Evaluation of liquid biopsies for molecular profiling and monitoring in non-small cell lung cancer (NSCLC) patients.

V-Raf murine sarcoma viral oncogene homolog B (BRAF) gene mutations have recently been approved to select advanced stages non-small cell lung cancer (NSCLC) patients for tyrosine kinase inhibitors treatments. In this setting, liquid biopsy may represent a valuable option for BRAF mutational testing in patients without tissue availability. Here, we reviewed 196 plasma based liquid biopsies analysed by an in-house developed next generation sequencing panel, termed SiRe. On the overall, 6 (3.1%) out of 196 BRAF mutated cases were identified, with an overall median allelic frequency of 3.4%. Exon 15 p.V600E was the most common detected mutation (2/6, 33.3%). Our data highlighted that the SiRe panel is a robust tool for BRAF mutation assessment on circulating tumour DNA. Further investigation is required to develop a diagnostic algorithm to harmonise BRAF testing on tissue and blood in advanced stages NSCLC patients.

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Molecular profiling of response to platinum based therapy in non-small cell lung cancer (NSCLC) patients

Journal of Clinical Oncology ◽

10.1200/jco.2004.22.14_suppl.2104 ◽

2004 ◽

Vol 22 (14_suppl) ◽

pp. 2104-2104

Author(s):

R. D. Petty ◽

G. I. Murray ◽

K. Kerr ◽

M. C. Nicolson ◽

D. Bissett ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Molecular Profiling ◽

Small Cell ◽

Small Cell Lung ◽

Nsclc Patients

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Biomarkers France: a first and distinctive step in assessing the impact of non-small cell lung cancer (NSCLC) patients routine molecular profiling

Translational Cancer Research ◽

10.21037/tcr.2016.09.24 ◽

2016 ◽

Vol 5 (S3) ◽

pp. S608-S609

Author(s):

Fabrice Barlesi ◽

Jean-Charles Soria ◽

Dominique Maraninchi ◽

Norbert Ifrah ◽

Denis Moro-Sibilot

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Molecular Profiling ◽

Small Cell ◽

Small Cell Lung ◽

Nsclc Patients ◽

The Impact

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The Analysis of Platelet-Derived circRNA Repertoire as Potential Diagnostic Biomarker for Non-Small Cell Lung Cancer

Cancers ◽

10.3390/cancers13184644 ◽

2021 ◽

Vol 13 (18) ◽

pp. 4644

Author(s):

Silvia D’Ambrosi ◽

Allerdien Visser ◽

Mafalda Antunes-Ferreira ◽

Ankie Poutsma ◽

Stavros Giannoukakos ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Blood Platelets ◽

Small Cell ◽

Rna Seq ◽

Small Cell Lung ◽

Liquid Biopsies ◽

Asymptomatic Individuals ◽

Nsclc Patients

Tumor-educated Platelets (TEPs) have emerged as rich biosources of cancer-related RNA profiles in liquid biopsies applicable for cancer detection. Although human blood platelets have been found to be enriched in circular RNA (circRNA), no studies have investigated the potential of circRNA as platelet-derived biomarkers for cancer. In this proof-of-concept study, we examine whether the circRNA signature of blood platelets can be used as a liquid biopsy biomarker for the detection of non-small cell lung cancer (NSCLC). We analyzed the total RNA, extracted from the platelet samples collected from NSCLC patients and asymptomatic individuals, using RNA sequencing (RNA-Seq). Identification and quantification of known and novel circRNAs were performed using the accurate CircRNA finder suite (ACFS), followed by the differential transcript expression analysis using a modified version of our thromboSeq software. Out of 4732 detected circRNAs, we identified 411 circRNAs that are significantly (p-value < 0.05) differentially expressed between asymptomatic individuals and NSCLC patients. Using the false discovery rate (FDR) of 0.05 as cutoff, we selected the nuclear receptor-interacting protein 1 (NRIP1) circRNA (circNRIP1) as a potential biomarker candidate for further validation by reverse transcription–quantitative PCR (RT-qPCR). This analysis was performed on an independent cohort of platelet samples. The RT-qPCR results confirmed the RNA-Seq data analysis, with significant downregulation of circNRIP1 in platelets derived from NSCLC patients. Our findings suggest that circRNAs found in blood platelets may hold diagnostic biomarkers potential for the detection of NSCLC using liquid biopsies.

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Liquid biopsy: Safety and efficacy in a tool for molecular profiling of advanced non-small cell lung cancer (NSCLC).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21506 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21506-e21506

Author(s):

Saleha Rizwan ◽

Zachary Otaibi ◽

Herman Lo ◽

Talal Khan ◽

Rodney E. Wegner ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Targeted Therapies ◽

Liquid Biopsy ◽

Small Cell ◽

Molecular Testing ◽

Small Cell Lung ◽

Liquid Biopsies ◽

Nsclc Patients

e21506 Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with a broad spectrum of targeted therapies already available or in clinical trials. Among the NSCLC patients, 23% to 25% harbor a mutation in a gene associated with approved or emerging targeted therapy. These therapies have changed the therapeutic landscape of NSCLC with significantly improved clinical outcomes in advanced metastatic NSCLC patients. It is imperative to test for these gene alterations in order to identify patients who could potentially benefit from these efficacious targeted therapies and to avoid therapies unlikely to provide clinical benefit. A major limitation in obtaining molecular testing occurs when minimally invasive techniques are used to obtain tissue sample resulting in insufficient yield for testing. In such cases, the utilization of circulating tumor DNA (ctDNA), commonly known as liquid biopsy, has proven very beneficial. In a study utilizing ctDNA, increased detection rates were found when using ctDNA in addition to tissue testing and a > 98.2% concordance rate was found. We report results of 40 NSCLC patients from our institute who had liquid biopsy with or without tissue profiling done. Methods: We molecularly profiled 40 newly diagnosed advanced NSCLC patients using both tissue and liquid biopsies. Tissue was assayed using the John Hopkins university molecular panel and liquid biopsies were performed by Biocept. Results: 14 out of 40 (35%) patients had insufficient or no tissue for molecular testing. Concordant results were found in 17 out of the 26 (65.4%) patients who had both tissue and liquid molecular testing done. Liquid Biopsy detected additional mutations in 5 (19.2%) patients which were not picked up on tissue and led to change in management in 4 patients. 12 out of 40 (30%) patients had repeat liquid biopsies done at progression of disease with new mutations detected on 4 patients revealing resistance to current treatment and change in treatment. Conclusions: Liquid Biopsy reveals high concordance rates with tissue genotyping and increases rate of detection of targetable mutations in NSCLC. It offers a safe and effective alternative when additional tissue is needed to identify genetic mutations.

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