Liquid biopsy for early stage lung cancer

Liang, Wenhua; Zhao, Yi; Huang, Weiguo; Liang, Hengrui; Zeng, Haikang; He, Jianxing

doi:10.21037/jtd.2018.04.26

Cited by 35 publications

(36 citation statements)

References 85 publications

(48 reference statements)

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“…Therefore, being able to escape from destruction by immune cells is necessary for cancer cells to successfully metastasize, which has been experimentally demonstrated in animal studies [ 54 , 55 ]. Cancer cell shedding into blood is not uncommon, even for early stage diseases [ 56 ], though not all patients with circulating tumor cells develop metastases. Therefore, it is possible that only the cells capable of escaping immune surveillance could survive and form distant metastases.…”

Section: Discussionmentioning

confidence: 99%

Multiomics profiling of primary lung cancers and distant metastases reveals immunosuppression as a common characteristic of tumor cells with metastatic plasticity

Lee

Reuben

et al. 2020

Genome Biol

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Background Metastasis is the primary cause of cancer mortality accounting for 90% of cancer deaths. Our understanding of the molecular mechanisms driving metastasis is rudimentary. Results We perform whole exome sequencing (WES), RNA sequencing, methylation microarray, and immunohistochemistry (IHC) on 8 pairs of non-small cell lung cancer (NSCLC) primary tumors and matched distant metastases. Furthermore, we analyze published WES data from 35 primary NSCLC and metastasis pairs, and transcriptomic data from 4 autopsy cases with metastatic NSCLC and one metastatic lung cancer mouse model. The majority of somatic mutations are shared between primary tumors and paired distant metastases although mutational signatures suggest different mutagenesis processes in play before and after metastatic spread. Subclonal analysis reveals evidence of monoclonal seeding in 41 of 42 patients. Pathway analysis of transcriptomic data reveals that downregulated pathways in metastases are mainly immune-related. Further deconvolution analysis reveals significantly lower infiltration of various immune cell types in metastases with the exception of CD4+ T cells and M2 macrophages. These results are in line with lower densities of immune cells and higher CD4/CD8 ratios in metastases shown by IHC. Analysis of transcriptomic data from autopsy cases and animal models confirms that immunosuppression is also present in extracranial metastases. Significantly higher somatic copy number aberration and allelic imbalance burdens are identified in metastases. Conclusions Metastasis is a molecularly late event, and immunosuppression driven by different molecular events, including somatic copy number aberration, may be a common characteristic of tumors with metastatic plasticity.

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Section: Discussionmentioning

confidence: 99%

Multiomics profiling of primary lung cancers and distant metastases reveals immunosuppression as a common characteristic of tumor cells with metastatic plasticity

Lee

Reuben

et al. 2020

Genome Biol

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“…Although tissue biopsy is the gold standard for molecular genotyping in lung cancer, liquid biopsy may play an important role as a complementary method for targeted gene detection and the prediction of the clinical course or outcome [15,16], as well as for the detection of lung cancer at an early stage [17]. Liquid biopsy is a relatively non-invasive, safe, and simple procedure.…”

Section: Discussionmentioning

confidence: 99%

Compared to plasma, bronchial washing fluid shows higher diagnostic yields for detecting EGFR-TKI sensitizing mutations by ddPCR in lung cancer

Lee¹,

Kim²,

Kim³

et al. 2020

Respir Res

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Background: The rate of diagnosis of advanced lung adenocarcinoma must be improved. In this study, we compared the detection rates of EGFR-tyrosine kinase inhibitor-sensitizing mutations (mEGFRs) in bronchial washing fluid (BWF) and the plasma of patients with lung adenocarcinoma using the tissue genotype as the standard reference. Methods: Paired blood and BWF specimens were collected from 73 patients with lung cancer. The tumor EGFR mutation status was determined by genotyping of the plasma and BWF samples using droplet digital PCR (ddPCR). Results: The study cohort included 26, 10, 10, and 27 patients with stage I, II, III, and IV disease. Of the 73 cases, 35 had a wild-type EGFR, and 19 had the L858R substitution and exon 19 deletion mutations. The areas under the receiver operator characteristic curves for sensitivity vs. specificity of ddPCR were 0.895 [95% confidence interval (CI): 0.822-0.969] for BWF and 0.686 (95% CI: 0.592-0.780) for plasma (p < 0.001). The fractional abundance was higher in BWF of the mEGFR-positive cases than in the plasma (p = 0.004), facilitating easy threshold setting and discrimination between mEGFR-positive and negative cases. When genotyping results obtained using plasma and BWF were compared for early lung cancer (stages I-IIIA), the diagnostic yields were significantly higher for BWF ddPCR, and the same tendency was observed for the advanced stages, suggesting that the BWF data may reflect the genotype status in early-stage patients. Conclusions: The mEGFR genotyping results obtained using BWF showed a higher diagnostic efficacy than did those obtained using the plasma. Thus, BWF-based genotyping may be a useful substitute for that using plasma in lung cancer.

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“…From previous surgical series, a detectable plasma EGFR ctDNA after radical surgery suggested the presence of molecular/minimal residual disease (MRD). In these series, the persistence of plasma ctDNA identified patients at high risk of relapse and preceded radiological progression by a median of 70 days to 5.2 months [7,8,10,19,20]. This association between post-treatment ctDNA and MRD may apply to radiotherapy patients as well [8,11] and may be useful to complement follow-up radiological scans for diagnosis of relapse.…”

Section: Discussionmentioning

confidence: 84%

“…The protocol was later amended to allow for use of multi gene panel (gene list: ALK, BRAF, ERBB2, EGFR [exons [18][19][20][21], KRAS, MET, NRAS, PIK3CA, STK11, and TP53) NGS LiquidMARK TM test [12] on the stored frozen plasma samples.…”

Section: Plasma Egfr Mutation Ctdna Proceduresmentioning

confidence: 99%

Baseline Plasma EGFR Circulating Tumour DNA Levels in a Pilot Cohort of EGFR-Mutant Limited-Stage Lung Adenocarcinoma Patients Undergoing Radical Lung Radiotherapy

et al. 2020

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The use of circulating cell-free tumour DNA (ctDNA) is established in metastatic lung adenocarcinoma to detect and monitor sensitising EGFR mutations. In early-stage disease, there is very little data supporting its role as a potential biomarker. We report on a prospective cohort of 9 limited-stage EGFR mutant lung cancer patients who were treated with radical radiotherapy. We looked at baseline plasma EGFR ctDNA and noted the detection rates to be higher in locally advanced disease. At a median follow-up of 13.5 months, an association between a detectable pre-radiotherapy plasma EGFR ctDNA and early tumour relapse (155 days vs. NR, p = 0.004) was noted. One patient with persistent plasma EGFR ctDNA predated radiological progression. The role of ctDNA in early-stage lung cancer is developing. Plasma EGFR ctDNA could be a useful biomarker in lung cancer patients undergoing radical treatments for staging, prognostication, and follow-up. These preliminary findings should be explored in larger studies.

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Liquid biopsy for early stage lung cancer

Cited by 35 publications

References 85 publications

Multiomics profiling of primary lung cancers and distant metastases reveals immunosuppression as a common characteristic of tumor cells with metastatic plasticity

Multiomics profiling of primary lung cancers and distant metastases reveals immunosuppression as a common characteristic of tumor cells with metastatic plasticity

Compared to plasma, bronchial washing fluid shows higher diagnostic yields for detecting EGFR-TKI sensitizing mutations by ddPCR in lung cancer

Baseline Plasma EGFR Circulating Tumour DNA Levels in a Pilot Cohort of EGFR-Mutant Limited-Stage Lung Adenocarcinoma Patients Undergoing Radical Lung Radiotherapy

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