Proteomic analysis of brain metastatic lung adenocarcinoma reveals intertumoral heterogeneity and specific alterations associated with the timing of brain metastases

Woldmar, Nicole; Schwendenwein, Anna; Kuras, Magdalena; Szeitz, Beáta; Boettiger, Kristiina; Tisza, Anna; László, Viktória; Reiniger, Lilla; Bagó, Attila G.; Szállási, Zoltán; Moldvay, Judit; Szász, Attila Marcell; Malm, Johan; Horvatovich, Péter; Pizzatti, Luciana; Domont, Gilberto B.; Rényi-Vámos, F; Höetzenecker, Konrad; Hoda, Mir Alireza; Markó-Varga, György; Schelch, Karin; Rezeli, Melinda; Döme, Balázs

doi:10.1016/j.esmoop.2022.100741

Cited by 8 publications

(9 citation statements)

References 93 publications

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“…These subsets bore significant prognostic associations in advanced NSCLC, indicating their prospective utility as monitoring tools in NSCLC brain metastases therapeutic paradigms. On the serological front, proteomics emerges as a promising avenue for the early detection and surveillance of NSCLC brain metastases patients [143]. A few previous studies have drawn correlations between pretreatment serum carcinoembryonic antigen (CEA) levels and brain metastasis in advanced NSCLC [144].…”

Section: Immune Cells and Serological Biomarkersmentioning

confidence: 99%

Exploring the Molecular Tumor Microenvironment and Translational Biomarkers in Brain Metastases of Non-Small-Cell Lung Cancer

Wen,

Yu,

Liu

et al. 2024

IJMS

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Brain metastases represent a significant clinical challenge in the treatment of non-small-cell lung cancer (NSCLC), often leading to a severe decline in patient prognosis and survival. Recent advances in imaging and systemic treatments have increased the detection rates of brain metastases, yet clinical outcomes remain dismal due to the complexity of the metastatic tumor microenvironment (TME) and the lack of specific biomarkers for early detection and targeted therapy. The intricate interplay between NSCLC tumor cells and the surrounding TME in brain metastases is pivotal, influencing tumor progression, immune evasion, and response to therapy. This underscores the necessity for a deeper understanding of the molecular underpinnings of brain metastases, tumor microenvironment, and the identification of actionable biomarkers that can inform multimodal treatment approaches. The goal of this review is to synthesize current insights into the TME and elucidate molecular mechanisms in NSCLC brain metastases. Furthermore, we will explore the promising horizon of emerging biomarkers, both tissue- and liquid-based, that hold the potential to radically transform the treatment strategies and the enhancement of patient outcomes.

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Section: Immune Cells and Serological Biomarkersmentioning

confidence: 99%

Exploring the Molecular Tumor Microenvironment and Translational Biomarkers in Brain Metastases of Non-Small-Cell Lung Cancer

Wen,

Yu,

Liu

et al. 2024

IJMS

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“…[1,53] Therefore, brain metastases and their original primary tumors appear similar at a pathological level, and the histological appearance of brain metastases usually resembles that of primary tumors, however, their biological and genetic characteristics can be significantly different. [13,28,62] When metastatic tumor cells reach the brain, they encounter a complex microenvironment that is drastically different from the ecological environment at the primary site. Various types of cells, including neurons, astrocytes, and microglia, constitute the special microenvironment of the brain, which are not present in the extracranial organs from which primary tumors originate.…”

Section: Special Pathophysiology Characteristicsmentioning

confidence: 99%

Section: The Origins and Treatment Challenges Of Brain Metastasismentioning

confidence: 99%

“…[1,7,11] A considerable number of cancer patients who have developed brain metastases are asymptomatic for a long time; alternatively, they miss the timely detection of brain metastases due to lack of specialized and sensitive diagnostic techniques when they have typical but not severe symptoms. [12,13] Even in patients with severe cancer symptoms at the primary site, failure in identifying the symptoms of brain metastases can lead to delayed diagnosis and treatment. Without timely diagnosis and treatment during the clinical period, patients with brain metastases ultimately become dead.…”

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confidence: 99%

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Challenges and Opportunities of Nanomedicine: Novel Comprehensive Approaches for Brain Metastasis

Xiang,

Li,

Pan

et al. 2023

Small Structures

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Brain metastasis is the leading cause of death in most cancer patients; thus, anti‐brain metastasis is a crucial step in cancer treatment. The unique microenvironment and pathophysiological characteristics of brain metastases hamper the development of effective treatment methods, while the advances in nanomedicine demonstrate its immense potential for addressing this challenge. In recent years, due to breakthroughs in nanotechnology, functional and complex nanomedicine is prepared and it has been extensively explored to improve the treatment of brain metastasis. Compared to traditional treatment methods, nanomedicine can combine multiple traditional treatment methods into one single medicinal format and target unique characteristics of brain metastases to enhance the treatment efficacy. This review summarizes the main obstacles in the field of brain metastasis treatment and clinical/preclinical studies and surveys the use of a variety of nanomedicine candidates as antibrain metastasis strategies for different types of brain metastases.

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“…Each stage of the bottom-up proteomic workflow has tremendously developed over the last two decades. The development of high-performance liquid chromatography (HPLC) instrumentation over the past decade has facilitated proteomic research by simultaneously separating many peptides in a single run [ 19 , 20 ]. Reversed-phase liquid chromatography (RPLC) plays a critical role in protein/peptide separation prior to MS/MS analysis [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Bottom-Up Proteomics: Advancements in Sample Preparation

Duong

Lee

2023

IJMS

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Liquid chromatography–tandem mass spectrometry (LC–MS/MS)-based proteomics is a powerful technique for profiling proteomes of cells, tissues, and body fluids. Typical bottom-up proteomic workflows consist of the following three major steps: sample preparation, LC–MS/MS analysis, and data analysis. LC–MS/MS and data analysis techniques have been intensively developed, whereas sample preparation, a laborious process, remains a difficult task and the main challenge in different applications. Sample preparation is a crucial stage that affects the overall efficiency of a proteomic study; however, it is prone to errors and has low reproducibility and throughput. In-solution digestion and filter-aided sample preparation are the typical and widely used methods. In the past decade, novel methods to improve and facilitate the entire sample preparation process or integrate sample preparation and fractionation have been reported to reduce time, increase throughput, and improve reproducibility. In this review, we have outlined the current methods used for sample preparation in proteomics, including on-membrane digestion, bead-based digestion, immobilized enzymatic digestion, and suspension trapping. Additionally, we have summarized and discussed current devices and methods for integrating different steps of sample preparation and peptide fractionation.

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Proteomic analysis of brain metastatic lung adenocarcinoma reveals intertumoral heterogeneity and specific alterations associated with the timing of brain metastases

Cited by 8 publications

References 93 publications

Exploring the Molecular Tumor Microenvironment and Translational Biomarkers in Brain Metastases of Non-Small-Cell Lung Cancer

Exploring the Molecular Tumor Microenvironment and Translational Biomarkers in Brain Metastases of Non-Small-Cell Lung Cancer

Challenges and Opportunities of Nanomedicine: Novel Comprehensive Approaches for Brain Metastasis

Bottom-Up Proteomics: Advancements in Sample Preparation

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