Cell-free DNA methylation-defined prognostic subgroups in small-cell lung cancer identified by leukocyte methylation subtraction

Haq, Sami Ul; Schmid, Sabine; Aparnathi, Mansi K.; Hueniken, Katrina; Zhan, L.; Sacdalan, Danielle Benedict; Li, J.; Meti, Nicholas; Patel, Devalben; Cheng, Dangxiao; Philip, Vivek; Tsao, Ming Sound; Cabanero, Michael; Carvalho, Daniel D De; Liu, Geoffrey; Bratman, Scott V.; Lok, Benjamin H.

doi:10.1016/j.isci.2022.105487

Cited by 7 publications

(3 citation statements)

References 36 publications

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“…Sami UI Haq performed a comprehensive profilation of the methylome of SCLC patients (N=74) on cfDNA, identifying two clusters of methylation with different prognosis. Although the significance value was lost adjusting results for stage, authors stated that the study was not powered to identify stage-independent differences ( 117 ).…”

Section: Methodsmentioning

confidence: 99%

Tissue and circulating biomarkers of benefit to immunotherapy in extensive-stage small cell lung cancer patients

Lorenzi,

Resi,

Bonanno

et al. 2024

Front. Immunol.

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Extensive stage-Small-Cell Lung Cancer (ES-SCLC) is an aggressive cancer with dismal prognosis. The addition of immune-checkpoint inhibitors (ICIs) to platinum-based chemotherapy have been consistently demonstrated to improve outcomes and survival, becoming the new standard in first – line treatment of ES-SCLC patients. However, despite positive results reported in the pivotal trials, longer benefit appears evident only for a selected group of patients. Several predictive biomarkers have been studied so far but the prospective identification of patients more likely to experience better outcome seems to be challenging in SCLC. Indeed, classical immune predictive biomarkers as PD-L1 and tumor mutational burden (TMB) seem not to correlate with outcomes. Recently, a new molecular classification of SCLC based on differential expression of genes associated with specific clinical behaviors and therapeutic vulnerability have been presented suggesting a new field to be investigated. Despite the achievements, these studies focused mainly on inter-tumoral heterogeneity, limiting the exploration of intra-tumoral heterogeneity and cell to cell interactions. New analysis methods are ongoing in order to explore subtypes plasticity. Analysis on single biopsies cannot catch the whole genomic profile and dynamic change of disease over time and during treatment. Moreover, the availability of tissue for translational research is limited due to the low proportion of patients undergoing surgery. In this context, liquid biopsy is a promising tool to detect reliable predictive biomarkers. Here, we reviewed the current available data on predictive role of tissue and liquid biomarkers in ES-SCLC patients receiving ICIs. We assessed latest results in terms of predictive and prognostic value of gene expression profiling in SCLC. Finally, we explored the role of liquid biopsy as a tool to monitor SCLC patients over time.

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Section: Methodsmentioning

confidence: 99%

Tissue and circulating biomarkers of benefit to immunotherapy in extensive-stage small cell lung cancer patients

Lorenzi,

Resi,

Bonanno

et al. 2024

Front. Immunol.

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“…Recognizing that the tumor methylation signal was distinct from that of the non-cancer genome, Ul Haq et al [101] performed a whole genome approach to the assessment of the cell-free methylome of SCLC using cfMeDIP-seq. The authors utilized an in silico approach using paired peripheral blood leukocytes to subtract non-cancer noise from cfDNA methylation data similar to previous studies [71].…”

Section: Methylation As a Prognostic Biomarker Of Patient Outcomesmentioning

confidence: 99%

“…The authors utilized an in silico approach using paired peripheral blood leukocytes to subtract non-cancer noise from cfDNA methylation data similar to previous studies [71]. This approach identified two biologically distinct methylation-defined SCLC prognostic groups with differences in overall survival [101]. Validation of ctDNA methylation as a prognostic biomarker in HNSCC and RCC was performed and data from these studies were presented in abstract form at the ESMO 2023 conference (Table 1) [94,95].…”

Section: Methylation As a Prognostic Biomarker Of Patient Outcomesmentioning

confidence: 99%

Plasma Cell-Free Tumor Methylome as a Biomarker in Solid Tumors: Biology and Applications

Sacdalan,

Ul Haq,

Lok

2024

Current Oncology

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DNA methylation is a fundamental mechanism of epigenetic control in cells and its dysregulation is strongly implicated in cancer development. Cancers possess an extensively hypomethylated genome with focal regions of hypermethylation at CPG islands. Due to the highly conserved nature of cancer-specific methylation, its detection in cell-free DNA in plasma using liquid biopsies constitutes an area of interest in biomarker research. The advent of next-generation sequencing and newer computational technologies have allowed for the development of diagnostic and prognostic biomarkers that utilize methylation profiling to diagnose disease and stratify risk. Methylome-based predictive biomarkers can determine the response to anti-cancer therapy. An additional emerging application of these biomarkers is in minimal residual disease monitoring. Several key challenges need to be addressed before cfDNA-based methylation biomarkers become fully integrated into practice. The first relates to the biology and stability of cfDNA. The second concerns the clinical validity and generalizability of methylation-based assays, many of which are cancer type-specific. The third involves their practicability, which is a stumbling block for translating technologies from bench to clinic. Future work on developing pan-cancer assays with their respective validities confirmed using well-designed, prospective clinical trials is crucial in pushing for the greater use of these tools in oncology.

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Clinical validation of a tissue-agnostic genome-wide methylome enrichment molecular residual disease assay for head and neck malignancies

Liu,

Huang,

Ailles

et al. 2024

Annals of Oncology

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Cell-free DNA methylation-defined prognostic subgroups in small-cell lung cancer identified by leukocyte methylation subtraction

Cited by 7 publications

References 36 publications

Tissue and circulating biomarkers of benefit to immunotherapy in extensive-stage small cell lung cancer patients

Tissue and circulating biomarkers of benefit to immunotherapy in extensive-stage small cell lung cancer patients

Plasma Cell-Free Tumor Methylome as a Biomarker in Solid Tumors: Biology and Applications

Clinical validation of a tissue-agnostic genome-wide methylome enrichment molecular residual disease assay for head and neck malignancies

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