Lung Cancer Proteogenomics: New Era, New Insights

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: 15 July 2025 | Viewed by 6891

Special Issue Editor


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Guest Editor
Division of Biotechnology, Center of Systems Biology, Biomedical Research Foundation of the Academy of Athens (BRFAA), 11525 Athens, Greece
Interests: pediatric brain malignancies; proteins; omics

Special Issue Information

Dear Colleagues,

Lung cancer remains a major public health concern, constituting the second most prevalent malignancy and the leading cause of cancer-related mortality worldwide. Lung cancer incidence and outcomes vary depending on factors such as age, sex, ethnicity, smoking habits, environment, and socioeconomic status. Despite efforts to elucidate its molecular characteristics, it is still largely unknown why lung cancer is becoming the commonest and deadliest of cancers.

Integration of high-throughput molecular data originating from mass spectrometry (proteomics) to those of next-generation sequencing (genomics, transcriptomics) are currently paving the way towards designating molecular causes of cancer tumorigenesis. Proteogenomics is increasingly becoming a valuable instrument for biomedical research. This type of research is important in the lung cancer setting, not only for understanding its epidemiology, but also for studying effective therapeutic strategies in clinical applications.

For this Special Issue, we invite authors to contribute original research articles, method papers, as well as review articles that address recent achievements in proteogenomics associated with lung cancer research.

Potential topics include but are not limited to the following:

  • Methods of genomic, transcriptomic, and proteomic data integration;
  • Bioinformatic tools towards metagenomics and metaproteomics;
  • Clinical lung cancer proteogenomics towards precision medicine;
  • Lung cancer multi-omics.

Dr. Thanasis Anagnostopoulos
Guest Editor

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Keywords

  • lung cancer
  • genomic
  • transcriptomic
  • bioinformatic tools
  • multi-omics

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Published Papers (2 papers)

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26 pages, 12100 KiB  
Article
Molecular Profiling of A549 Cell-Derived Exosomes: Proteomic, miRNA, and Interactome Analysis for Identifying Potential Key Regulators in Lung Cancer
by Alexandros Giannopoulos-Dimitriou, Aikaterini Saiti, Andigoni Malousi, Athanasios K. Anagnostopoulos, Giannis Vatsellas, Passant M. Al-Maghrabi, Anette Müllertz, Dimitrios G. Fatouros and Ioannis S. Vizirianakis
Cancers 2024, 16(24), 4123; https://doi.org/10.3390/cancers16244123 - 10 Dec 2024
Cited by 1 | Viewed by 1876
Abstract
Background/Objectives: Exosomes, nano-sized extracellular vesicles released by all cells, play a key role in intercellular communication and carry tumorigenic properties that impact surrounding or distant cells. The complexity of the exosomal molecular interactome and its effects on recipient cells still remain unclear. This [...] Read more.
Background/Objectives: Exosomes, nano-sized extracellular vesicles released by all cells, play a key role in intercellular communication and carry tumorigenic properties that impact surrounding or distant cells. The complexity of the exosomal molecular interactome and its effects on recipient cells still remain unclear. This study aims to decipher the molecular profile and interactome of lung adenocarcinoma A549 cell-derived exosomes using multi-omics and bioinformatics approaches. Methods: We performed comprehensive morphological and physicochemical characterization of exosomes isolated from cell culture supernatant of A549 cells in vitro, using DLS, cryo-TEM, Western blot, and flow cytometry. Proteomic and miRNA high-throughput profiling, coupled with bioinformatics network analysis, were applied to elucidate the exosome molecular cargo. A comparative miRNA analysis was also conducted with exosomes derived from normal lung fibroblast MRC-5 cells. Results: Exosomes exhibited an average size of ~40 nm and disk-shaped lipid bilayer structures, with tetraspanins CD9 and CD63 validated as exosomal markers. Proteomic analysis identified 68 proteins, primarily linked to the extracellular matrix organization and metabolic processes. miRNA sequencing revealed 72 miRNAs, notably hsa-miR-619-5p, hsa-miR-122-5p, hsa-miR-9901, hsa-miR-7704, and hsa-miR-151a-3p, which are involved in regulating metabolic processes, gene expression, and tumorigenic pathways. Th integration of proteomic and miRNA data through a proteogenomics approach identified dually affected genes including ERBB2, CD44, and APOE, impacted by both exosomal miRNA targeting and protein interactions through synergistic or antagonistic interactions. Differential analysis revealed a distinct miRNA profile in A549 exosomes, associated with cancer-related biological processes, compared to MRC-5 exosomes; notably, hsa-miR-619-5p emerged as a promising candidate for future clinical biomarker studies. The network analysis also revealed genes targeted by multiple upregulated tumor-associated miRNAs in potential exosome-recipient cells. Conclusions: This integrative study provides insights into the molecular interactome of lung adenocarcinoma A549 cell-derived exosomes, providing a foundation for future research on exosomal cargo and its role in tumor cell communication, growth, and progression. Full article
(This article belongs to the Special Issue Lung Cancer Proteogenomics: New Era, New Insights)
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17 pages, 2544 KiB  
Systematic Review
Lung Cancer Proteogenomics: Shaping the Future of Clinical Investigation
by Theofanis Vavilis, Maria Louiza Petre, Giannis Vatsellas, Alexandra Ainatzoglou, Eleni Stamoula, Athanasios Sachinidis, Malamatenia Lamprinou, Ioannis Dardalas, Ioannis N. Vamvakaris, Ioannis Gkiozos, Konstantinos N. Syrigos and Athanasios K. Anagnostopoulos
Cancers 2024, 16(6), 1236; https://doi.org/10.3390/cancers16061236 - 21 Mar 2024
Cited by 1 | Viewed by 4104
Abstract
Background: Lung cancer is associated with a high incidence of mortality worldwide. Molecular mechanisms governing the disease have been explored by genomic studies; however, several aspects remain elusive. The integration of genomic profiling with in-depth proteomic profiling has introduced a new dimension to [...] Read more.
Background: Lung cancer is associated with a high incidence of mortality worldwide. Molecular mechanisms governing the disease have been explored by genomic studies; however, several aspects remain elusive. The integration of genomic profiling with in-depth proteomic profiling has introduced a new dimension to lung cancer research, termed proteogenomics. The aim of this review article was to investigate proteogenomic approaches in lung cancer, focusing on how elucidation of proteogenomic features can evoke tangible clinical outcomes. Methods: A strict methodological approach was adopted for study selection and key article features included molecular attributes, tumor biomarkers, and major hallmarks involved in oncogenesis. Results: As a consensus, in all studies it becomes evident that proteogenomics is anticipated to fill significant knowledge gaps and assist in the discovery of novel treatment options. Genomic profiling unravels patient driver mutations, and exploration of downstream effects uncovers great variability in transcript and protein correlation. Also, emphasis is placed on defining proteogenomic traits of tumors of major histological classes, generating a diverse portrait of predictive markers and druggable targets. Conclusions: An up-to-date synthesis of landmark lung cancer proteogenomic studies is herein provided, underpinning the importance of proteogenomics in the landscape of personalized medicine for combating lung cancer. Full article
(This article belongs to the Special Issue Lung Cancer Proteogenomics: New Era, New Insights)
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