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闄堟捣娉夊洟闃熷悎浣滅爺绌舵姤閬撴蹈娑﹀墠鑲鸿吅鐧岀殑鍩哄洜缁勫鍜屽厤鐤鐗瑰緛鍒嗘瀽

  鏃堕棿锛?019-12-15   鏉ユ簮锛氶檮灞炶偪鐦ゅ尰闄↑/td>   鐐瑰嚮锛?8
 

鑲鸿吅鐧孅/span>锛圏/span>LUAD锛夋槸鏈€甯歌鐨勮偤鐧岀粍缁囧浜氬瀷锛屽钩鍧?骞寸敓瀛樼巼涓?5锛呫€傜浉姣斾箣涓嬶紝LUAD鐨勬蹈娑﹀墠闃舵锛屼緥濡傚師浣嶈吅鐧岋紙AIS锛夊拰寰蹈娑﹁吅鐧岋紙MIA锛夛紝鍦ㄦ墜鏈垏闄ゅ悗5骞村唴涓嶅鍙戠殑姣斾緥鎺ヨ繎100锛呫€侫IS鐨勫畾涔変负鈮?cm鐨勬棤娴告鼎鎬ц吅鐧岋紝鑰孧IA鏄墹3cm鐨勨墹5mm娴告鼎鎬ц吅鐧屻€傚敖绠′竴浜涢噸鐐圭爺绌跺凡缁忕‘瀹氫簡AIS鍜孧IA涓偤鐧岄┍鍔ㄧ▼搴忕殑绐佸彉锛屼絾瀵逛簬椹卞姩杩欎簺鐥呭彉鍚戜镜琚€UAD鍙戝睍鐨勫垎瀛愪簨浠朵粛鐒剁己涔忔繁鍏ョ殑浜嗚В銆傚師浣嶈吅鐧屽拰寰蹈娑﹁吅鐧屾槸鑲鸿吅鐧岀殑娴告鼎鍓嶇梾鍙橈紝鑰屼汉浠?/span>瀵硅繖浜涚梾鍙樼殑鍩哄洜缁勫拰鍏嶇柅瀛︾壒寰佷簡瑙e緱寰堝皯銆侟/span>

杩戞棩锛孅/span>澶嶆棪澶у闄勫睘鑲跨槫鍖婚櫌闄堟捣娉堻/span>鏁欐巿鍥㈤槦鍜屽搱浣涘ぇ瀛﹀尰瀛﹂櫌Matthew Meyerson鍥㈤槦鍚堜綔锛孅/span>鍦?/span>銆婅嚜鐒堕€氳銆嬶紙Nature Communications锛堻/span>涓婂彂琛ㄦ枃绔燑/span>鈥淈/span>Genomic and immune profiling of pre-invasive lung adenocarcinoma鈥滭/span>銆傜爺绌跺24涓師浣嶈吅鐧屻€?4涓井娴告鼎鎬ц吅鐧屽拰99涓蹈娑︽€ц吅鐧岃繘琛屽叏澶栨樉瀛愬拰杞綍缁勬祴搴廃/span>锛孅/span>鍙戠幇EGFR銆丷BM10銆丅RAF銆丒RBB2銆乀P53銆並RAS銆丮AP2K1鍜孅/span>MET鍦ㄥ師浣嶈吅鐧孅/span>/寰蹈娑︽€х檶涓负鏄捐憲绐佸彉鍩哄洜锛屾彮绀轰簡鍦ㄨ偪鐦よ繘灞曡繃绋嬩腑棰戠巼鏄捐憲澧炲姞鐨勫熀鍥犵粍鏀瑰彉鐨勭被鍒紝鍖呮嫭TP53绐佸彉銆佽噦绾ф嫹璐濇暟鏀瑰彉鍜孒LA鏉傚悎缂哄け銆傚厤鐤蹈娑︿笌6p鍙锋煋鑹蹭綋鐨勬嫹璐濇暟鍙樺寲鏈夊叧锛岃〃鏄?p鏌撹壊浣撲簨浠朵笌鑲跨槫鍏嶇柅鐜涔嬮棿涔熷瓨鍦ㄤ竴瀹氳仈绯汇€侟/span>

鐮旂┒鍥㈤槦鍦?/span>AIS鍜孧IA鏍囨湰涓壌瀹氫簡8涓樉钁楃獊鍙樼殑鍩哄洜锛屽寘鎷?/span>EGFR銆丷BM10銆丅RAF銆丒RBB2銆乀P53銆並RAS銆丮AP2K1鍜孅/span>MET锛岃繖浜涘熀鍥犲厛鍓嶅潎琚?/span>TCGA鐨凩UAD闃熷垪涓姤閬撹繃銆傚湪璇ョ爺绌剁殑娴告鼎鎬ц吅鐧岀梾渚嬩腑锛孅/span>EGFR銆乀P53銆丷B1鍜孅/span>KRAS涓烘樉钁楃獊鍙樸€傚悓鏃讹紝鐮旂┒鍥㈤槦鍦?/span>AIS鎴朚IA鏍峰搧涓彂鐜颁簡MDM2銆丮YC銆乀ERT銆並RAS銆丯KX2-1鍜孅/span>CDK6鐨勬墿澧烇紝骞朵笖鍦?/span>闄勫睘鑲跨槫鍖婚櫌鑲鸿吅鐧屾偅鑰呴槦鍒椾腑鍙戠幇浜咟/span>RIT1鐨勬柊鍨嬫墿澧炪€俁NA-seq鍒嗘瀽鎻ず浜哅IA鏍峰搧涓殑RET铻嶅悎浠ュ強娴告鼎鎬ц吅鐧屼腑鐨凙LK鍜孯OS1铻嶅悎銆傛蹈娑︽€ц吅鐧屼笌AIS/MIA绐佸彉棰戠巼宸紓鏈€澶х殑鏄疶P53绐佸彉锛?8%锛夛紝鍏舵鏄疎GFR鍜孯B1绐佸彉銆備笌AIS/MIA鐩告瘮锛屾蹈娑︽€ц吅鐧岀殑鑲跨槫绐佸彉璐熻嵎锛圱MB锛夋樉钁楁洿楂橈紝APOBEC绐佸彉鐗瑰緛娲绘€ф洿楂橈紝鏌撹壊浣撹噦绾у埆浜嬩欢鍙戠敓棰戠巼涔熸洿楂樸€侟/span>


浜虹櫧缁嗚優鎶楀師锛圏/span>HLA锛夌瓑浣嶅熀鍥犵殑涓㈠け宸茶纭畾涓鸿偤鐧岀殑娼滃湪鍏嶇柅閫冮€告満鍒躲€傚湪璇?/span>鐮旂┒涓紝鐮旂┒鍥㈤槦鍙戠幇3.1锛呯殑AIS/MIA鍜?6.7锛呯殑娴告鼎鎬ц吅鐧屾爣鏈腑鍑虹幇HLA鏉傚悎涓㈠け锛圠OH锛夈€備笌娴告鼎鍓嶇粍鐩告瘮锛屾蹈娑︾粍涓璈LA LOH鐨勯鐜囨樉鐫€澧炲姞锛團isher绮剧‘妫€楠岋紝p <0.01锛夎〃鏄庯紝HLA绛変綅鍩哄洜缂哄け鍦ㄨ偪鐦ゅ彂灞曡繃绋嬩腑璧峰埌涓€瀹氱殑浣滅敤銆傝繘涓€姝ョ爺绌跺彂鐜帮紝娴告鼎鎬ц吅鐧屼腑绾?0锛呯殑HLA LOH浜嬩欢涓?p鏌撹壊浣撲涪澶辨湁鍏炽€傛湁瓒g殑鏄紝鐮旂┒鍥㈤槦鍙戠幇6p鐨勬墿澧炰笌T缁嗚優涓板害鏄捐憲鐩稿叧锛圡ann-Whitney U妫€楠岋紝p = 0.038锛屽浘3锛夛紝骞朵笖鍦ㄥ垎鏋怋缁嗚優娴告鼎涓?p CNA鐩稿叧鏃朵篃瑙傚療鍒拌繖绉嶈秼鍔裤€傜爺绌迭/span>鍥㈤槦闅忓悗浣跨敤TCGA LUAD鐮旂┒缁勭殑鏍锋湰娴嬭瘯浜嗗厤鐤蹈娑︿笌澶ф煋鑹蹭綋鎷疯礉鏁版敼鍙樼殑鐩稿叧鎬э紝瑙傚療鍒板湪鎺у埗TMB鍜屾暣浣撻潪鏁村€嶆€х▼搴﹀悗锛岀櫧缁嗚優鍒嗘暟涓?p鏌撹壊浣揅NA鐨勭浉鍏虫€ф渶鏄捐憲锛坧 = 0.0030锛宑oef = -0.74锛?5锛匔I锛?1.23鑷?0.25锛夛紝鍏舵鏄?q锛坧 = 0.0033锛宑oef = -0.60锛?5锛匔I锛?1鑷?0.2锛夊拰19p CNA锛坧 = 0.0047锛岀郴鏁? 0.53锛?5锛匔I锛?.16鑷?.9锛夈€?p鍜?q CNA鍦?/span>闄勫睘鑲跨槫鍖婚櫌鐮旂┒闃熷垪涓樉绀轰粠AIS/MIA鍒癓UAD鐨勯鐜囨樉鐫€澧炲姞锛團isher绮剧‘妫€楠岋紝p <0.001锛夈€侟/span>


璇?/span>鏂囨彮绀轰簡娴告鼎鍓岦/span>/娴告鼎鎬ц偤鐧岀殑鍩哄洜缁勫拰鍏嶇柅瀛︾壒寰併€侟/span>71锛呯殑AIS鍜孧IA鎮h€呮惡甯﹁嚦灏戜竴涓湪RTK/RAS/RAF閫氳矾涓厛鍓嶉壌瀹氱殑鐧岀棁鍩哄洜绐佸彉锛岃繖涓庢蹈娑︽€ц偤鑵虹檶涓殑鑷寸檶椹卞姩浜嬩欢楂樺害鐩镐技銆侟/span>璇ョ爺绌朵篃鎻ず浜咟/span>TP53鏄偤鐧屾蹈娑︾殑鍏抽敭浠嬭川銆傚厛鍓嶅湪Barrett椋熺涓繘琛岀殑鐮旂┒琛ㄦ槑锛孴P53鍦ㄩ閬撹吅鐧屽墠浣撲腑杈冩棭鍙戠敓锛岀劧鍚庢槸鑷寸檶鎬ф墿澧炪€俆P53鍦ㄥ師浣嶈偤槌炵檶涓篃缁忓父鍙戠敓绐佸彉锛岃繖鏄碁鐘剁粏鑳炵檶鐨勭檶鍓嶇梾鍙楛/span>銆傝鏂囨樉绀轰簡鑷寸檶鐨勯┍鍔ㄧ獊鍙樼殑楂橀鐜囷紝浣嗗湪AIS/MIA涓璗P53绐佸彉鐨勯鐜囪緝浣庛€傚厛鍓嶇殑鐮旂┒琛ㄦ槑锛孅/span>TP53绐佸彉涓庣檶鐥囩殑娼滃湪渚佃鍔熻兘鐩稿叧锛屾湰鏂囪繕琛ㄦ槑浜咟/span>TP53绐佸彉涓庢煋鑹蹭綋鐨勯潪鏁村€嶆€у瘑鍒囩浉鍏筹紝涓嶵GCA鐨勬渶鏂扮爺绌朵竴鑷淬€傞壌浜庡厛鍓嶆湁鍏抽潪鏁村€嶆€т笌鍏嶇柅娴告鼎鍑忓皯鐩稿叧鐨勬姤閬擄紝鐮旂┒鍥㈤槦鎻愬嚭浜嗙壒瀹氭煋鑹蹭綋鐨勬嫹璐濇暟鍙樺寲鍙兘褰卞搷鑲跨槫寰幆澧冪殑鍙兘鎬э紝鎻愪緵浜嗗鑲烘伓鎬ц偪鐦ょ敓鐗╁鐨勬柊瑙佽В锛屽鐤剧梾鐩戞祴鍜岄鍚庝互鍙婃湭鏉ョ殑娌荤枟骞查鍏锋湁閲嶈鎰忎箟銆侟/span>

鍘熸枃閾炬帴锛欬/span>https://www.nature.com/articles/s41467-019-13460-3.pdf

 
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