{"id":37067,"date":"2024-06-14T12:00:50","date_gmt":"2024-06-14T12:00:50","guid":{"rendered":"https:\/\/zydq.1006ss.com\/?p=37067"},"modified":"2024-06-14T12:00:50","modified_gmt":"2024-06-14T12:00:50","slug":"%e6%96%b0%e7%83%ad%e7%82%b9%ef%bc%9a%e4%b8%ad%e6%80%a7%e7%b2%92%e7%bb%86%e8%83%9e%e8%83%9e%e5%a4%96%e9%99%b7%e9%98%b1%e7%9b%b8%e5%85%b3%e6%b3%9b%e7%99%8c%e5%88%86%e6%9e%90%e5%8f%af%e5%8f%918-%ef%bc%81","status":"publish","type":"post","link":"http:\/\/zydq.1006ss.com\/?p=37067","title":{"rendered":"\u65b0\u70ed\u70b9\uff1a\u4e2d\u6027\u7c92\u7ec6\u80de\u80de\u5916\u9677\u9631\u76f8\u5173\u6cdb\u764c\u5206\u6790\u53ef\u53d18 \uff01"},"content":{"rendered":"

\u5bfc\u8bed<\/p>\n

\u4e2d\u6027\u7c92\u7ec6\u80de\u5f62\u6210\u79f0\u4e3a\u4e2d\u6027\u7c92\u7ec6\u80de\u80de\u5916\u9677\u9631 (NETs) \u7684\u7ec6\u80de\u5916\u7f51\u72b6\u7ed3\u6784\u3002\u65b0\u51fa\u73b0\u7684\u8bc1\u636e\u8868\u660e\uff0c\u764c\u75c7\u53ef\u4ee5\u8bf1\u5bfc NET \u7684\u5f62\u6210\uff1b\u7136\u800c\uff0c\u5c1a\u672a\u5b8c\u5168\u4e86\u89e3 NETs \u5982\u4f55\u5f71\u54cd\u764c\u75c7\u751f\u7269\u5b66\uff0c\u5e76\u4e14\u5c1a\u672a\u5c31\u5176\u4fc3\u764c\u6216\u6297\u764c\u4f5c\u7528\u8fbe\u6210\u5171\u8bc6\u3002<\/p>\n

\u80cc\u666f\u4ecb\u7ecd\u4eca\u5929\u5c0f\u7f16\u4e3a\u5927\u5bb6\u5e26\u6765\u7684\u8fd9\u7bc7\u6587\u7ae0\uff0c\u63a2\u7d22\u548c\u8ba8\u8bba\u4e86 NET \u5bcc\u96c6\u3001NET \u76f8\u5173\u57fa\u56e0\u8c03\u63a7\u6a21\u5f0f\uff0c\u4ee5\u53ca NET \u5bf9 22 \u79cd\u4e3b\u8981\u4eba\u7c7b\u764c\u75c7\u7c7b\u578b\u7684\u5927\u7ea6 8,000 \u540d\u60a3\u8005\u7684\u9884\u540e\u5f71\u54cd\u3002\u6587\u7ae0\u53d1\u8868\u5728\u300aFrontiers in Immunology\u300b\u4e0a\uff0c\u5f71\u54cd\u56e0\u5b50\u4e3a8.786\uff0c\u6587\u7ae0\u9898\u76ee\u4e3a\uff1aPan-Cancer Analysis Reveals a Distinct Neutrophil Extracellular Trap-Associated Regulatory Pattern\u3002<\/p>\n

\u6570\u636e\u4ecb\u7ecd\u672c\u7814\u7a76\u4ece TCGA \u6570\u636e\u95e8\u6237\u7f51\u7ad9\u4e0b\u8f7d\u4e86 22 \u79cd\u4eba\u7c7b\u764c\u75c7\u7c7b\u578b\u7684\u5927\u7ea6 10,000 \u540d\u60a3\u8005\u7684 FPKM \u6807\u51c6\u5316 mRNA \u8868\u8fbe\u8c31\u548c\u4e34\u5e8a\u7279\u5f81\u3002\u53bb\u9664\u6279\u6b21\u6548\u5e94\u540e\uff0c\u4ece UCSC Xena \u4e0b\u8f7d\u5305\u542b\u5927\u7ea6 10,000 \u4e2a\u6837\u672c\u7684 PanCan TCGA \u8868\u8fbe\u96c6\u3002BRCA \u86cb\u767d\u8868\u8fbe\u8c31\u662f\u4ece CPTAC\u4e0b\u8f7d\u7684\u3002\u4ece\u767b\u5f55\u53f7\u4e3a GSE78220 \u548c GSE91061 \u7684 GEO \u6570\u636e\u96c6\u4e0b\u8f7d 2 \u4e2a\u8180\u80f1\u764c\u6837\u672c\u548c 1 \u4e2a\u76ae\u80a4\u764c\u6837\u672c\u7684\u57fa\u56e0\u8868\u8fbe\u9635\u5217\u3002\u6280\u672f\u8def\u7ebf\u672c\u7814\u7a76\u6280\u672f\u8def\u7ebf\u5982\u56fe\u6240\u793a\u3002<\/p>\n

\u7ed3\u679c\u89e3\u679001\u6cdb\u764cNET\u76f8\u5173\u5931\u8c03\u7684\u5b9a\u4e49\u4e3a\u4e86\u5bf9\u4e0d\u540c\u764c\u75c7\u7c7b\u578b\u7684 NET \u8fdb\u884c\u6982\u8ff0\uff0c\u672c\u7814\u7a76\u5b9a\u4e49\u4e86 22 \u79cd\u764c\u75c7\u4e2d 23 \u4e2a\u57fa\u56e0\u7684\u6cdb\u764c NET \u7279\u5f81\u3002\u4e3a\u4e86\u91cf\u5316\u6d78\u6da6\u7684 NET\uff0c\u672c\u7814\u7a76\u8ba1\u7b97\u4e86\u6bcf\u79cd\u764c\u75c7\u7c7b\u578b\u7684 NET \u7b7e\u540d\uff08NET \u5206\u6570\uff09\u7684 GSVA \u5bcc\u96c6\u5206\u6570\u3002\u4e0d\u540c\u80bf\u7624\u7c7b\u578b\u7684 NET \u8bc4\u5206\u5dee\u5f02\u5f88\u5927\uff08\u56fe 1A\uff09\uff0c\u5934\u9888\u764c (HNSC) \u548c\u4e24\u79cd\u7c7b\u578b\u7684\u80ba\u764c\uff08LUAD\u3001LUSC\uff09\u6210\u4e3a NET \u5bcc\u96c6\u7684\u524d\u4e09\u79cd\u764c\u75c7\u7c7b\u578b\u3002<\/p>\n

\u63a5\u4e0b\u6765\u672c\u7814\u7a76\u6bd4\u8f83\u4e86 PANCAN \u6570\u636e\u96c6\u4e2d\u80bf\u7624\u548c\u526f\u80bf\u7624\u7ec4\u7ec7\u4e0e\u4e2a\u4f53\u764c\u75c7\u7c7b\u578b\u4e4b\u95f4 NETs \u76f8\u5173\u57fa\u56e0\u7684\u8868\u8fbe\u6c34\u5e73\uff0c\u5e76\u53d1\u73b0\u4e86\u4e0d\u540c\u764c\u75c7\u7c7b\u578b\u548c\u57fa\u56e0\u7684\u5931\u8c03\u6a21\u5f0f\u3002\u5176\u4e2d CAT\u3001CTSG\u3001LTF\u3001LCP1\u3001S100A8 \u548c S100A9 \u5931\u8c03\u6700\u4e25\u91cd\uff1bLUSC\u3001LUAD\u3001GBM\u3001ESCA\u3001CHOL \u548c CESC \u663e\u793a\u51fa\u5931\u8c03\u7684 NET \u57fa\u56e0\u7684\u6700\u9ad8\u79ef\u7d2f\uff08\u56fe 1B\uff09\u3002\u6b64\u5916\uff0c\u706b\u5c71\u56fe\u663e\u793a\u5927\u591a\u6570 NET \u76f8\u5173\u57fa\u56e0\u5728\u6cdb\u764c\u5206\u6790\u4e2d\u4e0a\u8c03\uff08\u56fe 1C\uff09\u3002<\/p>\n<\/p>\n

\u56fe 1<\/p>\n

NET \u5f62\u6210\u662f\u4e00\u4e2a\u590d\u6742\u7684\u8c03\u8282\u8fc7\u7a0b\uff0c\u6d89\u53ca\u4e00\u7cfb\u5217\u751f\u7269\u5b66\u6b65\u9aa4\u548c\u9057\u4f20\u76f8\u4e92\u4f5c\u7528\uff1b\u56e0\u6b64\uff0c\u672c\u7814\u7a76\u51b3\u5b9a\u7814\u7a76 NET \u57fa\u56e0\u7684\u76f8\u4e92\u4f5c\u7528\u6a21\u5f0f\u3002\u4e3a\u6b64\uff0c\u672c\u7814\u7a76\u5728 STING \u6570\u636e\u5e93\u4e2d\u68c0\u67e5\u4e86 NET \u57fa\u56e0\u7684\u6f5c\u5728\u86cb\u767d\u8d28-\u86cb\u767d\u8d28\u76f8\u4e92\u4f5c\u7528\u7f51\u7edc (PPI)\uff0c\u5e76\u53d1\u73b0\u4e86\u4e00\u4e2a\u590d\u6742\u7684\u76f8\u4e92\u4f5c\u7528\u7f51\u7edc\uff0c\u8868\u660e\u7531 NET \u5f62\u6210\u7684\u5171\u540c\u8c03\u8282\u7f51\u7edc\uff08\u56fe 1D\uff09\u3002\u603b\u4e4b\uff0c\u8fd9\u4e9b\u7ed3\u679c\u63ed\u793a\u4e86\u5404\u79cd\u764c\u75c7\u7c7b\u578b\u4e2d NET \u5f62\u6210\u7684\u5931\u8c03\u6a21\u5f0f\u3002<\/p>\n

02NET\u5206\u6570\u4e0e\u4e3b\u8981\u764c\u75c7\u6807\u5fd7\u5bc6\u5207\u76f8\u5173\uff0c\u5c24\u5176\u662f\u708e\u75c7\u53cd\u5e94\u672c\u7814\u7a76\u8fdb\u4e00\u6b65\u63a2\u8ba8\u4e86 NET \u8bc4\u5206\u4e0e\u51e0\u4e2a\u5173\u952e\u764c\u75c7\u6807\u5fd7\u4e4b\u95f4\u7684\u5173\u7cfb\uff0c\u5305\u62ec\u8840\u7ba1\u751f\u6210\u3001\u6297\u7ec6\u80de\u51cb\u4ea1\u3001\u975e\u6574\u500d\u4f53\u3001\u4e0a\u76ae\u95f4\u5145\u8d28\u8f6c\u5316 (EMT)\u3001\u7cd6\u9175\u89e3\u3001\u7f3a\u6c27\u3001\u708e\u75c7\u53cd\u5e94\u548c\u7ec6\u80de\u589e\u6b96\u3002\u672c\u7814\u7a76\u6bd4\u8f83\u4e86 NET \u548c\u6807\u5fd7\u5206\u6570\u4e4b\u95f4\u7684 Pearson \u76f8\u5173\u6027\uff0c\u8fd9\u4e9b\u5206\u6570\u7531\u57fa\u56e0\u96c6\u7684 ssGSEA \u5206\u6570\u8868\u793a\u3002\u516b\u4e2a\u6807\u5fd7\u4e2d\u6709\u516d\u4e2a\u4e0e NET \u5206\u6570\u5448\u6b63\u76f8\u5173\u3002\u5728\u8fd9\u4e00\u7ec4\u4e2d\uff0c\u708e\u75c7\u53cd\u5e94\u663e\u793a\u51fa\u6700\u9ad8\u7684\u76f8\u5173\u6027\uff0c\u5728 22 \u79cd\u764c\u75c7\u7c7b\u578b\u4e2d\uff0c\u6709 14 \u79cd\u7684 R \u503c\u8d85\u8fc7 0.6\u3002\u76f8\u6bd4\u4e4b\u4e0b\uff0c\u589e\u6b96\u548c\u975e\u6574\u500d\u4f53\u4e0e 20 \u79cd\u764c\u75c7\u7c7b\u578b\u7684 NET \u8bc4\u5206\u5448\u8d1f\u76f8\u5173\uff08\u56fe 2A\uff09\u3002\u4f7f\u7528 MCPcounters\uff0c\u672c\u7814\u7a76\u5bf9 10 \u79cd\u514d\u75ab\u548c\u57fa\u8d28\u7ec6\u80de\u6210\u5206\u8fdb\u884c\u4e86\u53cd\u5377\u79ef\uff0c\u53d1\u73b0 NET \u8bc4\u5206\u4e0e\u5927\u591a\u6570\u764c\u75c7\u7c7b\u578b\u4e2d\u7684\u5355\u6838\u7ec6\u80de\u3001\u4e2d\u6027\u7c92\u7ec6\u80de\u548c\u9ad3\u6837\u6811\u7a81\u72b6\u7ec6\u80de\u4e4b\u95f4\u5b58\u5728\u6b63\u76f8\u5173\uff1b\u7136\u800c\uff0c\u672c\u7814\u7a76\u53d1\u73b0 NET \u8bc4\u5206\u4e0e\u7ec6\u80de\u6bd2\u6027 T \u7ec6\u80de\u3001NK \u7ec6\u80de\u6216 B \u7ec6\u80de\u4e4b\u95f4\u6ca1\u6709\u663e\u8457\u5173\u8054\uff08\u56fe 2A\uff09\u3002\u672c\u7814\u7a76\u8fd8\u6bd4\u8f83\u4e86\u6bcf\u79cd\u764c\u75c7\u7c7b\u578b\u7684 NET-high \u548c NET-low \u7ec4\u4e4b\u95f4\u51e0\u79cd\u7c7b\u578b\u514d\u75ab\u7ec6\u80de\u7684\u8d8b\u5316\u56e0\u5b50\u8c31\u3002\u706b\u5c71\u56fe\u663e\u793a\uff0cNET-high \u7ec4\u8d8b\u5316\u56e0\u5b50\u7684\u8868\u8fbe\u6c34\u5e73\u666e\u904d\u8f83\u9ad8\uff0c\u5e76\u4e14\u5728\u6240\u6709\u764c\u75c7\u7c7b\u578b\u4e2d\u5bf9\u7c92\u7ec6\u80de\u548c\u767d\u7ec6\u80de\u7684\u8d8b\u5316\u4f5c\u7528\u53ef\u80fd\u66f4\u5f3a\uff0c\u8868\u660e NETs \u4e0e\u764c\u75c7\u514d\u75ab\u7ec6\u80de\u4e4b\u95f4\u5b58\u5728\u590d\u6742\u7684\u8c03\u8282\u7f51\u7edc\uff08\u56fe2B )\u3002<\/p>\n

\u56fe 2<\/p>\n

\u7136\u540e\uff0c\u672c\u7814\u7a76\u5728\u63a5\u53d7\u6297 PD1 \u6cbb\u7597\u7684 3 \u4e2a\u72ec\u7acb\u961f\u5217\u4e2d\u6bd4\u8f83\u4e86\u53cd\u5e94\u7ec4\uff08PR\u3001CR\uff09\u548c\u65e0\u53cd\u5e94\u7ec4\uff08SD\u3001PD\uff09\u4e4b\u95f4\u7684 NET \u8bc4\u5206 \u3002\u4e0e NET \u8bc4\u5206\u548c\u514d\u75ab\u68c0\u67e5\u70b9\u57fa\u56e0\u4e4b\u95f4\u7684\u76f8\u5173\u6027\u4e00\u81f4\uff0c3 \u4e2a\u961f\u5217\u4e2d\u6709 2 \u4e2a\u7684\u65e0\u53cd\u5e94\u7ec4\u7684 NET \u8bc4\u5206\u663e\u8457\u66f4\u9ad8\uff08\u56fe 2C\uff09\u3002\u8fd9\u4e9b\u53d1\u73b0\u5f3a\u8c03 NETs \u4f5c\u4e3a\u5173\u952e\u764c\u75c7\u76f8\u5173\u751f\u7269\u8fc7\u7a0b\u548c\u80bf\u7624\u76f8\u5173\u514d\u75ab\u5b66\u7684\u4e2d\u592e\u8c03\u8282\u5668\uff0c\u5e76\u8868\u660e NETs \u53ef\u80fd\u9884\u6d4b\u514d\u75ab\u68c0\u67e5\u70b9\u6291\u5236\u7ed3\u679c\u300203NET\u5bf9\u4e0d\u540c\u764c\u75c7\u7c7b\u578b\u5177\u6709\u4e0d\u540c\u7684\u9884\u540e\u5f71\u54cd\u4e3a\u4e86\u7814\u7a76 NET \u8bc4\u5206\u5bf9\u764c\u75c7\u9884\u540e\u7684\u5f71\u54cd\uff0c\u672c\u7814\u7a76\u5206\u6790\u4e86\u6765\u81ea 22 \u79cd\u4e0d\u540c\u764c\u75c7\u7c7b\u578b\u7684 8,059 \u540d\u60a3\u8005\u7684\u6570\u636e\u3002\u8fd9\u4e9b\u60a3\u8005\u6839\u636e NET \u8bc4\u5206\u5206\u4e3a 4 \u7c7b\uff0c\u5e76\u901a\u8fc7 Kaplan-Meier \u5206\u6790\u6bd4\u8f83\u4ed6\u4eec\u7684\u751f\u5b58\u7387\u3002NET \u8bc4\u5206\u6700\u9ad8\u5206\u4f4d\u6570\u7684\u764c\u75c7\u60a3\u8005\u9884\u540e\u6700\u597d\uff0c\u800c\u6700\u4f4e\u5206\u4f4d\u6570\u7684\u60a3\u8005\u9884\u540e\u6700\u5dee\uff08\u56fe 3A\uff09\u3002\u7531\u4e8e\u6240\u9009\u764c\u75c7\u7c7b\u578b\u5305\u542b\u975e\u5e38\u4e0d\u540c\u7c7b\u578b\u7684\u6076\u6027\u80bf\u7624\uff0c\u56e0\u6b64\u672c\u7814\u7a76\u968f\u540e\u5206\u522b\u8bc4\u4f30\u4e86\u6bcf\u79cd\u764c\u75c7\u7c7b\u578b\u7684 NET \u76f8\u5173\u751f\u5b58\u7387\u3002\u5728\u524d\u5217\u817a\u764c (PAAD)\u3001\u98df\u9053\u764c (ESCA)\u3001\u76ae\u80a4\u764c (SKCM)\u3001\u8089\u7624 (SARC)\u3001\u4e73\u817a\u764c (BRCA) \u548c\u7ed3\u80a0\u764c (COAD) \u4e2d\uff0c\u8f83\u9ad8\u7684 NET \u8bc4\u5206\u4e0e\u6709\u5229\u7684\u751f\u5b58\u76f8\u5173\u3002\u76f8\u6bd4\u4e4b\u4e0b\uff0c\u5728\u80f0\u817a\u764c (PDAC)\u3001\u80ba\u9cde\u764c (LUSC)\u3001\u80f6\u8d28\u6bcd\u7ec6\u80de\u7624 (GBM)\u3001\u4f4e\u7ea7\u522b\u80f6\u8d28\u7624 (LGG)\u3001\u5375\u5de2\u764c (OV)\u3001\u80c3\u764c (STAD) \u548c\u8180\u80f1\u764c (BLCA) \u4e2d\uff0c\u66f4\u9ad8NET \u5206\u6570\u4e0e\u8f83\u5dee\u7684\u751f\u5b58\u7387\u76f8\u5173\uff08\u56fe 3B\uff09\u3002\u8fd9\u4e9b\u7ed3\u679c\u8868\u660e\u5728\u4e0d\u540c\u7684\u764c\u75c7\u7c7b\u578b\u4e2d\u5b58\u5728\u4e24\u79cd NET \u76f8\u5173\u7684\u751f\u5b58\u6a21\u5f0f\u3002<\/p>\n

\u56fe 3<\/p>\n

04\u786e\u5b9a\u5b58\u6d3b\u7387\u9ad8\u6216\u4f4e\u7684\u764c\u75c7\u4e2dNET\u76f8\u5173\u7684\u8c03\u8282\u6a21\u5f0f<\/p>\n

\u4e3a\u4e86\u89e3\u91ca\u4e0d\u540c\u764c\u75c7\u7c7b\u578b\u7684\u4e0d\u540c NET \u76f8\u5173\u7ed3\u679c\uff0c\u672c\u7814\u7a76\u5b9a\u4e49\u4e86\u4e0e\u6bcf\u79cd\u764c\u75c7\u7c7b\u578b\u7684 NET \u8bc4\u5206\u5bc6\u5207\u76f8\u5173\u7684 NET \u76f8\u5173\u57fa\u56e0 (NRG) \u7ec4\u3002\u603b\u5171\u786e\u5b9a\u4e86 35,034 \u4e2a NET-NRG \u5bf9\uff0c\u5176\u4e2d 15,476 \u4e2a\u5c5e\u4e8e NET \u76f8\u5173\u751f\u5b58\u7387\u8f83\u9ad8\u7684\u764c\u75c7\uff0c19,558 \u4e2a\u5c5e\u4e8e NET \u76f8\u5173\u751f\u5b58\u7387\u8f83\u5dee\u7684\u764c\u75c7\uff08\u56fe 4A\uff09\u3002\u5728\u6bcf\u4e2a\u751f\u5b58\u7ec4\u4e2d\u8d85\u8fc7 5 \u79cd\u764c\u75c7\u7c7b\u578b\u4e2d\u9274\u5b9a\u51fa\u7684 NET-NRG \u5bf9\u88ab\u8fdb\u4e00\u6b65\u5b9a\u4e49\u4e3a\u6838\u5fc3 NET-NRG \u5bf9\uff0cNET\u76f8\u5173\u751f\u5b58\u826f\u597d\u7684\u764c\u75c7\u7c7b\u578b\u4e2d\u6709533\u5bf9NET-NRG\u5bf9\uff0cNET\u751f\u5b58\u8f83\u5dee\u7684\u764c\u75c7\u7c7b\u578b\u4e2d\u6709709\u5bf9NET-NRG\u5bf9\uff0c\u5176\u4e2d411 \u5bf9\u91cd\u53e0\uff08\u56fe 4B\uff09\u3002<\/p>\n

\u4e3a\u4e86\u8fdb\u4e00\u6b65\u63a2\u7d22 NRG \u5931\u8c03\uff0c\u672c\u7814\u7a76\u91cd\u65b0\u68c0\u67e5\u4e86 HepG2 \u548c MHCC97H \u764c\u7ec6\u80de\u7684 RNA \u6570\u636e\u5728-\u4e4b\u524d\u7684\u7814\u7a76\u4e2d\u6709\u6ca1\u6709 NET \u523a\u6fc0\u3002\u8be5\u5206\u6790\u8868\u660e\uff0c\u5728 NET \u523a\u6fc0\u540e\uff0c\u5177\u6709\u826f\u597d\u6216\u4e0d\u826f\u5b58\u6d3b\u7387\u7684 NRG \u4ee5\u53ca\u6240\u6709 NRG \u90fd\u88ab\u4e0a\u8c03\uff08\u56fe 4C\u3001D\uff09\u3002<\/p>\n<\/p>\n

\u56fe 4<\/p>\n

\u4e24\u7ec4 NET-NRG \u5bf9\u5177\u6709\u4e0d\u540c\u7684\u751f\u7269\u5b66\u529f\u80fd\u3002\u4e24\u7ec4 NET-NRG \u5bf9\u7684 KEGG \u6ce8\u91ca\u8868\u660e\uff0c\u5177\u6709\u826f\u597d NET \u76f8\u5173\u751f\u5b58\u7387\u7684\u764c\u75c7\u7c7b\u578b\u4e2d\u7684 NET-NRG \u5bf9\u5bcc\u96c6\u5728Rap1\u3001\u9798\u8102\u4fe1\u53f7\u548c\u677e\u5f1b\u7d20\u4fe1\u53f7\u901a\u8def\u3002\u5bf9\u4e8e NET-NRG \u5bf9\uff0c\u5728 NET \u76f8\u5173\u751f\u5b58\u7387\u8f83\u5dee\u7684\u764c\u75c7\u4e2d\uff0c\u5bcc\u96c6\u5728\u5c40\u7076\u6027\u7c98\u8fde\u548c ECM-\u53d7\u4f53\u76f8\u4e92\u4f5c\u7528\u3002\u5bf9\u4e8e\u5171\u4eab\u7684 NET-NRG \u5bf9\uff0c\u5bcc\u96c6\u5728\u7ec6\u80de\u56e0\u5b50\u76f8\u5173\u901a\u8def\u548c\u91d1\u9ec4\u8272\u8461\u8404\u7403\u83cc\u611f\u67d3\uff08\u56fe 4E-G\uff09\u3002\u8fd9\u4e9b\u6a21\u5f0f\u53ef\u80fd\u5bf9 NET \u76f8\u5173\u7684\u751f\u5b58\u4ea7\u751f\u81f3\u5173\u91cd\u8981\u7684\u5f71\u54cd\u3002<\/p>\n

05NET\u76f8\u5173\u7684\u8c03\u63a7\u6a21\u5f0f\u4e0e\u9884\u540e\u76f8\u5173\u7684\u5171\u8868\u8fbe\u57fa\u56e0\u7c07\u6709\u5173\u672c\u7814\u7a76\u5047\u8bbe NET \u76f8\u5173\u57fa\u56e0\u5305\u62ec 2 \u7ec4\uff1a\u5177\u6709\u4fc3\u80bf\u7624\u4f5c\u7528\u7684\u57fa\u56e0\u548c\u5177\u6709\u6297\u80bf\u7624\u4f5c\u7528\u7684\u57fa\u56e0\u3002\u4e3a\u4e86\u63a2\u7d22\u8fd9\u79cd\u53ef\u80fd\u6027\uff0c\u672c\u7814\u7a76\u8bc4\u4f30\u4e86 NRG \u5728\u5404\u79cd\u764c\u75c7\u7c7b\u578b\u4e2d\u7684\u4e2a\u4f53\u8868\u8fbe\u504f\u501a\uff0c\u5e76\u786e\u5b9a\u4e86 NET \u8bc4\u5206\u7684\u603b\u4f53\u9884\u540e\u5f71\u54cd\u3002\u672c\u7814\u7a76\u4f7f\u7528\u5355\u53d8\u91cf Cox \u6a21\u578b\u8ba1\u7b97\u4e86 NRG \u7684\u98ce\u9669\u6bd4 (HR)\uff0c\u5e76\u5c06 NRG \u7684\u5e73\u5747\u503c\u4f5c\u4e3a\u622a\u6b62\u503c\u3002\u672c\u7814\u7a76\u7ed8\u5236\u4e86 NRG \u7684 HR \u5206\u5e03\uff0c\u5e76\u5c06 NRG \u5206\u914d\u7ed9\u6cdb\u764c\u80cc\u666f\u4e0b\u9884\u540e\u4e0d\u826f\u6216\u826f\u597d\u7684\u9884\u540e\u6807\u5fd7\u7269\u7ec4\u3002\u7ed3\u679c\u53d1\u73b0NET \u76f8\u5173\u751f\u5b58\u7387\u8f83\u5dee\u7684\u764c\u75c7\u7c7b\u578b\u4e2d\u7684 NET \u76f8\u5173\u8c03\u63a7\u57fa\u56e0\u5f80\u5f80\u5177\u6709\u98ce\u9669\u51b3\u5b9a\u6027\uff0c\u4f8b\u5982 LGG \u548c GBM\uff08\u56fe 5A\u3001B\uff09\u3002\u5728 298 \u4e2a\u4e0e\u751f\u5b58\u7387\u4f4e\u7684\u764c\u75c7\u7c7b\u578b\u76f8\u5173\u7684 NRG \u4e2d\uff0c559 \u548c 562 \u4e2a\u6a21\u578b\u7b26\u5408 HR >1 \u6216 <1 \uff0c\u800c\u5728 122 \u4e2a\u5177\u6709\u826f\u597d\u751f\u5b58\u7387\u7684 NRG \u4e2d\uff0c\u5176\u4ed6\u6a21\u578b\u7b26\u5408 HR <1\uff08\u56fe 5C\uff09\u3002\u672c\u7814\u7a76\u9a8c\u8bc1\u4e86NET \u523a\u6fc0\u524d\u540e HepG2 \u7ec6\u80de\u8f6c\u5f55\u7ec4\u7684 RNAseq \u6570\u636e\u4e2d\u7684 NRG \u8868\u8fbe\u53d8\u5316\uff0c\u5e76\u4e14\u4e5f\u8bc1\u660e\u4e86\u8fd9\u4e9b\u57fa\u56e0\u5728 NET \u523a\u6fc0\u540e\u88ab\u4e0a\u8c03\uff08\u56fe 5D\uff09\u3002\u672c\u7814\u7a76\u5bf9 18 \u4e2a\u4e0e\u6cdb\u764c\u9884\u540e\u4e0d\u826f\u76f8\u5173\u7684 NRG\u300122 \u4e2a\u4e0e\u826f\u597d\u6cdb\u764c\u9884\u540e\u76f8\u5173\u7684 NRG \u548c 23 \u4e2a NET \u8bc4\u5206\u57fa\u56e0\u5e94\u7528\u4e86 STRING \u5206\u6790\uff08\u56fe 5E\uff09\u3002\u4ec5\u4fdd\u7559\u5177\u6709\u81f3\u5c11\u4e00\u79cd\u76f8\u4e92\u4f5c\u7528\u7684\u57fa\u56e0\uff0c\u5728 STRING \u6570\u636e\u5e93\u4e2d\u9274\u5b9a\u4e86\u603b\u5171 135 \u4e2a\u57fa\u56e0-\u57fa\u56e0\u76f8\u4e92\u4f5c\u7528\u3002NETs \u4e0e\u4e0e\u9884\u540e\u4e0d\u826f\u76f8\u5173\u7684 NRGs \u6709\u66f4\u5bc6\u5207\u7684\u5173\u8054\u3002<\/p>\n

\u56fe 5<\/p>\n

\u4e3a\u4e86\u8fdb\u4e00\u6b65\u63a2\u7d22\u8fd9\u4e9b\u57fa\u56e0\u7684\u751f\u7269\u5b66\u529f\u80fd\uff0c\u672c\u7814\u7a76\u8fdb\u884c\u4e86 KEGG \u6ce8\u91ca\u3002\u56fe\u4e2d\u663e\u793a\u4e86\u6309 p \u503c\u6392\u5e8f\u7684\u524d 10 \u6761\u5bcc\u96c6\u901a\u8def\uff08\u56fe 5F\u3001G\uff09\u3002\u5bf9\u4e8e\u4e0e\u6cdb\u764c\u9884\u540e\u4e0d\u826f\u76f8\u5173\u7684 NET \u76f8\u5173\u8c03\u63a7\u57fa\u56e0\uff0c\u4e0e\u7ec6\u80de\u5916\u57fa\u8d28\u8c03\u8282\u901a\u8def\u6700\u4e3a\u76f8\u5173\u3002\u5bf9\u4e8e\u4e0e\u6709\u5229\u7684\u6cdb\u764c\u9884\u540e\u76f8\u5173\u7684 NET \u76f8\u5173\u8c03\u8282\u57fa\u56e0\uff0cT \u7ec6\u80de\u514d\u75ab\u8c03\u8282\u5360\u4e3b\u5bfc\u5730\u4f4d\u300206SPP1\u4e3a\u4fc3\u8fdbNET\u76f8\u5173\u6076\u6027\u80bf\u7624\u7684\u5173\u952e\u57fa\u56e0<\/p>\n

\u672c\u7814\u7a76\u901a\u8fc7\u4ec5\u4fdd\u7559\u5728\u5177\u6709\u6709\u5229\/\u4e0d\u826f NET \u76f8\u5173\u751f\u5b58\u7684\u764c\u75c7\u7c7b\u578b\u7ec4\u4e2d\u5177\u6709\u6b63\u76f8\u5173\u6027 > 5 \u7684\u5bf9\u4ee5\u53ca\u5728\u53e6\u4e00\u7ec4\u764c\u75c7\u7c7b\u578b\u4e2d\u7684\u6b63\u76f8\u5173\u6027 < 2 \u6765\u7f29\u5c0f\u57fa\u56e0-NET \u5bf9\u7684\u6570\u91cf\u3002\u5728 NET \u76f8\u5173\u751f\u5b58\u7387\u826f\u597d\u6216\u8f83\u5dee\u7684\u764c\u75c7\u7c7b\u578b\u4e2d\uff0c\u672c\u7814\u7a76\u786e\u5b9a\u4e86 20 \u548c 11 \u4e2a Pearson R \u503c > 0.4 \u7684 NRG\uff08\u56fe 6A\uff09\u3002\u672c\u7814\u7a76\u6bd4\u8f83\u4e86\u4e24\u4e2a\u764c\u75c7\u7ec4\u4e4b\u95f4\u7684\u57fa\u56e0\u8868\u8fbe\u6c34\u5e73\uff0c\u5e76\u5b9a\u4e49\u4e86\u4e00\u7ec4\u4e0e NET \u666e\u904d\u76f8\u5173\u7684\u57fa\u56e0\uff0c\u5176\u4e2d SPP1 \u5728 NET \u76f8\u5173\u751f\u5b58\u7387\u8f83\u5dee\u7684\u764c\u75c7\u4e2d\u9ad8\u8868\u8fbe\uff08\u56fe 6B\uff09\u3002 SPP1 \u548c NET \u8bc4\u5206\u4e4b\u95f4\u7684 Pearson R \u503c\u8868\u660e\uff0cSPP1 \u4ec5\u5728 NET \u76f8\u5173\u751f\u5b58\u7387\u8f83\u5dee\u7684\u764c\u75c7\u7c7b\u578b\u4e2d\u4e0e NET \u8bc4\u5206\u5448\u6b63\u76f8\u5173\uff0c\u5728\u5177\u6709\u826f\u597d NET \u76f8\u5173\u751f\u5b58\u7387\u7684\u764c\u75c7\u7c7b\u578b\u4e2d\uff0c\u672a\u53d1\u73b0\u76f8\u5173\u6027\uff08\u56fe 6C\uff09\u3002\u672c\u7814\u7a76\u4f7f\u7528\u5355\u56e0\u7d20 Cox \u6a21\u578b\u8fdb\u4e00\u6b65\u63a2\u8ba8\u4e86\u57fa\u56e0\u548c NET \u8bc4\u5206\u5bf9\u60a3\u8005\u7ed3\u679c\u7684\u7efc\u5408\u5f71\u54cd\u3002\u7ed3\u679c\u53d1\u73b0\u4e0d\u540c\u4e9a\u7ec4\u4e4b\u95f4\u5b58\u5728\u663e\u8457\u7684\u751f\u5b58\u5dee\u5f02\uff0c\u5176\u4e2d SPP1\/NETs \u9ad8\u60a3\u8005\u4e2d\u9884\u540e\u8f83\u5dee\uff08\u56fe 6D\uff09\u3002\u672c\u7814\u7a76\u53d1\u73b0 SPP1 \u5728 NET \u76f8\u5173\u751f\u5b58\u7387\u8f83\u5dee\u7684\u764c\u75c7\u7c7b\u578b\u4e2d\u9ad8\u8868\u8fbe\u5e76\u4e0e NET \u8bc4\u5206\u76f8\u5173\u3002<\/p>\n<\/p>\n

\u56fe 6<\/p>\n

07SPP1\u4e0eNETs\u6f5c\u5728\u7684\u534f\u540c\u4fc3\u80bf\u7624\u4f5c\u7528<\/p>\n

\u57fa\u4e8e NET \u8bc4\u5206\u548c SPP1 \u8868\u8fbe\u6c34\u5e73\u4e4b\u95f4\u5bc6\u5207\u76f8\u5173\u7684\u4fc3\u80bf\u7624\u7f51\u7edc\u7684\u6570\u636e\u6316\u6398\uff0c\u672c\u7814\u7a76\u8fdb\u4e00\u6b65\u7814\u7a76\u4e86\u5b83\u4eec\u5bf9\u764c\u75c7\u884c\u4e3a\u53d1\u6325\u534f\u540c\u4f5c\u7528\u7684\u6f5c\u529b\u3002\u672c\u7814\u7a76\u6bd4\u8f83\u6bcf\u79cd\u764c\u75c7\u7c7b\u578b\u4e2dNETs\/ SPP1 \u9ad8\u7ec4\u548c\u4f4e\u7ec4\u7684EMT\u8bc4\u5206\u3002\u7ed3\u679c\u663e\u793a\u51e0\u4e4e\u6240\u6709\u764c\u75c7\u7c7b\u578b\u5728 NETs\/SPP1-high \u7ec4\u4e2d\u90fd\u663e\u793a\u51fa\u663e\u8457\u66f4\u9ad8\u7684 EMT \u5206\u6570\uff08\u56fe 7A\uff09\u3002<\/p>\n

\u5728\u8fdb\u4e00\u6b65\u7684\u5b9e\u9a8c\u9a8c\u8bc1\u4e2d\uff0c\u672c\u7814\u7a76\u901a\u8fc7 siRNA \u6572\u4f4e\u4e86 MHCC97H \u809d\u764c\u7ec6\u80de\u4e2d\u7684 SPP1 \u8868\u8fbe\uff08\u56fe 7B\u3001C\uff09\uff0c\u7136\u540e\u5e94\u7528NET\u523a\u6fc0\u3002\u5728\u809d\u764c\u4e2d\uff0cNETs\u5728Transwell\u8bd5\u9a8c\u4e2d\u4fc3\u8fdbMHCC97H\u7ec6\u80de\u7684\u4fb5\u88ad\uff1b\u7136\u800c\uff0cSPP1 \u6572\u4f4e\u6d88\u9664\u4e86 NET \u7684\u5165\u4fb5\u4fc3\u8fdb\u4f5c\u7528(\u56fe7D, E)\u3002\u5728\u4f53\u5916\u7cfb\u7edf\u4e2d\uff0c\u672c\u7814\u7a76\u63a2\u7d22\u4e86SPP1\u7f16\u7801\u86cb\u767dOPN\u5982\u4f55\u5f71\u54cd\u4e2d\u6027\u7c92\u7ec6\u80de\uff0c\u53d1\u73b0SPP1 (OPN)\u4fc3\u8fdb\u4e2d\u6027\u7c92\u7ec6\u80de\u8d8b\u5316\uff0cOPN\u76f4\u63a5\u523a\u6fc0NET\u7684\u5f62\u6210(\u56fe7F)\u3002SPP1\u7f16\u7801\u5206\u6ccc\u56e0\u5b50\u9aa8\u6865\u86cb\u767d(OPN)\uff0c\u5177\u6709\u5e7f\u6cdb\u7684\u514d\u75ab\u76f8\u5173\u8c03\u8282\u529f\u80fd\uff0c\u5c24\u5176\u662f\u9ad3\u7cfb\u7ec6\u80de\u3002<\/p>\n<\/p>\n

\u56fe 7<\/p>\n

\u7531\u4e8e\u672c\u7814\u7a76\u7684\u6570\u636e\u6316\u6398\u63ed\u793a\u4e86NET\u5f97\u5206\u4e0eSPP1\u8868\u8fbe\u4e4b\u95f4\u7684\u7d27\u5bc6\u8054\u7cfb\uff0c\u672c\u7814\u7a76\u5047\u8bbeSPP1\u4e5f\u53ef\u80fd\u5bf9NET\u5177\u6709\u8c03\u8282\u4f5c\u7528\u3002\u672c\u7814\u7a76\u5728\u5177\u6709 Hepa1-6 \u809d\u764c\u7ec6\u80de\u548c\u8fc7\u8868\u8fbe SPP1 (Hepa1-6spp1) \u7684 Hepa1-6 \u809d\u764c\u7ec6\u80de\u7684\u514d\u75ab\u6d3b\u6027\u5c0f\u9f20\u4e2d\u4f7f\u7528\u539f\u4f4d\u6a21\u578b\u3002\u7ed3\u679c\u53d1\u73b0\u643a\u5e26 Hepa1\u20136spp1 \u7684\u5c0f\u9f20\u5728\u809d\u810f\u80bf\u7624\u4e2d\u589e\u52a0\u4e86 NET \u5f62\u6210\uff0c\u5982\u4e24\u4e2a NET \u6807\u8bb0 MPO \u548c H3cit \u8868\u8fbe\u6240\u63ed\u793a\u7684\u90a3\u6837\uff08\u56fe 7G\u3001H\uff09\u3002\u8fd9\u4e9b\u7ed3\u679c\u8868\u660e SPP1 (OPN) \u548c NETs \u5728\u4fc3\u8fdb\u764c\u7ec6\u80de\u8f6c\u79fb\u65b9\u9762\u53ef\u80fd\u5b58\u5728\u5408\u4f5c\u3002<\/p>\n

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