■磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基α(PIK3CA)突变与肺癌的耐药性和预后有关;然而,组织样本和液体样本之间PIK3CA突变的一致性和临床价值尚不清楚.
■在2018年至2022年期间,在吉林省肿瘤医院收集了405例晚期肺癌患者的循环肿瘤DNA(ctDNA)和匹配的肿瘤组织样本,并使用基于520基因组的下一代测序对PIK3CA突变状态进行测序。MTT法检测不同突变肺癌细胞的活力。
■在810个肺癌样本中的46个(5.68%)中检测到PIK3CA突变,405个血浆样本中的21个(5.19%)和405个匹配组织中的25个(6.17%)。p.Glu542Lys,p.Glu545Lys,和p.His1047Arg是ctDNA和组织样本中最常见的PIK3CA突变类型。ctDNA与匹配组织间PIK3CA突变的一致性为97.53%(κ:0.770,P=0.000),敏感性/真阳性率为72.0%,特异性/真阴性率为99.2%,阴性预测值和阳性预测值分别为0.982和0.857(AUC=0.856,P=0.000)。此外,PIK3CA突变的一致性在肺腺癌中为98.26%,在肺鳞癌中为96.43%.TP53和EGFR是ctDNA和组织中最常见的伴随突变。具有PIK3CA突变的患者显示出较高的肿瘤突变负荷(TMB)(P<0.001),并且bTMB和tTMB之间存在显着相关性(r=0.5986,P=0.0041)。对于tPIK3CAmut/ctDNAPIK3CAmut队列,PI3K通路改变与男性相关(P=0.022),老年(P=0.007),和吸烟(P=0.001);tPIK3CAmut/ctDNAPIK3CAwt患者存在腺癌IV期的临床病理因素,PS评分低(≤1),TMB。
■这项研究表明,ctDNA对于识别PIK3CA突变是高度一致和敏感的,提示在液体样品中检测PIK3CA突变可能是组织的替代临床实践。
UNASSIGNED: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (
PIK3CA) mutations are associated with drug resistance and prognosis in lung cancer; however, the consistency and clinical value of PIK3CA mutations between tissue and liquid samples are unknown.
UNASSIGNED: Circulating tumor DNA (ctDNA) and matched tumor tissue samples from 405 advanced lung cancer patients were collected at Jilin Cancer Hospital between 2018 and 2022, and the
PIK3CA mutation status was sequenced using next-generation sequencing based on a 520 gene panel. The viability of different mutant lung cancer cells was detected using MTT assay.
UNASSIGNED: PIK3CA mutations were detected in 46 (5.68 %) of 810 lung cancer samples, with 21 (5.19 %) of 405 plasma samples and 25 (6.17 %) of 405 matched tissues. p.Glu542Lys, p.Glu545Lys, and p.His1047Arg were the most common mutation types of PIK3CA in both the ctDNA and tissue samples. The concordance of
PIK3CA mutations was 97.53 % between ctDNA and matched tissues (kappa: 0.770, P = 0.000), with sensitivity/true positive rate of 72.0 %, specificity/true negative rate of 99.2 %, and negative predictive value and positive predictive value of 0.982 and 0.857, respectively (AUC = 0.856, P = 0.000). Furthermore, the concordance of
PIK3CA mutations was 98.26 % in lung adenocarcinoma and 96.43 % in lung squamous cell carcinoma. TP53 and EGFR were the most common concomitant mutations in ctDNA and tissues. Patients with PIK3CA mutations showed a high tumor mutational burden (TMB) (P < 0.001) and a significant correlation between bTMB and tTMB (r = 0.5986, P = 0.0041). For the tPIK3CAmut/ctDNA PIK3CAmut cohort, PI3K pathways alteration was associated with male sex (P = 0.022), old age (P = 0.007), and smoking (P = 0.001); tPIK3CAmut/ctDNA PIK3CAwt patients harbored clinicopathological factors of adenocarcinoma stage IV, with low PS score (≤1) and TMB.
UNASSIGNED: This study showed that ctDNA is highly concordant and sensitive for identifying PIK3CA mutations, suggesting that PIK3CA mutation detection in liquid samples may be an alternative clinical practice for tissues.