Liquid biopsy in early stage lung cancer

Pérez-Ramírez, Cristina; Cañadas-Garre, Marisa; Robles, Ana I.; Molina, Miguel Ángel; Faus-Dáder, María José; Calleja‐Hernández, Miguel Ángel

doi:10.21037/tlcr.2016.10.15

Cited by 32 publications

(23 citation statements)

References 56 publications

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“…Although some studies have found no correlation between ctDNA levels and tumor burden, 24,27 most studies have suggested that detection of ctDNA is significantly associated with tumor burden. [28][29][30][31] In this study, bone metastasis was associated with detectable ctDNA, supporting the higher detection rate of ctDNA in patients with a more extensive tumor burden.…”

Section: Discussionsupporting

confidence: 76%

Correlation between progression‐free survival, tumor burden, and circulating tumor DNA in the initial diagnosis of advanced‐stage EGFR‐mutated non‐small cell lung cancer

et al. 2018

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BackgroundThis study was conducted to identify whether the presence of circulating tumor DNA (ctDNA) in plasma before treatment with EGFR‐tyrosine kinase inhibitors (TKIs) is associated with clinical outcomes.MethodsFifty‐seven pairs of tissues and plasma samples were obtained from patients with NSCLC adenocarcinoma harboring activating EGFR mutations before the administration of EGFR‐TKI treatment. ctDNA mutation was identified using the PANAMutyper EGFR mutation kit. Both qualitative and quantitative analyzes of the data were performed.ResultsConcordance rates with tissue biopsy were 40.4% and 59.6% for the qualitative and quantitative methods, respectively. Bone metastasis showed a statistically significant correlation with ctDNA detection (odds ratio 3.985, 95% confidence interval [CI] 1.027–15.457; P = 0.046). Progression‐free survival (PFS) was significantly shorter in the group detected with ctDNA than in the undetected ctDNA group (median PFS 9.8 vs. 20.7 months; hazard ratio [HR] 2.30, 95% CI 1.202–4.385; P = 0.012). Detection of ctDNA before treatment with EGFR‐TKIs (HR 2.388, 95% CI 1.138–5.014; P = 0.021) and extra‐thoracic lymph node metastasis (HR 13.533, 95% CI 2.474–68.747; P = 0.002) were independently associated with PFS. Six of 11 patients (45.5%) monitored by serial sampling showed a dynamic change in ctDNA prior to disease progression.ConclusionQuantitative testing can increase the sensitivity of the ctDNA detection test. Patients with detectable ctDNA had significantly shorter PFS after receiving EGFR‐TKIs than those with undetectable ctDNA. Tumor burden may be associated with plasma ctDNA detection. A shorter PFS was associated with detection of ctDNA and extra‐thoracic lymph node metastasis. Dynamic changes in the ctDNA level may help predict clinical outcomes.

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Section: Discussionsupporting

confidence: 76%

Correlation between progression‐free survival, tumor burden, and circulating tumor DNA in the initial diagnosis of advanced‐stage EGFR‐mutated non‐small cell lung cancer

et al. 2018

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“…Lung cancer is the most common cause global cancer mortality, 39 and TP53 mutated lung cancer displays an increased mutational burden, increased expression of immune checkpoint proteins, increased T cell infiltration, and PD-L1 amplification and derives remarkable clinical benefit from PD-1 inhibitors. 21 However, the mechanisms by which TP53 mutation affects the microenvironment and lung cancer prognosis.…”

Section: Discussionmentioning

confidence: 99%

A TP53 -associated gene signature for prediction of prognosis and therapeutic responses in lung squamous cell carcinoma

Lin

et al. 2020

OncoImmunology

106

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The tumor-suppressor gene tumor protein p53 (TP53) is one of the most commonly mutated genes in human lung cancer, and TP53 mutations are associated with a worsened prognosis and causes resistance to cancer therapy. RNA sequencing and TP53 mutation data were downloaded to determine specific TP53associated signature based on differentially expressed genes between patients with lung squamous cell carcinoma (LUSC) with wild type (TP53 WT) and mutated (TP53 MUT) TP53. We investigated the predictive value of this signature on the immune microenvironment, tumor mutational burden (TMB), and likelihood of response to immunotherapy and chemotherapy. In total, 1,556 differentially expressed genes were identified based on TP53 mutation status. Three genes (KLK6, MUC22 and CSN1S1) identified by univariate and multivariate Cox regression analyses, comprised the prognostic signature which was an independent and specific prognostic marker of overall survival in patients with LUSC. A nomogram was also established to validate this signature for clinical use. Moreover, the high-risk group was characterized by increased infiltration of monocytes and macrophages M1, and decreased T cells CD8 and T cells follicular helper. Highrisk group exhibited a higher TMB, and was much more sensitive to immunotherapy and chemotherapy. KLK6 and CSN1S1 expression and the prognostic prediction values were further validated in clinical samples. The derived TP53-associated signature is a specific and independent prognostic biomarker for LUSC patients, and could provide potential prognostic biomarker or therapeutic targets for the development of novel immunotherapies and chemotherapies.

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“…Circulating miRNAs have been recently used as biological markers for early diagnosis, prognosis, prediction of response to therapy and clinical outcome, particularly in a liquid biopsy setting [1][2][3][4][5][6][7][8][9][10][11][77][78][79] . Liquid biopsy is a powerful tool applicable to all or most human cancers, including colorectal, lung, melanoma, and breast neoplasms [80,81] . From a more general viewpoint, tumor-xenotransplanted mice and other in vivo models may have an important role because they resolve biological variables from technical variables (such as handling and storage of biological fluids, pre-analytical processing, as well as DNA and RNA isolation protocols) that might affect efficient marker detection by liquid biopsy [82,83] .…”

Section: Resultsmentioning

confidence: 99%

Circulating microRNAs and liquid biopsy: murine xenograft models for technical validation of clinical protocols

Gasparello¹,

Allegretti²,

Papi³

et al. 2019

JCMT

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In oncology, liquid biopsy is applied to detect with high efficiency clinically relevant analytes, such as tumor cells, cell-free nucleic acids, and exosomes in peripheral blood and other body fluids of cancer patients. Liquid biopsy is considered one of the most advanced non-invasive diagnostic systems useful, in the next future, for enabling personalized treatments in precision medicine. Medical actions include, but are not limited to, early diagnosis, staging, prognosis, anticipation (lead time) and prediction of therapy responses, as well as follow up. Experimental system for validation of the proposed liquid biopsy approaches is highly needed. In this review article we will discuss the establishment of xenotransplanted mouse model systems for the validation of liquid biopsy protocols aimed to identify changes in the miRNA plasma content. Human colon cancer HT-29 and LoVo cells have been xenotransplanted and miR-221-3p and miR-222-3p have been comparatively analyzed in cultured HT-29 and LoVo cells, xenotransplants and plasma samples.

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Liquid biopsy in early stage lung cancer

Cited by 32 publications

References 56 publications

Correlation between progression‐free survival, tumor burden, and circulating tumor DNA in the initial diagnosis of advanced‐stage EGFR‐mutated non‐small cell lung cancer

Correlation between progression‐free survival, tumor burden, and circulating tumor DNA in the initial diagnosis of advanced‐stage EGFR‐mutated non‐small cell lung cancer

A TP53 -associated gene signature for prediction of prognosis and therapeutic responses in lung squamous cell carcinoma

Circulating microRNAs and liquid biopsy: murine xenograft models for technical validation of clinical protocols

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