González de Aledo-Castillo José Manuel, Serhir-Sgheiri Samira, Calbet-Llopart Neus, Arcocha Ainara, Jares Pedro, Reguart Noemí, Puig-Butillé Joan Antón
Biochemistry and Molecular Genetics Department, Hospital Clínic, 08036 Barcelona, Spain.
Molecular Biology CORE, Hospital Clínic, 08036 Barcelona, Spain.
Diagnostics (Basel). 2021 Jul 22;11(8):1319. doi: 10.3390/diagnostics11081319.
The cobas EGFR Test provides a semiquantitative index (SQI) that reflects the proportion of mutated versus wild-type copies of the gene in plasma. The significance of SQI as an indirect measure of the variant allele frequency (VAF) or mutated copies/mL remains unclear. The aim of this study was to evaluate the correlation of SQI with the VAF and the number of mutated copies/mL obtained by a digital droplet PCR (ddPCR) test in NSCLC samples. The study included 118 plasma samples from a retrospective cohort of 25 stage IV adenocarcinoma patients with exon 19 deletions (Ex19Del), obtained before and during tyrosine kinase inhibitor (TKI) treatment. Both SQI and VAF and SQI and mutated copies/mL showed the same significant correlation (r = 0.79, < 0.00001) across the whole study cohort. We found better correlation in samples collected at the baseline between SQI and VAF (r = 0.94, < 0.00001) and SQI and mutated copies/mL (r = 0.97, < 0.00001) compared to samples collected during TKI treatment: r = 0.76; < 0.00001 for SQI and VAF and r = 0.75; < 0.00001 for SQI and mutated copies/mL. The study indicates that SQI is a robust quantitative indirect measure of VAF and the number of mutated copies/mL in plasma from patients with an Ex19Del mutation. Further studies are desirable to assess the SQI cut-off values related to the clinical status of the patient.
cobas EGFR检测可提供一个半定量指标(SQI),该指标反映了血浆中该基因的突变型与野生型拷贝数的比例。SQI作为变异等位基因频率(VAF)或每毫升突变拷贝数的间接测量指标,其意义尚不清楚。本研究的目的是评估非小细胞肺癌(NSCLC)样本中SQI与VAF以及通过数字液滴PCR(ddPCR)检测获得的每毫升突变拷贝数之间的相关性。该研究纳入了118份血浆样本,这些样本来自25例IV期腺癌且伴有外显子19缺失(Ex19Del)患者的回顾性队列,样本采集于酪氨酸激酶抑制剂(TKI)治疗前及治疗期间。在整个研究队列中,SQI与VAF以及SQI与每毫升突变拷贝数均呈现相同的显著相关性(r = 0.79,P < 0.00001)。我们发现,与TKI治疗期间采集的样本相比,基线时采集的样本中,SQI与VAF(r = 0.94,P < 0.00001)以及SQI与每毫升突变拷贝数(r = 0.97,P < 0.00001)之间的相关性更好:SQI与VAF的r = 0.76,P < 0.00001;SQI与每毫升突变拷贝数的r = 0.75,P < 0.00001。该研究表明,SQI是Ex19Del突变患者血浆中VAF和每毫升突变拷贝数的可靠定量间接测量指标。需要进一步研究以评估与患者临床状态相关的SQI临界值。