Rescue of Non-Informative Circulating Tumor DNA to Monitor the Mutational Landscape in NSCLC

Mayer, Stefanie; Schmidtke-Schrezenmeier, Gerlinde; Buske, Christian; Rücker, Frank G.; Barth, Thomas F.E.; Møller, Peter L.; Marienfeld, Ralf

doi:10.3390/cancers12071917

“…The range has been reported to be between 10 and 1000 ng/µL in some studies [17], while others have shown it to be between 0.1 and 12 ng/µL. Similarly, the ctDNA concentration in healthy donors has also varied in past studies, ranging from 0 to 100 ng/µL [18]. It is important to note that comparing results from different studies can be challenging due to differences in sample size, patient populations, and detection methods.…”

Section: Discussionmentioning

confidence: 99%

Circulating-tumour DNA methylation of HAND1 gene: a promising biomarker in early detection of colorectal cancer

Shavali,

Moradi,

Tahmaseb

et al. 2024

BMC Med Genomics

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Background Colorectal cancer (CRC) is one of the significant global health concerns with an increase in cases. Regular screening tests are crucial for early detection as it is often asymptomatic in the initial stages. Liquid biopsies, a non-invasive approach that examines biomarkers in biofluids, offer a promising future in diagnosing and screening cancer. Circulating-tumour DNA (ctDNA) is the genetic material in biofluids released into the circulatory system by cells. ctDNA is a promising marker for monitoring patients since cancer cells display distinct DNA methylation patterns compared to normal cells. The potential of our research to contribute to early detection and improved patient outcomes is significant. Aims The primary objective of this research project was to explore the HAND1 methylation levels in plasma ctDNA as a potential biomarker for diagnosing CRC and evaluate the methylation level of the well-established gene SPET9 to compare it with the methylation level of HAND1. Materials and methods Plasma samples were collected from 30 CRC patients and 15 healthy individuals, with CRC samples obtained pre-treatment. ctDNA was extracted and treated with bisulfite for methylation status assessment. Quantitative methylation-specific PCR (qMS-PCR) was performed for HAND1 and SEPT9, using β-actin (ACTB gene) as a reference. The study aims to evaluate the potential of these genes as diagnostic biomarkers for CRC, contributing to early detection and improved patient outcomes. Results Our study yielded significant results: 90% of CRC patients (27 out of 30) had hypermethylation in the SEPT9 gene, and 83% (25 out of 30) exhibited hypermethylation in the HAND1 gene. The methylation levels of both genes were significantly higher in CRC patients than in healthy donors. These findings underscore the potential of SEPT9 and HAND1 methylation as promising biomarkers for diagnosing CRC, potentially leading to early detection and improved patient outcomes. Conclusion These findings highlight the potential of SEPT9 and HAND1 methylation as promising biomarkers for diagnosing CRC. However, further research and validation studies are needed to confirm these findings and to explore their clinical utility in CRC diagnosis and management.

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“…The complexity of the testing process requires sophisticated laboratory equipment, highly trained medical personnel, and prolonged processing time (days, even weeks). These limitations have led to skepticism regarding the clinical utility of this technology 64 .…”

Section: Ultra-sensitive Sensor and Multiplex Analysis For Dynamic Ch...mentioning

confidence: 99%

A New Approach Towards Non-Invasive Cancer Diagnostics – Discerning Cancer Stem Cell Signatures in Blood with Self-Functionalized Quantum Sensor Probes

Haldavnekar

2024

Preprint

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This dissertation describes the development of liquid biopsy using the signals of cancer stem cells (CSCs) in blood as a standalone diagnostic modality. Considering the complexity of cancer, it is necessary to capture the tumour-heterogeneity for robust diagnosis. Current state of the art with non-invasive methods relying on imaging has many limitations such as low sensitivity, inability to identify recurrent tumor or discrimination between primary or metastatic tumors. Since imaging-based diagnosis fails to provide sufficient specificity, tissue biopsyremainstobe thegoldstandardfordefinitive diagnosis. However, tissuebiopsyishighlyinvasive and can only provide a snapshot of the tumor, failing to capture the dynamic tumor landscape. Therefore, new tools are urgently required for accurate tracking of tumor dynamics to enhance cancer prognosis. Liquidbiopsy (LB) can serve as a routine, minimally invasive clinical tool for accurate diagnosis of cancer. Although, the circulating biomarkers in LB better represent the tumor heterogeneity, while being economical and easily applicable in clinical setting for practical patient care; existing LB faces many challenges with pre-analytical preprocessing of biomarkers resulting in biomarker degradation, poor diagnostic accuracy, and long turnaround time. To overcome the existing barriers of LB, I have developed an ultrasensitive sensor for the detection of rare signals of CSC associated bioactive material in circulation. I initiated this research by design and optimization of miniature sized (sub 10 nm) probes for in-vitro biological applications. Next, I employed CSCs-based diagnostic approach because CSCs demonstrate unique characteristics such as self-renewal, tumor initiation, differentiation, and propagation. Prediction of CSC fate by revealing the trajectory of cancer prognosis was undertaken for the first time. Lastly, I demonstrated that the probes, were capable of detection of cancer directly from plasma without extraction or purification of biomarkers. The simplicity of sample processing retainsthe authenticityofcirculatingtumor content,minimizing the source oferrors.The quantum probe platform can provide results in about 60 minutes after blood withdrawal from patients. This diagnostic modality was validated with conventional assays. In this dissertation, CSC associated circulating biomarkers for liquid biopsy are developed,advancing the modality towardsclinical translation.

show abstract

“…The complexity of the testing process requires sophisticated laboratory equipment, highly trained medical personnel, and prolonged processing time (days, even weeks). These limitations have led to skepticism regarding the clinical utility of this technology 64 .…”

Section: Ultra-sensitive Sensor and Multiplex Analysis For Dynamic Ch...mentioning

confidence: 99%

A New Approach Towards Non-Invasive Cancer Diagnostics – Discerning Cancer Stem Cell Signatures in Blood with Self-Functionalized Quantum Sensor Probes

Haldavnekar

2024

Preprint

0

View full text Add to dashboard Cite

This dissertation describes the development of liquid biopsy using the signals of cancer stem cells (CSCs) in blood as a standalone diagnostic modality. Considering the complexity of cancer, it is necessary to capture the tumour-heterogeneity for robust diagnosis. Current state of the art with non-invasive methods relying on imaging has many limitations such as low sensitivity, inability to identify recurrent tumor or discrimination between primary or metastatic tumors. Since imaging-based diagnosis fails to provide sufficient specificity, tissue biopsyremainstobe thegoldstandardfordefinitive diagnosis. However, tissuebiopsyishighlyinvasive and can only provide a snapshot of the tumor, failing to capture the dynamic tumor landscape. Therefore, new tools are urgently required for accurate tracking of tumor dynamics to enhance cancer prognosis. Liquidbiopsy (LB) can serve as a routine, minimally invasive clinical tool for accurate diagnosis of cancer. Although, the circulating biomarkers in LB better represent the tumor heterogeneity, while being economical and easily applicable in clinical setting for practical patient care; existing LB faces many challenges with pre-analytical preprocessing of biomarkers resulting in biomarker degradation, poor diagnostic accuracy, and long turnaround time. To overcome the existing barriers of LB, I have developed an ultrasensitive sensor for the detection of rare signals of CSC associated bioactive material in circulation. I initiated this research by design and optimization of miniature sized (sub 10 nm) probes for in-vitro biological applications. Next, I employed CSCs-based diagnostic approach because CSCs demonstrate unique characteristics such as self-renewal, tumor initiation, differentiation, and propagation. Prediction of CSC fate by revealing the trajectory of cancer prognosis was undertaken for the first time. Lastly, I demonstrated that the probes, were capable of detection of cancer directly from plasma without extraction or purification of biomarkers. The simplicity of sample processing retainsthe authenticityofcirculatingtumor content,minimizing the source oferrors.The quantum probe platform can provide results in about 60 minutes after blood withdrawal from patients. This diagnostic modality was validated with conventional assays. In this dissertation, CSC associated circulating biomarkers for liquid biopsy are developed,advancing the modality towardsclinical translation.

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Rescue of Non-Informative Circulating Tumor DNA to Monitor the Mutational Landscape in NSCLC

Cited by 4 publications

References 28 publications

Circulating-tumour DNA methylation of HAND1 gene: a promising biomarker in early detection of colorectal cancer

Circulating-tumour DNA methylation of HAND1 gene: a promising biomarker in early detection of colorectal cancer

A New Approach Towards Non-Invasive Cancer Diagnostics – Discerning Cancer Stem Cell Signatures in Blood with Self-Functionalized Quantum Sensor Probes

A New Approach Towards Non-Invasive Cancer Diagnostics – Discerning Cancer Stem Cell Signatures in Blood with Self-Functionalized Quantum Sensor Probes

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