bet9¾ÅÖÝÌåÓý

¿Í·þÈÈÏß
0711-3703999 £¨ÖÜÒ» - ÖÜÎå 9:00-17:30£©

ctDNAÒºÌå»î¼ìÔÚÁÜ°ÍÁöÖеÄÓ¦ÓÃ

2020-01-13 13:52


ÁÜ°ÍÁöÊÇÒ»×éÆðÔ´ÓÚÍâÖÜÁÜ°Í×éÖ¯µÄ¶ñÐÔѪҺÖ×Áö£¬Æ¾Ö¤ËùÆðÔ´µÄϸ°ûÀàÐͺÍ×éÖ¯²¡ÀíÌØÕ÷·ÖΪ¶àÖÖÑÇÐÍ£¬ÆäÖÎÁÆÒªÁìºÍÔ¤ºóÆÀ¼ÛÒò²î±ðµÄϸ°ûÆðÔ´¡¢²¡ÀíÀàÐͼ°ÇÖÏ®ÐÔ¶ø²î±ð£¬×¼È·µÄÕï¶Ï·ÖÐÍÊÇʵÏÖÓÐÓÃÖÎÁƵĻù´¡¡£¹Å°åµÄ×éÖ¯»î¼ìºÍÓ°ÏñѧҪÁìÒÀÀµÊµÌå×éÖ¯£¬±£´æÈ¡ÑùÄÑÌâ¡¢²»¿ÉÖظ´È¡Ñù¼°ÄÑÒÔ·¢Ã÷ÔçÆÚ¸´·¢µÈÄÑÌâ¡£½üÄêÀ´£¬Ô½À´Ô½¶àµÄÑо¿Åú×¢£¬ÐÂÐ˵ÄÎÞ´´¡¢¿É¶¯Ì¬¼à²âµÄÒºÌå»î¼ìÊÖÒÕÓÐÍû³ÉΪ¿ÉÓ¦ÓÃÓÚÁÜ°ÍÁöÕï¶Ï·ÖÐÍ¡¢ÁÆЧÆÀ¹ÀºÍÔ¤ºóÆÀ¼Û¡¢¼à²â¼²²¡Ï£ÍûºÍÔçÆÚ¸´·¢µÄÓÐÓÃÒªÁì¡£


»ùÓÚѪ½¬ÓÎÀëDNAµÄ¼ì²â¸¨Öú׼ȷ·ÖÐÍ


Ö×Áö¾ßÓÐʱ¼äºÍ¿Õ¼äÉϵÄÒìÖÊÐÔ£¬²î±ðʱ¼ä¡¢²î±ð±¬·¢²¿Î»µÄÖ×Áöϸ°û°üÀ¨µÄ»ùÒò×éÐÅÏ¢¶¼²»¾¡Ïàͬ£¬ÕâЩÖ×Áöϸ°û¶ÔÖÎÁƾßÓвî±ðµÄÃô¸ÐÐÔ£¬ÕâÒ²ÊÇÖ×ÁöÕïÁƵÄÄѵãÖ®Ò»¡£

Figure 1 Ö×ÁöµÄÒìÖÊÐÔ


×éÖ¯»î¼ìÒ»Ö±ÊÇÁÜ°ÍÁöÕï¶ÏµÄ½ð±ê×¼£¬µ«±£´æÇÖÈëÐÔ¡¢È¡ÑùÄÑÌâºÍÄÑÒÔÒ»Á¬»ñµÃµÈÄÑÌâ¡£ÓÐÑо¿Ö¤ÊµÍ¨¹ý¶þ´ú²âÐò¿ÉÒÔ´ÓBϸ°ûÁÜ°ÍÁö»¼ÕßѪ½¬Öмì²âµ½ÓëÖ×ÁöÔ­·¢×éÖ¯ÏàͬµÄIgH¿Ë¡ÐÔÖØÅÅ£¬¿ÉÓÃÓÚ¸¨ÖúÁÜ°ÍÁöµÄÕï¶Ï·ÖÐÍ[1]¡£±ðµÄ£¬ÒºÌå»î¼ì¿ÉսʤÖ×ÁöÒìÖÊÐÔµÄÎÊÌ⣬Ïà±ÈÓÚ¾Ö²¿µÄ×éÖ¯»î¼ì£¬¿É»ñµÃ¸üÖÜÈ«µÄÖ×Áö»ùÒòÍ»±äÐÅÏ¢¡£

2016ÔÚScience Translational MedicineÉÏ·¢±íµÄÎÄÕÂΪctDNAÒºÌå»î¼ìÔÚÁÜ°ÍÁöÕïÁÆÖеÄÓ¦ÓÃÌṩÁËÖ÷ҪʾÀý[2]¡£ÔÚÖÎÁÆÇ°¶Ô»¼Õ߸¹¹É¹µÁÜ°ÍÁöµÄ×éÖ¯»î¼ì½«»¼Õß¹éΪ·ÇÇÖÏ®ÐÔµÄÂËÅÝÐÍÁÜ°ÍÁö£¨FL£©£¬²¢¸øÓèÀûÍ×Îôµ¥¿¹ÖÎÁÆ¡£µ«Í¬ÆÚµÄѪ½¬ctDNA¼ì²â¼ì³öÁËCARD11¼°PIM1»ùÒòÍ»±ä£¬ÕâЩͻ±äÔÚ×éÖ¯»î¼ì±ê±¾Öв¢Î´¼ì²âµ½¡£¾­ÓÉÒ»¶Îʱ¼äµÄÖÎÁƺ󣬻¼Õß·ºÆðÁËÄÍÒ©£¬Ôٴλî¼ìÈ¡ÑùµÄ²¿Î»Îª¸¹Ä¤ºóÁÜͶºÏ£¬×éÖ¯»î¼ì¼ì³öÁËCARD11¼°PIM1»ùÒòÍ»±ä£¬½«Õï¶Ï¾ÀÕýΪÇÖÏ®ÐÔµÄÂËÅÝÐÍÁÜ°ÍÁö£¨tFL£©¡£Í¬ÆÚµÄѪ½¬ctDNA¼ì²âͬÑù°üÀ¨ÕâЩͻ±ä¡£Ñо¿Õߵóö½áÂÛ¡ª¡ª¶èÐÔµÄFLºÍÇÖÏ®ÐÔµÄtFLÔÚÖÎÁÆÇ°¾Í¶¼ÒѾ­±£´æ£¬ÓÉÓÚÖ×ÁöµÄ¿Õ¼äÒìÖÊÐÔ£¬¾Ö²¿µÄ»î¼ìδÄܼì³ö¡£ÕâÏîÑо¿Ö¤ÊµÑª½¬ÖеÄctDNA¼ì²âÔÚ²¶»ñÖ×ÁöÒìÖÊÐÔÖеÄÖ÷Òª¼ÛÖµ¡£



Figure 2 ×󸹹ɹµÁÜͶºÏ»î¼ì×é֯ѧÕï¶ÏΪntFLµÄ»¼Õߣ¬ÒºÌå»î¼ì·¢Ã÷ÒþÄäÐÔÇÖÏ®ÐÔÁÜ°ÍÁöÑÇ¿Ë¡(tFL)


Ѫ½¬ÖаüÀ¨ÁËÀ´×ÔÓÚ¸÷¸ö×éÖ¯²¿Î»µÄÓÎÀëDNA£¬¸üÄÜ·´Ó¦»úÌåµÄÖ×Áö»ùÒò×éȫò¡£


»ùÓÚѪ½¬ÓÎÀëDNAµÄ¼ì²â¸¨ÖúÁÆЧ¼à²â


2017Äê½ÒÏþÔÚBloodÔÓÖ¾ÉϵÄһƪÎÄÕÂÖ¸³ö¡ª¡ªÑª½¬ÖеÄcfDNAÊÇÕï¶ÏDLBCLµÄÌåϸ°ûÍ»±äµÄ׼ȷÓÐÓûî¼ìÊÖÒÕ£¬²¢ÇÒÊÇÎÞ´´µÄ¡¢¿É¶¯Ì¬¼à²âÖ×Áö¿Ë¡Ñݱ估ÄÍÒ©¿Ë¡µÄÒªÁì[3]¡£


Davide RossiµÈÈËͨ¹ý¶ÔDLBCL»¼ÕßѪ½¬ÖеÄcfDNA¾ÙÐг¬¸ßÉî¶ÈµÄ°ÐÏò¶þ´ú²âÐò£¬¼à²âѪ½¬ÖÐÓëDLBCLÏà¹Ø»ùÒòµÄÍ»±äˮƽ£¬·¢Ã÷¶ÔR-CHOPÖÎÁÆÒªÁìÎÞÏìÓ¦µÄ»¼Õߣ¬Ñª½¬ÖÐÓëDLBCL»ùÒòÍ»±äÏà¹ØµÄcfDNAÒÀÈ»±£´æ£¨Figure 3 A¡¢B£© £»¶ø¶ÔR-CHOPÖÎÁÆÒªÁìÓÐÏìÓ¦µÄ»¼ÕßѪ½¬ÖÐÓëDLBCL»ùÒòÍ»±äÏà¹ØµÄcfDNAҲѸËÙïÔÌ­ £»µ±»¼Õß·ºÆ𸴷¢Ê±£¬Ñª½¬ÖÐÔٴμì²âµ½ÁËÏà¹ØµÄ»ùÒòÍ»±äÐÅÏ¢£¨Figure 3 C¡¢D£©¡£ÕâЩЧ¹ûÓëÏìÓ¦µÄPET/CTЧ¹ûÒ»Ö¡£


Figure 3 »ùÓÚѪ½¬cfDNAÎÞ´´ÊµÊ±¼à²âDLBCLÖеĿË¡ÑÝ»¯


Ѫ½¬ÖÐÓÎÀëctDNAº¬Á¿µÄת±äÓëÖÎÁÆЧ¹ûºÍ¼²²¡Ï£Íû¸ß¶ÈÏà¹Ø£¬²¢¿ÉÒÔʵÏÖʵʱµÄ¡¢ÎÞ´´µÄ¶¯Ì¬¼à²â¡£


»ùÓÚѪ½¬ÓÎÀëDNAµÄ¼ì²â¸¨ÖúÔ¤ºóÆÀ¹À


2018ÄêJournal of Clinical Oncology ÔÓÖ¾½ÒÏþÁËDavid M. KurtzµÈÈ˵ÄÑо¿Ð§¹û¡ª¡ªctDNAÔÚDLBCL»¼ÕßÖеÄÔ¤ºó¼ÛÖµ[4]¡£ÔÚ¸ÃÑо¿ÖУ¬¹²ÄÉÈë217ÃûÃÖÂþÐÔ´óBϸ°ûÁÜ°ÍÁö»¼Õߣ¬ÕâЩ»¼Õßƾ֤ÍâµØ±ê×¼¾ÙÐл¯ÁÆÍŽáÃâÒßÖÎÁÆ£¬¶øÑо¿Ö°Ô±¶ÔËûÃǵÄctDNAµÄ¶¯Ì¬×ª±ä¾ÙÐÐÁËÆÊÎö£¬Ð§¹ûÏÔʾ£¬ctDNAµÄˮƽÓëÎÞÊÂÎñÉúÑÄÆÚ£¨EFS£©ÒÔ¼°×ÜÉúÑÄÆÚ£¨OS£©Ò»Á¬Ïà¹Ø¡£


Ñо¿·¢Ã÷£¬ctDNA¸ßˮƽµÄ°©Ö¢»¼ÕßµÄEFSÏÔ×ŵÍÓÚctDNAµÍˮƽµÄ»¼Õß¡£ÔÚÖÎÁƵĻ¼ÕßÖУ¬¸ßˮƽµÄctDNAÍùÍùԤʾןü²îµÄOS¡£


Ñо¿ÕßÖ¸³ö£¬ÖÎÁÆÇ°µÄctDNAˮƽºÍ·Ö×Ó·´Ó¦ÊÇÅжÏÇÖÏ®ÐÔÁÜ°ÍÁöÔ¤ºóµÄ×ÔÁ¦Ö¸±ê£¬ÕâЩΣº¦ÒòËØ¿ÉÄÜ»áÖ¸µ¼Î´À´µÄ¸öÐÔ»¯Î£º¦ÆÀ¹À¡£

Figure 4 ÖÎÁÆÇ°ctDNAˮƽÓ뻼ÕßEFS¡££¨E£©Ò»ÏßÖÎÁÆ £»£¨F£©Õü¾ÈÖÎÁÆ


»ùÓÚctDNAµÄÒºÌå»î¼ì¿ÉÒÔ×ÊÖúÔçÆÚʶ±ðÓгõʼÖÎÁÆʧ°ÜΣº¦µÄÁÜ°ÍÁö»¼Õß¡£ÓÉÓڸ߶ȵÄÖ×ÁöÌØÒìÐÔ£¬¿É¶¨Á¿ÆÊÎö¼°¶¯Ì¬¼à²âµÄctDNA¼à²âÓëPET/CTÏà±È¸ü¾ßÓÐDZÔÚµÄÓÅÊÆ¡£


ÁÜ°ÍÁö¾ßÓÐÒìÖÊÐÔÇ¿¡¢Ö×Áöϸ°û¸üÒ×½øÈë¹ÇËèºÍÍâÖÜѪѭ»·ÏµÍ³µÄÌصã¡ £»ùÓÚѪ½¬ÓÎÀëDNAµÄ¸ßѸËٶȡ¢¸ßÉî¶È²âÐò½«ÊǸ¨ÖúÁÜ°ÍÁö׼ȷÕï¶Ï¡¢ÁÆЧ¼à²â¼°¸´·¢¼à²âµÄÓÐÓÃÒªÁ죬Ïà±ÈÓÚPET/CTºÍ×éÖ¯»î¼ì£¬¸üʤÔÚÎÞ´´¡¢ÎÞÉäÏßÓ°ÏìµÈÓÅÊÆ¡£Ö»¹ÜÏÖÔÚÒºÌå»î¼ìÊÖÒÕÉв»¿ÉÈ¡´ú×éÖ¯»î¼ì£¬µ«Ëü½«ÊÇ×éÖ¯»î¼ìµÄÓÐÓÃÔö²¹£¬Ò²½«½øÒ»²½Íƶ¯ÁÜ°ÍÁöÕïÁƼ°¼à²âÒªÁìµÄÉú³¤¡£


²Î¿¼ÎÄÏ×£º

1.   Roschewsk iM, Dunleavy K, Pittaluga S£¬et al. Circulating tumour DNA and CT monitoring in patients with untreated diffuse large B-cell lymphoma£ºa correlative biomarker study[J]. Lancet Oncol£¬2015£¬16(5):541-549.

2.   Scherer F, Kurtz D M, Newman A M, et al. Distinct biological subtypes and patterns of genome evolution in lymphoma revealed by circulating tumor DNA[J]. Science translational medicine, 2016, 8(364): 364ra155-364ra155.

3.   Rossi D, Diop F, Spaccarotella E, et al. Diffuse large B-cell lymphoma genotyping on the liquid biopsy[J]. Blood, 2017, 129(14):1947-1957.

4.   Kurtz D M, Scherer F, Jin M C, et al. Circulating tumor DNA measurements as early outcome predictors in diffuse large B-cell lymphoma[J]. Journal of Clinical Oncology,2018, 36(28): 2845-2853.





¡¾ÍøÕ¾µØͼ¡¿¡¾sitemap¡¿