目的:探究中国西南地区肺癌患者肿瘤易感基因胚系突变与体细胞突变特点及其临床病理特征。方法:回顾性分析重庆医科大学附属第一医院2019年1月至2022年12月收治的1198例肺癌患者的胚系基因测序数据,根据美国医学遗传学与基因组学学会遗...目的:探究中国西南地区肺癌患者肿瘤易感基因胚系突变与体细胞突变特点及其临床病理特征。方法:回顾性分析重庆医科大学附属第一医院2019年1月至2022年12月收治的1198例肺癌患者的胚系基因测序数据,根据美国医学遗传学与基因组学学会遗传突变分类标准指南、Clinvar数据库和Intervar数据库评估突变的致病性。比较携带基因致病性或可能致病性胚系突变(pathogenic/likely pathogenic, P/LP)患者与未携带基因致病性或可能致病性胚系突变患者的临床病理特征及体细胞突变特点。结果:1198例肺癌患者中,108例(9.02%)患者纳入P/LP+组,其中BRCA2基因突变10例,ATM基因突变8例,NOTCH3基因突变6例,FANCM基因突变5例,有56例患者伴发有EGFR体细胞突变,5例患者伴发有ALK体细胞突变;1090例(90.98%)患者纳入P/LP−组。与P/LP−组比较,P/LP+组患者临床分期多处于晚期(P 0.05)。P/LP+组与P/LP−组在体细胞突变上差异无统计学意义(P > 0.05)。结论:中国西南地区肺癌患者中致病性或可能致病性胚系突变发生率约为9%,携带有P/LP胚系突变的患者临床分期多为晚期,肺癌中P/LP胚系突变与驱动基因突变间未发现相关性。Objective: To examine the characteristics of germline and somatic mutations in tumor susceptibility genes among lung cancer patients in Southwest China, and to analyze their associations with clinicopathological features. Methods: This retrospective study analyzed germline gene sequencing data from 1198 lung cancer patients treated at The First Affiliated Hospital of Chongqing Medical University between January 2019 and December 2022. The pathogenicity of mutations was assessed according to the guidelines of the American College of Medical Genetics and Genomics (ACMG), as well as data from the Clinvar and Intervar databases. Clinicopathological characteristics and somatic mutation profiles were compared between patients with pathogenic or likely pathogenic germline mutations (P/LP group) and those without such mutations (non-P/LP group). Results: Of the 1198 lung cancer patients, 108 (9.02%) were classified into the P/LP+ group, with mutations identified in BRCA2 (10 cases), ATM (8 cases), NOTCH3 (6 cases), and FANCM (5 cases). Additionally, 56 patients in the P/LP+ group harbored concurrent EGFR somatic mutations, and 5 had concurrent ALK somatic mutations. The remaining 1090 patients (90.98%) were categorized into the non-P/LP− group. Compared with the non-P/LP− group, patients in the P/LP+ group were more likely to be diagnosed at an advanced clinical stage (P 0.05). Somatic mutation profiles did not differ significantly between the P/LP+ and non-P/LP− groups (P > 0.05). Conclusion: The prevalence of pathogenic or likely pathogenic germline mutations in lung cancer patients in Southwest China is approximately 9%. Patients with P/LP germline mutations are more likely to present at advanced stages. No significant correlation was observed between P/LP germline mutations and driver gene mutations in lung cancer.展开更多
肺结节是早期肺癌的一种表现,检出率逐年增高,早期诊断依赖于多种影像学,由于假阳性率高而无法精准评估,存在过度诊断。液体活检通过非侵入式方法对外周血中循环肿瘤细胞、DNA甲基化及非编码RNA进行检测,具有较高灵敏度和特异性,逐渐成...肺结节是早期肺癌的一种表现,检出率逐年增高,早期诊断依赖于多种影像学,由于假阳性率高而无法精准评估,存在过度诊断。液体活检通过非侵入式方法对外周血中循环肿瘤细胞、DNA甲基化及非编码RNA进行检测,具有较高灵敏度和特异性,逐渐成为肿瘤精准医疗领域强有力的诊断依据。本文就液体活检及其联合临床影像学在良恶性肺结节诊断中的研究进展进行综述。Pulmonary nodules are a manifestation of early-stage lung cancer, with detection rates increasing year by year. Early diagnosis relies on various imaging techniques, but the high rate of false positives makes it difficult to assess accurately, leading to overdiagnosis. Liquid biopsy, a non-invasive method, detects circulating tumor cells, DNA methylation, and non-coding RNA in peripheral blood with high sensitivity and specificity, gradually becoming a powerful diagnostic basis in the field of precision oncology. This article reviews the research progress of liquid biopsy and its combination with clinical imaging in the diagnosis of benign and malignant pulmonary nodules.展开更多
目的:研究红细胞(red blood cell,RBC)裂解液对CD34^+细胞相对计数的影响。方法:收集101份外周血干细胞采集物,CD34-PE及CD45-FITC双色免疫荧光染色后,分别用FACS裂解液(FACSTM lysing solution,FACS)、Optilyse C裂解液(optilyse C lys...目的:研究红细胞(red blood cell,RBC)裂解液对CD34^+细胞相对计数的影响。方法:收集101份外周血干细胞采集物,CD34-PE及CD45-FITC双色免疫荧光染色后,分别用FACS裂解液(FACSTM lysing solution,FACS)、Optilyse C裂解液(optilyse C lysing solution,Optilyse C)及自配裂解液溶解红细胞,采用洗涤程序和运用ISHAGE设门策略,检测CD34^+细胞、淋巴、粒、单核细胞相对数,CD45^+细胞占全部收集信号百分比及各类细胞前向散射光(forward scatter,FSC)及侧向散射光(side scatter,SSC)信号。结果:比较3种裂解液处理后样本的CD34^+细胞百分比,FACS裂解液处理的样本CD34^+细胞百分比最低,自配裂解液最高(FACS vs. Optilyse C vs.自配=0.49±0.43 vs. 0.67±0.50 vs. 0.73±0.66,P=0.000)。FACS裂解后样本CD45+细胞百分比远高于Optilyse C及自配裂解液(t=142.500,P=0.000)。3种裂解液对淋巴细胞百分比结果(F=35.340,P=0.000)具有统计学差异;而粒细胞百分比(F=0.610,P=0.540)、单核细胞百分比(F=1.590,P=0.210)差异无统计学意义。FACS裂解液处理后,CD34^+细胞、淋巴细胞的FSC和SSC信号强度均弱于Optilyse C裂解液及自配的裂解液;而粒、单核细胞的SSC信号,FACS裂解液处理后最强,Optilyse C裂解液处理后最弱。另外,动员后的白细胞数多少与CD34^+细胞百分比不存在相关性(r=0.108,P=0.312)。结论:红细胞裂解液导致CD34^+细胞相对计数差异的原因可能与CD45^+细胞比例有关,即获取的有效细胞数;裂解液对细胞形态的影响与造成淋巴细胞比例有显著性差异有关。鉴于不同红细胞裂解液对CD34等抗原阳性细胞的相对计数确实有不良影响,因此在应用流式细胞术检测或计数时应慎重选择。展开更多
文摘目的:探究中国西南地区肺癌患者肿瘤易感基因胚系突变与体细胞突变特点及其临床病理特征。方法:回顾性分析重庆医科大学附属第一医院2019年1月至2022年12月收治的1198例肺癌患者的胚系基因测序数据,根据美国医学遗传学与基因组学学会遗传突变分类标准指南、Clinvar数据库和Intervar数据库评估突变的致病性。比较携带基因致病性或可能致病性胚系突变(pathogenic/likely pathogenic, P/LP)患者与未携带基因致病性或可能致病性胚系突变患者的临床病理特征及体细胞突变特点。结果:1198例肺癌患者中,108例(9.02%)患者纳入P/LP+组,其中BRCA2基因突变10例,ATM基因突变8例,NOTCH3基因突变6例,FANCM基因突变5例,有56例患者伴发有EGFR体细胞突变,5例患者伴发有ALK体细胞突变;1090例(90.98%)患者纳入P/LP−组。与P/LP−组比较,P/LP+组患者临床分期多处于晚期(P 0.05)。P/LP+组与P/LP−组在体细胞突变上差异无统计学意义(P > 0.05)。结论:中国西南地区肺癌患者中致病性或可能致病性胚系突变发生率约为9%,携带有P/LP胚系突变的患者临床分期多为晚期,肺癌中P/LP胚系突变与驱动基因突变间未发现相关性。Objective: To examine the characteristics of germline and somatic mutations in tumor susceptibility genes among lung cancer patients in Southwest China, and to analyze their associations with clinicopathological features. Methods: This retrospective study analyzed germline gene sequencing data from 1198 lung cancer patients treated at The First Affiliated Hospital of Chongqing Medical University between January 2019 and December 2022. The pathogenicity of mutations was assessed according to the guidelines of the American College of Medical Genetics and Genomics (ACMG), as well as data from the Clinvar and Intervar databases. Clinicopathological characteristics and somatic mutation profiles were compared between patients with pathogenic or likely pathogenic germline mutations (P/LP group) and those without such mutations (non-P/LP group). Results: Of the 1198 lung cancer patients, 108 (9.02%) were classified into the P/LP+ group, with mutations identified in BRCA2 (10 cases), ATM (8 cases), NOTCH3 (6 cases), and FANCM (5 cases). Additionally, 56 patients in the P/LP+ group harbored concurrent EGFR somatic mutations, and 5 had concurrent ALK somatic mutations. The remaining 1090 patients (90.98%) were categorized into the non-P/LP− group. Compared with the non-P/LP− group, patients in the P/LP+ group were more likely to be diagnosed at an advanced clinical stage (P 0.05). Somatic mutation profiles did not differ significantly between the P/LP+ and non-P/LP− groups (P > 0.05). Conclusion: The prevalence of pathogenic or likely pathogenic germline mutations in lung cancer patients in Southwest China is approximately 9%. Patients with P/LP germline mutations are more likely to present at advanced stages. No significant correlation was observed between P/LP germline mutations and driver gene mutations in lung cancer.
文摘肺结节是早期肺癌的一种表现,检出率逐年增高,早期诊断依赖于多种影像学,由于假阳性率高而无法精准评估,存在过度诊断。液体活检通过非侵入式方法对外周血中循环肿瘤细胞、DNA甲基化及非编码RNA进行检测,具有较高灵敏度和特异性,逐渐成为肿瘤精准医疗领域强有力的诊断依据。本文就液体活检及其联合临床影像学在良恶性肺结节诊断中的研究进展进行综述。Pulmonary nodules are a manifestation of early-stage lung cancer, with detection rates increasing year by year. Early diagnosis relies on various imaging techniques, but the high rate of false positives makes it difficult to assess accurately, leading to overdiagnosis. Liquid biopsy, a non-invasive method, detects circulating tumor cells, DNA methylation, and non-coding RNA in peripheral blood with high sensitivity and specificity, gradually becoming a powerful diagnostic basis in the field of precision oncology. This article reviews the research progress of liquid biopsy and its combination with clinical imaging in the diagnosis of benign and malignant pulmonary nodules.
文摘目的:研究红细胞(red blood cell,RBC)裂解液对CD34^+细胞相对计数的影响。方法:收集101份外周血干细胞采集物,CD34-PE及CD45-FITC双色免疫荧光染色后,分别用FACS裂解液(FACSTM lysing solution,FACS)、Optilyse C裂解液(optilyse C lysing solution,Optilyse C)及自配裂解液溶解红细胞,采用洗涤程序和运用ISHAGE设门策略,检测CD34^+细胞、淋巴、粒、单核细胞相对数,CD45^+细胞占全部收集信号百分比及各类细胞前向散射光(forward scatter,FSC)及侧向散射光(side scatter,SSC)信号。结果:比较3种裂解液处理后样本的CD34^+细胞百分比,FACS裂解液处理的样本CD34^+细胞百分比最低,自配裂解液最高(FACS vs. Optilyse C vs.自配=0.49±0.43 vs. 0.67±0.50 vs. 0.73±0.66,P=0.000)。FACS裂解后样本CD45+细胞百分比远高于Optilyse C及自配裂解液(t=142.500,P=0.000)。3种裂解液对淋巴细胞百分比结果(F=35.340,P=0.000)具有统计学差异;而粒细胞百分比(F=0.610,P=0.540)、单核细胞百分比(F=1.590,P=0.210)差异无统计学意义。FACS裂解液处理后,CD34^+细胞、淋巴细胞的FSC和SSC信号强度均弱于Optilyse C裂解液及自配的裂解液;而粒、单核细胞的SSC信号,FACS裂解液处理后最强,Optilyse C裂解液处理后最弱。另外,动员后的白细胞数多少与CD34^+细胞百分比不存在相关性(r=0.108,P=0.312)。结论:红细胞裂解液导致CD34^+细胞相对计数差异的原因可能与CD45^+细胞比例有关,即获取的有效细胞数;裂解液对细胞形态的影响与造成淋巴细胞比例有显著性差异有关。鉴于不同红细胞裂解液对CD34等抗原阳性细胞的相对计数确实有不良影响,因此在应用流式细胞术检测或计数时应慎重选择。
