Spatiotemporal genomic analysis reveals distinct molecular features in recurrent stage I non-small cell lung cancers

Yang, Aixia; Carbone, David P.; Kanu, Nnennaya; Liu, Ke; Wang, Ruiru; Nie, Yuntao; Shen, Haifeng; Bai, Jian; Wu, Lin; Li, Hui; Shi, Yanchao; Mok, Tony; Yu, Jun; Yang, Fan; Wu, Shuangxiu; Jamal‐Hanjani, Mariam; Wang, Jun

doi:10.1016/j.celrep.2022.111047

Cited by 7 publications

(15 citation statements)

References 54 publications

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“…According to our findings, patients without any mutation in both blood components had a significantly better median RFS compared to patients who had at least one detectable mutation. The same finding was revealed for the detection of mutations in plasma-cfDNA, which is in agreement with the findings of Chen et al [ 16 ], who performed deep 457 gene-targeted NGS on 55 plasma cfDNAs of stage I NSCLC patients and reported a significant association between cfDNA detection and decreased DFS ( p = 0.02) [ 16 ]. Additionally, based on the findings of Walcken et al [ 40 ], ctDNA detection soon after tumor resection identifies patients at risk for relapse.…”

Section: Discussionsupporting

confidence: 90%

“…Τhe mutational landscape of CTCs in NSCLC patients may provide novel tumor biomarkers for early diagnosis of lung cancer [ 14 ] and reflect the emergence of clonal evolution under selective treatment pressure [ 15 ]. Very recently, it has been shown that recurrent tumors have distinct somatic alteration events compared with recurrent-free tumors and could demonstrate a variety of alterations correlated with time to recurrence [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Preoperative Mutational Analysis of Circulating Tumor Cells (CTCs) and Plasma-cfDNA Provides Complementary Information for Early Prediction of Relapse: A Pilot Study in Early-Stage Non-Small Cell Lung Cancer

Markou

Londra

Stergiopoulou

et al. 2023

Cancers

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Purpose: We assessed whether preoperativemutational analyses of circulating tumor cells (CTCs) and plasma-cfDNA could be used as minimally invasive biomarkers and as complimentary tools for early prediction of relapse in early-stage non-small -cell lung cancer (NSCLC). Experimental Design: Using ddPCR assays, hotspot mutations of BRAF, KRAS, EGFR and PIK3CA were identified in plasma-cfDNA samples and size-based enriched CTCs isolated from the same blood samples of 49 early-stage NSCLC patients before surgery and in a control group of healthy blood donors (n = 22). Direct concordance of the mutational spectrum was further evaluated in 27 patient-matched plasma-cfDNA and CTC-derived DNA in comparison to tissue-derived DNA. Results: The prevalence of detectable mutations of the four tested genes was higher in CTC-derived DNA than in the corresponding plasma-cfDNA (38.8% and 24.5%, respectively).The most commonly mutated gene was PIK3CA, in both CTCs and plasma-cfDNA at baseline and at the time of relapse. Direct comparison of the mutation status of selected drug-responsive genes in CTC-derived DNA, corresponding plasma-cfDNA and paired primary FFPE tissues clearly showed the impact of heterogeneity both within a sample type, as well as between different sample components. The incidence of relapse was higher when at least one mutation was detected in CTC-derived DNA or plasma-cfDNA compared with patients in whom no mutation was detected (p = 0.023). Univariate analysis showed a significantly higher risk of progression (HR: 2.716; 95% CI, 1.030–7.165; p = 0.043) in patients with detectable mutations in plasma-cfDNA compared with patients with undetectable mutations, whereas the hazard ratio was higher when at least one mutation was detected in CTC-derived DNA or plasma-cfDNA (HR: 3.375; 95% CI, 1.098–10.375; p = 0.034). Conclusions: Simultaneous mutational analyses of plasma-cfDNA and CTC-derived DNA provided complementary molecular information from the same blood sample and greater diversity in genomic information for cancer treatment and prognosis. The detection of specific mutations in ctDNA and CTCs in patients with early-stage NSCLC before surgery was independently associated with disease recurrence, which represents an important stratification factor for future trials.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Preoperative Mutational Analysis of Circulating Tumor Cells (CTCs) and Plasma-cfDNA Provides Complementary Information for Early Prediction of Relapse: A Pilot Study in Early-Stage Non-Small Cell Lung Cancer

Markou

Londra

Stergiopoulou

et al. 2023

Cancers

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“…Thus, we conducted further investigations to address these confusions. Simulated data reveals the optimal panels and clonal relatedness interpretation WES data of the 235 samples from 80 patients with solitary non-small cell lung cancer (NSCLC) in our institution (22) were used for MLCs simulation and subsampling of different panels. To corroborate the rationality that paired samples from the same tumor mimic IPM while samples from distinct patients represent MPLC, we reviewed the mutational landscape of the solitary NSCLC cohort (Figure 3A).…”

Section: Resultsmentioning

confidence: 99%

Optimizing the NGS-based discrimination of multiple lung cancers from the perspective of evolution

Wang,

Yuan,

Liu

et al. 2024

Preprint

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Background: Next-generation sequencing (NGS) can help differentiate multiple primary lung cancers (MPLC) from intrapulmonary metastasis (IPM), but remains vague in panel choice and clonal relatedness interpretation. Methods: First, cases with definite diagnosis of MPLC or IPM were simulatedusing the whole-exome sequencing (WES)data from 80 single lung cancer, samples from different tumors mimicking MPLC while those from the same tumor simulating IPM. Different panels were modeled by gene subsampling. Two interpretation methods of clonal relatedness were compared: counting the shared mutations (MoleA) versus probability calculation based on all the mutations (MoleB). We drew ROC curves for each panel and interpretation method with reference to the definite diagnosis, and selected the optimal combinations according to area under the ROC curve (AUCs) and inconclusive rate. Results: MoleB outperformed MoleA with all panels. The AUCs plateaued at high levels when applying NCCNplus MoleB (9 driver genes recommended by the National Comprehensive Cancer Network [NCCN] plus TP53) (AUC = 0.950±0.002) or pancancer MoleA (363-genes) (AUC = 0.792±0.004). Then the superiority of selected strategies was validated in two independent cohorts of multiple lung cancers. All NGS-based methodologies significantly separated the disease-free survival in the WES cohort (N = 42), and NCCNplus MoleB also successfully stratified the prognosis in the non-WES cohort (N = 94). Further phylogenetic analysis and timing of driver alterations revealed the evolutionary differences between MPLC and IPM. Conclusions: These findings have established the first modified panel and corresponding NGS-based procedures to discriminate multiple lung cancers (MLCs).

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“…Among the 11 prospective observational studies selected for the present meta-analysis, 4 studies (Provencio et al 2022 ; Gale et al 2022 ; Tan et al 2021 ; Waldeck et al 2022 ) were conducted with the European population and 7 studies (Xia et al 2022 ; Peng et al 2020 ; Qiu et al 2021 ; Li et al 2022 ; Zhang et al 2022 ; Yue et al 2022 ; Chen et al 2022 ) were conducted with the Asian population. Irrespective of the pathological types of NSCLC, LUAD accounted for a significant proportion (73%) in the study population, while lung squamous carcinoma (LUSC) accounted for just 20%.…”

Section: Resultsmentioning

confidence: 99%

“…Irrespective of the pathological types of NSCLC, LUAD accounted for a significant proportion (73%) in the study population, while lung squamous carcinoma (LUSC) accounted for just 20%. In regard to NSCLC staging, Provencio et al ( 2022 ) focused only on stage III NSCLC patients, Chen et al ( 2022 ) limited their evaluation to patients with stage I NSCLC, and the remaining nine studies (Gale et al 2022 ; Xia et al 2022 ; Tan et al 2021 ; Waldeck et al 2022 ; Peng et al 2020 ; Qiu et al 2021 ; Li et al 2022 ; Zhang et al 2022 ; Yue et al 2022 ) included patients with stage I–III NSCLC. In addition to surgery, neoadjuvant therapy (NAT) was stated in the full text of three studies (Provencio et al 2022 ; Zhang et al 2022 ; Yue et al 2022 ), among which the study of Zhang et al ( 2022 ) was excluded due to a lack of detailed data.…”

Section: Resultsmentioning

confidence: 99%

Prognostic value of preoperative circulating tumor DNA in non-small cell lung cancer: a systematic review and meta-analysis

Lu,

Feng,

Guo

et al. 2024

J Cancer Res Clin Oncol

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Background Several recent studies have reported the increasing application of preoperative circulating tumor DNA (ctDNA) as a biomarker of tumor burden for guiding potential postoperative treatment strategies. Methods A meta-analysis of prospective/retrospective cohort studies was conducted to compare the prognosis of preoperatively genetically positive and genetically negative NSCLC patients. The endpoints used in the included studies were overall survival (OS) and recurrence-free survival (RFS). The objective of the meta-analysis was to comprehensively explore the prognostic value of preoperative ctDNA for patients with non-small-cell lung cancer (NSCLC) and its significance in guiding postoperative adjuvant therapy (AT) in patients with NSCLC. Results The preliminary analysis identified 1565 studies, among which only 11 studies fulfilled the eligibility criteria and were finally included in the present systematic review and meta-analysis. The statistical results revealed that the expression of preoperative ctDNA was associated with worse RFS (HR = 3.00; 95% CI 2.26–3.98; I2 = 0%) and OS (HR = 2.77; 95% CI 1.67–4.58; I2 = 0%), particularly in lung adenocarcinoma (LUAD) patients (RFS: HR = 3.46; 95% CI 2.37–5.05; I2 = 0%; OS: HR = 3.52; 95% CI 1.91–6.49; I2 = 0%) and patients with I–II stage of NSCLC (RFS: HR = 2.84; 95% CI 1.88–4.29; I2 = 0%; OS: HR = 2.60; 95% CI 1.43–4.74; I2 = 0%). Moreover, compared to patients with negative preoperative ctDNA, patients with positive preoperative ctDNA presented greater survival benefits (HR = 0.39; 95% CI 0.22–0.67; I2 = 2%) from postoperative AT. Conclusion The evaluation of the prognostic value of preoperative ctDNA revealed that preoperative ctDNA might be used as a prognostic biomarker for patients with LUAD or those with stage I–II NSCLC. In addition, postoperative AT is recommended for NSCLC patients with positive preoperative ctDNA, regardless of the disease stage and subtype.

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Spatiotemporal genomic analysis reveals distinct molecular features in recurrent stage I non-small cell lung cancers

Cited by 7 publications

References 54 publications

Preoperative Mutational Analysis of Circulating Tumor Cells (CTCs) and Plasma-cfDNA Provides Complementary Information for Early Prediction of Relapse: A Pilot Study in Early-Stage Non-Small Cell Lung Cancer

Preoperative Mutational Analysis of Circulating Tumor Cells (CTCs) and Plasma-cfDNA Provides Complementary Information for Early Prediction of Relapse: A Pilot Study in Early-Stage Non-Small Cell Lung Cancer

Optimizing the NGS-based discrimination of multiple lung cancers from the perspective of evolution

Prognostic value of preoperative circulating tumor DNA in non-small cell lung cancer: a systematic review and meta-analysis

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