For decades,the central dogma of oncology has been that a cancer’s identity is inextricably linked to its anatomical origin.This principle underpins the entire diagnostic and therapeutic framework,from histology-base...For decades,the central dogma of oncology has been that a cancer’s identity is inextricably linked to its anatomical origin.This principle underpins the entire diagnostic and therapeutic framework,from histology-based classification to site-specific treatment guidelines.Yet,this framework catastrophically fails for a substantial population of patients diagnosed with cancer of unknown primary(CUP).These patients present metastatic disease,yet their primary tumors remain elusive despite exhaustive clinical workup1.CUP,accounting for 1%-3%of all cancer diagnoses,is an enigma with devastating consequences;the median overall survival is only 2-12 months2-4.The inability to pinpoint an origin forces clinicians to rely on broad-spectrum empirical chemotherapy,such as taxane-carboplatin regimens,which have limited efficacy and exclude patients from the promise of targeted therapies and clinical trials5.CUP is not only a diagnostic challenge but also an indictment of the siloed approach to understanding malignancy:this cancer highlights the limitations of origin-based diagnostic frameworks.However,the confluence of high-dimensional biological data and advanced artificial intelligence(AI)is now poised to address this long-standing diagnostic limitation and to herald a new era for not only CUP but also oncology as a whole(Figure 1).展开更多
目的分析沉默分化簇(CD)147对非小细胞肺癌(NSCLC)细胞生物学特征及上皮间质转化(EMT)的影响,并探究可能的相关分子机制。方法回顾性收集2023年8月~2024年3月空军军医大学唐都医院收治的30例NSCLC患者癌灶组织及癌旁正常组织样本,从中...目的分析沉默分化簇(CD)147对非小细胞肺癌(NSCLC)细胞生物学特征及上皮间质转化(EMT)的影响,并探究可能的相关分子机制。方法回顾性收集2023年8月~2024年3月空军军医大学唐都医院收治的30例NSCLC患者癌灶组织及癌旁正常组织样本,从中科院细胞库购买人正常肺上皮细胞BEAS-2B及NSCLC细胞系A549、NCI-H460、NCI-H1299,采用实时荧光定量PCR(qRT-PCR)法检测NSCLC癌灶组织和癌旁正常组织,以及各细胞系中CD147 mRNA表达水平。将NCI-H460细胞分为control组、si-NC组、si-CD147组、SC-79组及si-CD147+SC-79组,通过CCK-8法、Transwell法及流式细胞仪检测敲低CD147对NSCLC细胞增殖、迁移、凋亡的影响。蛋白免疫印迹(Western blot)检测EMT相关标志物神经钙黏蛋白(N-cadherin)、波形蛋白(Vimentin)、上皮钙黏附蛋白(E-cadherin)及锌指转录因子(Slug)、扭曲蛋白(Twist)表达,以及磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(AKT)/哺乳动物雷帕霉素靶蛋白(mTOR)通路相关蛋白表达。结果NSCLC组织中CD147 mRNA(1.64±0.25)表达水平明显高于癌旁正常组织(0.43±0.06),差异具有统计学意义(t=8.152,P<0.05)。NSCLC细胞中CD147 mRNA表达水平较人正常肺上皮细胞明显升高(1.24±0.13、3.31±0.37、2.16±0.29 vs 0.35±0.04),差异具有统计学意义(F=80.516,P<0.05)。与control组相比,si-CD147组细胞增殖率(53.74%±4.07%vs 78.92%±6.23%)、迁移率(19.57%±2.69%vs 37.24%±3.12%)明显降低,细胞凋亡率(39.04%±2.74%vs 16.14%±2.14%)明显升高(t=5.548、7.068、12.036),N-cadherin(0.41±0.02 vs 1.01±0.02)、Vimentin(0.36±0.04 vs 1.02±0.04)蛋白表达降低,E-cadherin(1.85±0.14 vs 0.98±0.02)蛋白表达升高,Slug(0.49±0.03 vs 1.02±0.03)和Twist(0.53±0.05 vs 1.03±0.04)蛋白水平明显抑制(t=12.766~36.742),p-PI3K(0.42±0.03 vs 1.01±0.03)、p-AKT(0.45±0.03 vs 1.01±0.02)和p-mTOR(0.38±0.02 vs 0.99±0.02)蛋白表达水平明显降低(t=8.377、7.286、9.694),差异具有统计学意义(均P<0.05)。与SC-79组相比,si-CD147+SC-79组p-PI3K、p-AKT、p-mTOR蛋白表达明显升高(t=11.075、14.573、13.666),促进细胞增殖及迁移、降低细胞凋亡、促进EMT过程(t=2.834~11.396),差异具有统计学意义(均P<0.05);SC-79可逆转敲低CD147对PI3K/AKT/mTOR通路的影响(t=11.643、8.848、10.965)和PI3K/AKT/mTOR通路相关蛋白的表达(t=2.595~14.476),差异具有统计学意义(均P<0.05)。结论CD147高表达可通过PI3K/AKT/mTOR通路诱导EMT过程,促进肿瘤细胞的增殖及迁移,抑制细胞凋亡,参与NSCLC的发生发展。展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.32270688,31801117,and 82430107 to X.L.,and 32500589 to H.S.)the China Postdoctoral Science Foundation(Grant Nos.BX20240253 and 2024M762384 to H.S.)+1 种基金the Natural Science Foundation of Tianjin(Grant No.24JCQNJC01280 to H.S.)Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-3-003A).
文摘For decades,the central dogma of oncology has been that a cancer’s identity is inextricably linked to its anatomical origin.This principle underpins the entire diagnostic and therapeutic framework,from histology-based classification to site-specific treatment guidelines.Yet,this framework catastrophically fails for a substantial population of patients diagnosed with cancer of unknown primary(CUP).These patients present metastatic disease,yet their primary tumors remain elusive despite exhaustive clinical workup1.CUP,accounting for 1%-3%of all cancer diagnoses,is an enigma with devastating consequences;the median overall survival is only 2-12 months2-4.The inability to pinpoint an origin forces clinicians to rely on broad-spectrum empirical chemotherapy,such as taxane-carboplatin regimens,which have limited efficacy and exclude patients from the promise of targeted therapies and clinical trials5.CUP is not only a diagnostic challenge but also an indictment of the siloed approach to understanding malignancy:this cancer highlights the limitations of origin-based diagnostic frameworks.However,the confluence of high-dimensional biological data and advanced artificial intelligence(AI)is now poised to address this long-standing diagnostic limitation and to herald a new era for not only CUP but also oncology as a whole(Figure 1).
文摘目的 探讨双期相双能量CT(dual-energy computed tomography,DECT)灌注成像在肺癌患者术前肺功能评估中的应用价值。方法 收集2022年11月—2024年6月于南京医科大学第一附属医院胸外科行手术治疗的ⅠA期非小细胞肺癌患者,术前均进行DECT灌注成像和肺功能检查(pulmonary function testing,PFT)。PFT观察指标包括通气功能指标如第一秒用力呼气量(forced expiratory volume in one second,FEV1)、用力肺活量(forced vital capacity,FVC)、1秒率(FEV1/FVC)、最大通气量(maximal voluntary ventilation,MVV),和弥散功能指标如一氧化碳弥散量(diffusing capacity for carbon monoxide,DLCO)、比弥散量(DLCO per liter of alveolar volume,DLCO/VA)。采用软件eXamine获得DECT灌注成像的定量参数,包括两肺及各肺叶的容积参数和灌注参数。分析两肺容积参数、灌注参数与患者的通气功能、弥散功能指标的相关性,以及各肺叶定量参数的差别。结果 吸气末相肺容积和双相容积差与FEV1、FVC呈强正相关(r=0.636,r=0.682,r=0.614,r=0.624,P<0.001),与MVV、DLCO呈中等程度正相关(r=0.499,r=0.514,r=0.549,r=0.447,P<0.001);呼气末相肺容积与DLCO/VA呈弱负相关(r=-0.295,P=0.026);容积比与FEV1、FVC、MVV、MVV占预测值百分比(MVV%)呈正相关(r=0.424,r=0.399,r=0.415,r=0.310,P<0.05);吸气末相碘含量与DLCO/VA占预测值百分比(DLCO/VA%)呈弱正相关(rs=0.292,P=0.030);呼气末相碘含量与FEV1、FVC、MVV、DLCO占预测值百分比(DLCO%)、DLCO/VA呈弱正相关(r=0.307,r=0.299,r=0.295,r=0.366,r=0.320,P<0.05),与DLCO呈中等程度正相关(r=0.439,P<0.001);吸气末相碘浓度与FEV1、FVC、MVV、MVV%呈负相关(rs=-0.407,rs=-0.426,rs=-0.352,rs=-0.277,P<0.05);呼气末相碘浓度与DLCO/VA呈中等程度正相关(r=0.403,P=0.002);碘浓度差和碘浓度比均与FEV1、FEV1占预测值百分比(FEV1%)、FVC、MVV、MVV%呈中等程度正相关(P<0.05)。肺容积、碘浓度比值均以左肺上叶最大,右肺中叶最小;肺容积差、肺容积比、肺内碘含量及肺内碘浓度差均以两肺下叶最高,右肺中叶最小。结论 双期相DECT灌注成像检查可以准确评估患者整体肺功能并量化区域肺功能。
文摘目的分析沉默分化簇(CD)147对非小细胞肺癌(NSCLC)细胞生物学特征及上皮间质转化(EMT)的影响,并探究可能的相关分子机制。方法回顾性收集2023年8月~2024年3月空军军医大学唐都医院收治的30例NSCLC患者癌灶组织及癌旁正常组织样本,从中科院细胞库购买人正常肺上皮细胞BEAS-2B及NSCLC细胞系A549、NCI-H460、NCI-H1299,采用实时荧光定量PCR(qRT-PCR)法检测NSCLC癌灶组织和癌旁正常组织,以及各细胞系中CD147 mRNA表达水平。将NCI-H460细胞分为control组、si-NC组、si-CD147组、SC-79组及si-CD147+SC-79组,通过CCK-8法、Transwell法及流式细胞仪检测敲低CD147对NSCLC细胞增殖、迁移、凋亡的影响。蛋白免疫印迹(Western blot)检测EMT相关标志物神经钙黏蛋白(N-cadherin)、波形蛋白(Vimentin)、上皮钙黏附蛋白(E-cadherin)及锌指转录因子(Slug)、扭曲蛋白(Twist)表达,以及磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(AKT)/哺乳动物雷帕霉素靶蛋白(mTOR)通路相关蛋白表达。结果NSCLC组织中CD147 mRNA(1.64±0.25)表达水平明显高于癌旁正常组织(0.43±0.06),差异具有统计学意义(t=8.152,P<0.05)。NSCLC细胞中CD147 mRNA表达水平较人正常肺上皮细胞明显升高(1.24±0.13、3.31±0.37、2.16±0.29 vs 0.35±0.04),差异具有统计学意义(F=80.516,P<0.05)。与control组相比,si-CD147组细胞增殖率(53.74%±4.07%vs 78.92%±6.23%)、迁移率(19.57%±2.69%vs 37.24%±3.12%)明显降低,细胞凋亡率(39.04%±2.74%vs 16.14%±2.14%)明显升高(t=5.548、7.068、12.036),N-cadherin(0.41±0.02 vs 1.01±0.02)、Vimentin(0.36±0.04 vs 1.02±0.04)蛋白表达降低,E-cadherin(1.85±0.14 vs 0.98±0.02)蛋白表达升高,Slug(0.49±0.03 vs 1.02±0.03)和Twist(0.53±0.05 vs 1.03±0.04)蛋白水平明显抑制(t=12.766~36.742),p-PI3K(0.42±0.03 vs 1.01±0.03)、p-AKT(0.45±0.03 vs 1.01±0.02)和p-mTOR(0.38±0.02 vs 0.99±0.02)蛋白表达水平明显降低(t=8.377、7.286、9.694),差异具有统计学意义(均P<0.05)。与SC-79组相比,si-CD147+SC-79组p-PI3K、p-AKT、p-mTOR蛋白表达明显升高(t=11.075、14.573、13.666),促进细胞增殖及迁移、降低细胞凋亡、促进EMT过程(t=2.834~11.396),差异具有统计学意义(均P<0.05);SC-79可逆转敲低CD147对PI3K/AKT/mTOR通路的影响(t=11.643、8.848、10.965)和PI3K/AKT/mTOR通路相关蛋白的表达(t=2.595~14.476),差异具有统计学意义(均P<0.05)。结论CD147高表达可通过PI3K/AKT/mTOR通路诱导EMT过程,促进肿瘤细胞的增殖及迁移,抑制细胞凋亡,参与NSCLC的发生发展。
