Undetectable circulating tumor DNA levels correlate with low risk of recurrence/metastasis in postoperative pathologic stage I lung adenocarcinoma patients
| Autor: | Yang W. Shao, Xiaoyu Hong, Man Yu, X. Fu, Weixiong Yang, Sai Ching J. Yeung, Zhenguo Liu, Zengding Lao, Yinguang Wang, Bo Zeng, Wei Ou, Qiuxiang Ou, Minghan Jia, Na You, Xue Wu, Siyu Wang, Chao Cheng, Zhanfei Zhang, Jiali Yang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Oncology Cancer Research medicine.medical_specialty Lung Neoplasms Adenocarcinoma of Lung Ground-glass opacity Metastasis Circulating Tumor DNA Epigenesis Genetic 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Biomarkers Tumor Humans Lung Proportional hazards model business.industry Cancer medicine.disease Confidence interval 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cohort Adenocarcinoma medicine.symptom Neoplasm Recurrence Local business |
| Zdroj: | Lung cancer (Amsterdam, Netherlands). 146 |
| ISSN: | 1872-8332 |
| Popis: | The application of circulating tumor DNA (ctDNA) monitoring after resection in pathologic(p) stage I lung adenocarcinoma (LUAD) patients remains controversial and it is of great clinical interest to decipher the difference of genetic features between ground-glass opacity (GGO) and solid nodules (non-GGO) subgroups. We aim to assess the utility of ctDNA in tracking early recurrence or metastasis following surgery and reveal the genetic differences between GGO and non-GGO.Tumor tissues and matched postoperative plasma samples were collected from a total of 82 (p)stage I LUAD patients. Comprehensive genomic profiling was performed using capture-based hybrid next generation sequencing by targeting 422 cancer relevant genes.EGFR and TP53 represent commonly mutated genes in this cohort of (p)stage I lung adenocarcinoma, followed by alterations in ALK, PIK3CA, STK11 and MYC. For a median follow-up period of 22.83 months after surgery, 65 out of 67 ctDNA-negative patients remained progression-free, while 3 out of 15 ctDNA-positive patients progressed [P = 0.040; positive predictive value = 0.20, 95 % confidence interval (CI), 0.04-0.48; negative predictive value = 0.97, 95 % CI, 0.9-1]. With time-dependent Cox regression analysis, we observed that ctDNA positivity significantly correlated with increased probability of early tumor recurrence or metastasis (P = 0.02, HR=8.5). Further comparison between GGO and non-GGO subgroups indicated the frequency of TP53 mutations in non-GGO was markedly higher than that in GGO (47 % vs 21 %, P 0.05). Pathway analysis showed the epigenetic regulation pathway was more frequently affected in GGO subgroup, while impaired apoptosis/cell cycle pathway was more enriched in non-GGO LUADs.Our longitudinal ctDNA monitoring data showed that undetectable ctDNA may predict low risk of tumor recurrence or metastasis in postoperative (p)stage I LUAD patients, while it requires further investigation on how robust the positive ctDNA results could predict tumor relapse in these patients.NCT03172156. |
| Databáze: | OpenAIRE |
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