Isobe Kazutoshi, Hata Yoshinobu, Tochigi Naobumi, Kaburaki Kyohei, Kobayashi Hiroshi, Makino Takashi, Otsuka Hajime, Ishida Fumiaki, Hirota Nao, Sano Go, Sugino Keishi, Sakamoto Susumu, Takai Yujiro, Shibuya Kazutoshi, Iyoda Akira, Homma Sakae
Division of Respiratory Medicine, Toho University School of Medicine, Tokyo, Japan.
Division Chest Surgery, Toho University School of Medicine, Tokyo, Japan.
Cancer Genomics Proteomics. 2015 Jan-Feb;12(1):31-7.
The present pilot study assessed the usefulness of nanofluidic digital polymerase chain reaction (PCR) arrays in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma after tyrosine kinase inhibitor (TKI) resistance.
We enrolled 12 patients with primary lung adenocarcinoma with sensitive EGFR mutation-confirmed T790M status by re-biopsy after TKI resistance. Nanofluidic digital PCR arrays were used to quantify T790M in genomic DNA from the pre-treatment primary site and in serum cell-free DNA (cfDNA).
On digital PCR, quantified T790M at the pre-treatment primary site was higher in re-biopsy-positive T790M patients (n=4) than in re-biopsy-negative patients (n=8) (0.78%±0.36% vs. 0.07%±0.09%, p<0.01). T790M at the pre-treatment primary site correlated with progression-free survival (PFS) after gefitinib therapy (r=0.67, p=0.016).
Use of digital PCR to quantify T790M at the primary site of EGFR-mutant lung adenocarcinoma predicted T790M emergence in re-biopsies after TKI resistance and PFS after gefitinib therapy.
本初步研究评估了纳米流体数字聚合酶链反应（PCR）阵列在酪氨酸激酶抑制剂（TKI）耐药后的表皮生长因子受体（EGFR）突变型肺腺癌中的应用价值。
我们纳入了12例原发性肺腺癌患者，这些患者在TKI耐药后通过再次活检确认了敏感的EGFR突变及T790M状态。使用纳米流体数字PCR阵列对预处理原发性部位的基因组DNA和血清游离DNA（cfDNA）中的T790M进行定量。
在数字PCR检测中，再次活检T790M阳性患者（n = 4）预处理原发性部位的T790M定量高于再次活检阴性患者（n = 8）（0.78%±0.36%对0.07%±0.09%，p<0.01）。预处理原发性部位的T790M与吉非替尼治疗后的无进展生存期（PFS）相关（r = 0.67，p = 0.016）。
使用数字PCR对EGFR突变型肺腺癌原发性部位的T790M进行定量，可预测TKI耐药后再次活检中T790M的出现及吉非替尼治疗后的PFS。
