encodeId=5a511e54469fa, content=<a href='/topic/show?id=44e2431e1c6' target=_blank style='color:#2F92EE;'>#多基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43171, encryptionId=44e2431e1c6, topicName=多基因)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b34b36693912, createdName=syscxl, createdTime=Sun May 22 02:16:47 CST 2022, time=2022-05-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1712961, encodeId=2ea71e129614b, content=<a href='/topic/show?id=9a1c289680' target=_blank style='color:#2F92EE;'>#AST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2896, encryptionId=9a1c289680, topicName=AST)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8b9831894722, createdName=ms24272190615788285182, createdTime=Sun Oct 16 12:16:47 CST 2022, time=2022-10-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2073465, encodeId=603820e346527, content=<a href='/topic/show?id=9d4ee84647' target=_blank style='color:#2F92EE;'>#GAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7846, encryptionId=9d4ee84647, topicName=GAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e2dd327, createdName=许安, createdTime=Thu Sep 08 00:16:47 CST 2022, time=2022-09-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2060546, encodeId=de3b206054617, content=<a href='/topic/show?id=691941e95d3' target=_blank style='color:#2F92EE;'>#基因甲基化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, 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beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78679, encryptionId=098ee8679ad, topicName=结直肠)], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=9ace5575596, createdName=crystal0564, createdTime=Sun Nov 07 10:16:47 CST 2021, time=2021-11-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1456926, encodeId=ddb814569263c, content=<a href='/topic/show?id=7de159498d1' target=_blank style='color:#2F92EE;'>#早筛#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=59498, encryptionId=7de159498d1, topicName=早筛)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a10e5815774, createdName=nakerunner, createdTime=Sun Nov 07 10:16:47 CST 2021, time=2021-11-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1505341, encodeId=0d9b150534109, content=<a href='/topic/show?id=7730e85412' target=_blank style='color:#2F92EE;'>#Gastroenterology#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7854, encryptionId=7730e85412, topicName=Gastroenterology)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5fc29706655, createdName=chaojitidian, createdTime=Sun Nov 07 10:16:47 CST 2021, time=2021-11-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1067599, encodeId=6655106e59982, content=赞, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=801b5560292, createdName=杨致, createdTime=Sat Nov 06 15:44:37 CST 2021, time=2021-11-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1067467, encodeId=749f106e4677b, content=谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=644b2182796, createdName=1207866fm50(暂无昵称), createdTime=Sat Nov 06 08:13:13 CST 2021, time=2021-11-06, status=1, ipAttribution=)]
  9. [GetPortalCommentsPageByObjectIdResponse(id=1754469, encodeId=5a511e54469fa, content=<a href='/topic/show?id=44e2431e1c6' target=_blank style='color:#2F92EE;'>#多基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43171, encryptionId=44e2431e1c6, topicName=多基因)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b34b36693912, createdName=syscxl, createdTime=Sun May 22 02:16:47 CST 2022, time=2022-05-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1712961, encodeId=2ea71e129614b, content=<a href='/topic/show?id=9a1c289680' target=_blank style='color:#2F92EE;'>#AST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2896, encryptionId=9a1c289680, topicName=AST)], attachment=null, authenticateStatus=null, createdAvatar=null, 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beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78679, encryptionId=098ee8679ad, topicName=结直肠)], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=9ace5575596, createdName=crystal0564, createdTime=Sun Nov 07 10:16:47 CST 2021, time=2021-11-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1456926, encodeId=ddb814569263c, content=<a href='/topic/show?id=7de159498d1' target=_blank style='color:#2F92EE;'>#早筛#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=59498, encryptionId=7de159498d1, topicName=早筛)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a10e5815774, createdName=nakerunner, createdTime=Sun Nov 07 10:16:47 CST 2021, time=2021-11-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1505341, encodeId=0d9b150534109, content=<a href='/topic/show?id=7730e85412' target=_blank style='color:#2F92EE;'>#Gastroenterology#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7854, encryptionId=7730e85412, topicName=Gastroenterology)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5fc29706655, createdName=chaojitidian, createdTime=Sun Nov 07 10:16:47 CST 2021, time=2021-11-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1067599, encodeId=6655106e59982, content=赞, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=801b5560292, createdName=杨致, createdTime=Sat Nov 06 15:44:37 CST 2021, time=2021-11-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1067467, encodeId=749f106e4677b, content=谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=644b2182796, createdName=1207866fm50(暂无昵称), createdTime=Sat Nov 06 08:13:13 CST 2021, time=2021-11-06, status=1, ipAttribution=)]
    2021-11-06 杨致

    0

  10. 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    2021-11-06 1207866fm50(暂无昵称)

    谢谢分享

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