Recent genome-wide association studies （GWAS） have identified a number of chromosomal regions associated with the risk of lung cancer. Of these regions, single-nucleotide polymorphisms （SNPs）, especially rs2736100...Recent genome-wide association studies （GWAS） have identified a number of chromosomal regions associated with the risk of lung cancer. Of these regions, single-nucleotide polymorphisms （SNPs）, especially rs2736100 located in the telomerase reverse transcriptase （TERT） gene show unique and significant association with non-small cell lung cancer （NSCLC） in a few subpopulations including women, nonsmokers, East Asians and those with adenocarcinoma, Recent studies have also linked rs2736100 with a longer telomere length and lung cancer risk. In this review, we seek to summarize the relationship between these factors and to further link the underlying telomere biology to lung cancer etiology. We conclude that genetic alleles combined with environmental （e.g., less-smoking） and physiological factors （gender and age） that confer longer telomere length are strong risk factors for NSCLC. This linkage may be particularly relevant in lung adenocarcinoma driven by epidermal growth factor receptor （EGFR） mutations, as these mutations have also been strongly linked to female gender, less-smoking history, adenocarcinoma histology and East Asian ethnicity, By establishing this connection, a strong argument is made for further investigating of the involvement of these entities during the tumorigenesis of NSCLC.展开更多
文摘目的研究肺腺癌中Ki-67表达与EGFR基因突变的相关性,并探索其在肺腺癌预后中的价值。方法回顾性分析2014年-2020年接受手术治疗的肺腺癌患者。采集患者临床病理信息、Ki-67表达与EGFR基因突变检测信息。采用卡方检验、Student’s t检验、方差分析等比较Ki-67表达、EGFR基因突变各组间差异;采用斯皮尔曼曼等级相关评价Ki-67蛋白表达与EGFR基因突变的相关性;采用Log-rank检验分析Ki-67表达及EGFR基因突变在肺腺癌预后中的价值。结果共纳入673例肺腺癌样本。Ki-67表达均数为21.37±20.43[中位数15(6~30)]。其中,462例发生EGFR突变,突变率为68.65%。Ki-67表达在男性、吸烟患者中更高,且与肿瘤大小、淋巴结转移正相关。EGFR基因突变发生率在女性、非吸烟患者中更高,并且与肿瘤大小、淋巴结转移负相关。发生EGFR突变患者,其Ki-67表达低于EGFR野生型患者(18.82±17.75 vs 26.97±24.45,P<0.001);一致地,Ki-67低表达(Ki-67<25)患者EGFR突变率高于Ki-67高表达(Ki-67≥25)患者(74.1%vs 57.0%,P<0.001)。斯皮尔曼曼等级相关分析显示,Ki-67表达与EGFR基因突变相关系数rho为-0.129(P<0.001)。生存分析结果表明,Ki-67高表达、EGFR野生型与较差的肺腺癌预后相关(P<0.05)。联合Ki-67表达与EGFR基因突变可见:与Ki-67表达≤10并且携带EGFR突变的患者相比,Ki-67>10并且EGFR野生型的患者预后更差,且HR值达4.46(95%CI:1.91~10.73,P<0.001)结论肺腺癌中,Ki-67表达与EGFR基因突变存在负相关关联,Ki-67表达与EGFR基因突变在肺腺癌预后中可能发挥联合作用。
基金supported in part by American Cancer SocietyIL Division (Grant No. 189273) (to W. Liu)Start-Up Fund of the College of Pharmacy, Purdue University (Grant No. 003055) (to W. Liu)
文摘Recent genome-wide association studies （GWAS） have identified a number of chromosomal regions associated with the risk of lung cancer. Of these regions, single-nucleotide polymorphisms （SNPs）, especially rs2736100 located in the telomerase reverse transcriptase （TERT） gene show unique and significant association with non-small cell lung cancer （NSCLC） in a few subpopulations including women, nonsmokers, East Asians and those with adenocarcinoma, Recent studies have also linked rs2736100 with a longer telomere length and lung cancer risk. In this review, we seek to summarize the relationship between these factors and to further link the underlying telomere biology to lung cancer etiology. We conclude that genetic alleles combined with environmental （e.g., less-smoking） and physiological factors （gender and age） that confer longer telomere length are strong risk factors for NSCLC. This linkage may be particularly relevant in lung adenocarcinoma driven by epidermal growth factor receptor （EGFR） mutations, as these mutations have also been strongly linked to female gender, less-smoking history, adenocarcinoma histology and East Asian ethnicity, By establishing this connection, a strong argument is made for further investigating of the involvement of these entities during the tumorigenesis of NSCLC.
文摘目的基于DA8600测序平台,探讨Ampli Seq建库方法检测EGFR基因突变所需最低样本DNA用量,以评估下一代测序(next generation sequencing,NGS)检测技术的性能。方法本研究选择10例EGFR突变的石蜡包埋组织样本,分别取1 ng、5 ng、10 ng、20 ng样本DNA进行文库构建,使用DA8600半导体测序仪进行检测,并比较检测结果。结果 10 ng和20 ng DNA用量均可全部准确检出EGFR基因突变;5 ng DNA用量准确检出7例EGFR基因突变,1例文库质量不合格无法进行测序,1例无法检出EGFR突变,1例测序数据量不足检测失败;1 ng DNA用量构建文库全部质量不合格,无法进行测序。结论通过对10例样本不同DNA用量构建文库的检测结果分析,说明10 ng DNA即可采用Ampli Seq建库方法在DA8600半导体测序仪进行EGFR基因突变检测。
