Potential utility of longitudinal somatic mutation and methylation profiling for predicting molecular residual disease in postoperative non‐small cell lung cancer patients
Abstract Growing efforts are being invested in investigating various molecular approaches to detect minimal residual disease (MRD) and predict disease recurrence. In our study, we investigated the utility of parallel longitudinal analysis of mutation and DNA methylation profiles for predicting MRD i...
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Wiley
2021
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oai:doaj.org-article:f9cf44dbf7b144dd826ad9e7c78bdd6b2021-12-01T04:49:15ZPotential utility of longitudinal somatic mutation and methylation profiling for predicting molecular residual disease in postoperative non‐small cell lung cancer patients2045-763410.1002/cam4.4339https://doaj.org/article/f9cf44dbf7b144dd826ad9e7c78bdd6b2021-12-01T00:00:00Zhttps://doi.org/10.1002/cam4.4339https://doaj.org/toc/2045-7634Abstract Growing efforts are being invested in investigating various molecular approaches to detect minimal residual disease (MRD) and predict disease recurrence. In our study, we investigated the utility of parallel longitudinal analysis of mutation and DNA methylation profiles for predicting MRD in postoperative non‐small‐cell lung cancer (NSCLC) patients. Tumor tissues and longitudinal blood samples were obtained from 65 patients with resected stage IA‐IIIB NSCLC. Somatic mutation and DNA methylation profiling were performed using ultra‐deep targeted sequencing and targeted bisulfite sequencing, respectively. Dynamic changes in plasma‐based mutation and tumor‐informed methylation profiles, reflected as MRD score, were observed from before surgery (baseline) to postoperative follow‐up, reflecting the decrease in tumor burden of the patients with resected NSCLC. Mutations were detected from plasma samples in 63% of the patients at baseline, which significantly reduced to 23‐25% during post‐operative follow‐ups. MRD score positive rate was 95.7% at baseline, which reduced to 74% at the first and 70% at the second follow‐up. Among the 5 relapsed patients with parallel longitudinal analysis of mutation and methylation profile, elevated MRD score was observed at follow‐up between 0.5‐7 months prior to radiologic recurrence for all 5 patients. Of them, 4 patients also had concomitant increase in allelic fraction of mutations in at least 1 follow‐up time point, but one patient had no mutation detected throughout all follow‐ups. Our results demonstrate that longitudinal profiling of mutation and DNA methylation may have potential for detecting MRD and predicting recurrence in postoperative NSCLC patients.Hang LiZe‐Lin MaBin LiYun‐jian PanJia‐Qing XiangYa‐Wei ZhangYi‐Hua SunTing HouAnalyn LizasoYan ChenXi LiHong HuWileyarticleDNA methylationmolecular residual diseaseprognostic biomarkerrecurrenceresected NSCLCNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancer Medicine, Vol 10, Iss 23, Pp 8377-8386 (2021) |
| institution |
DOAJ |
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DOAJ |
| language |
EN |
| topic |
DNA methylation molecular residual disease prognostic biomarker recurrence resected NSCLC Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
| spellingShingle |
DNA methylation molecular residual disease prognostic biomarker recurrence resected NSCLC Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Hang Li Ze‐Lin Ma Bin Li Yun‐jian Pan Jia‐Qing Xiang Ya‐Wei Zhang Yi‐Hua Sun Ting Hou Analyn Lizaso Yan Chen Xi Li Hong Hu Potential utility of longitudinal somatic mutation and methylation profiling for predicting molecular residual disease in postoperative non‐small cell lung cancer patients |
| description |
Abstract Growing efforts are being invested in investigating various molecular approaches to detect minimal residual disease (MRD) and predict disease recurrence. In our study, we investigated the utility of parallel longitudinal analysis of mutation and DNA methylation profiles for predicting MRD in postoperative non‐small‐cell lung cancer (NSCLC) patients. Tumor tissues and longitudinal blood samples were obtained from 65 patients with resected stage IA‐IIIB NSCLC. Somatic mutation and DNA methylation profiling were performed using ultra‐deep targeted sequencing and targeted bisulfite sequencing, respectively. Dynamic changes in plasma‐based mutation and tumor‐informed methylation profiles, reflected as MRD score, were observed from before surgery (baseline) to postoperative follow‐up, reflecting the decrease in tumor burden of the patients with resected NSCLC. Mutations were detected from plasma samples in 63% of the patients at baseline, which significantly reduced to 23‐25% during post‐operative follow‐ups. MRD score positive rate was 95.7% at baseline, which reduced to 74% at the first and 70% at the second follow‐up. Among the 5 relapsed patients with parallel longitudinal analysis of mutation and methylation profile, elevated MRD score was observed at follow‐up between 0.5‐7 months prior to radiologic recurrence for all 5 patients. Of them, 4 patients also had concomitant increase in allelic fraction of mutations in at least 1 follow‐up time point, but one patient had no mutation detected throughout all follow‐ups. Our results demonstrate that longitudinal profiling of mutation and DNA methylation may have potential for detecting MRD and predicting recurrence in postoperative NSCLC patients. |
| format |
article |
| author |
Hang Li Ze‐Lin Ma Bin Li Yun‐jian Pan Jia‐Qing Xiang Ya‐Wei Zhang Yi‐Hua Sun Ting Hou Analyn Lizaso Yan Chen Xi Li Hong Hu |
| author_facet |
Hang Li Ze‐Lin Ma Bin Li Yun‐jian Pan Jia‐Qing Xiang Ya‐Wei Zhang Yi‐Hua Sun Ting Hou Analyn Lizaso Yan Chen Xi Li Hong Hu |
| author_sort |
Hang Li |
| title |
Potential utility of longitudinal somatic mutation and methylation profiling for predicting molecular residual disease in postoperative non‐small cell lung cancer patients |
| title_short |
Potential utility of longitudinal somatic mutation and methylation profiling for predicting molecular residual disease in postoperative non‐small cell lung cancer patients |
| title_full |
Potential utility of longitudinal somatic mutation and methylation profiling for predicting molecular residual disease in postoperative non‐small cell lung cancer patients |
| title_fullStr |
Potential utility of longitudinal somatic mutation and methylation profiling for predicting molecular residual disease in postoperative non‐small cell lung cancer patients |
| title_full_unstemmed |
Potential utility of longitudinal somatic mutation and methylation profiling for predicting molecular residual disease in postoperative non‐small cell lung cancer patients |
| title_sort |
potential utility of longitudinal somatic mutation and methylation profiling for predicting molecular residual disease in postoperative non‐small cell lung cancer patients |
| publisher |
Wiley |
| publishDate |
2021 |
| url |
https://doaj.org/article/f9cf44dbf7b144dd826ad9e7c78bdd6b |
| work_keys_str_mv |
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1718405761691811840 |