Skip to main content
Erschienen in: Die Pathologie 3/2023

24.11.2023 | Hauptreferate: Hauptprogramm der DGP

Using proteomics for stratification and risk prediction in patients with solid tumors

verfasst von: Tilman Werner, Matthias Fahrner, Prof. Dr. Oliver Schilling

Erschienen in: Die Pathologie | Sonderheft 3/2023

Einloggen, um Zugang zu erhalten

Abstract

Proteomics, the study of proteins and their functions, has greatly evolved due to advances in analytical chemistry and computational biology. Unlike genomics or transcriptomics, proteomics captures the dynamic and diverse nature of proteins, which play crucial roles in cellular processes. This is exemplified in cancer, where genomic and transcriptomic information often falls short in reflecting actual protein expression and interactions. Liquid chromatography–mass spectrometry (LC-MS) is pivotal in proteomic data generation, enabling high-throughput analysis of protein samples. The MS-based workflow involves protein digestion, chromatographic separation, ionization, and fragmentation, leading to peptide identification and quantification. Computational biostatistics, particularly using tools in R (R Foundation for Statistical Computing, Vienna, Austria; www.​R-project.​org), aid in data analysis, revealing protein expression patterns and correlations with clinical variables. Proteomic studies can be explorative, aiming to characterize entire proteomes, or targeted, focusing on specific proteins of interest. The integration of proteomics with genomics addresses database limitations and enhances peptide identification. Case studies in intrahepatic cholangiocarcinoma, glioblastoma multiforme, and pancreatic ductal adenocarcinoma highlight proteomics’ clinical applications, from subtyping cancers to identifying diagnostic markers. Moreover, proteomic data augment molecular tumor boards by providing deeper insights into pathway activities and genomic mutations, supporting personalized treatment decisions. Overall, proteomics contributes significantly to advancing our understanding of cellular biology and improving clinical care.
Literatur
1.
Zurück zum Zitat Aebersold R, Mann M (2016) Mass-spectrometric exploration of proteome structure and function. Nature 537:347–355CrossRefPubMed Aebersold R, Mann M (2016) Mass-spectrometric exploration of proteome structure and function. Nature 537:347–355CrossRefPubMed
2.
Zurück zum Zitat Banales JM, Marin JJG, Lamarca A et al (2020) Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol 17:557–588CrossRefPubMedPubMedCentral Banales JM, Marin JJG, Lamarca A et al (2020) Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol 17:557–588CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Chen C, Hou J, Tanner JJ, Cheng J (2020) Bioinformatics methods for mass spectrometry-based proteomics data analysis. Int J Mol Sci 21:2873CrossRefPubMedPubMedCentral Chen C, Hou J, Tanner JJ, Cheng J (2020) Bioinformatics methods for mass spectrometry-based proteomics data analysis. Int J Mol Sci 21:2873CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Chen G, Gharib TG, Huang C‑C et al (2002) Discordant protein and mRNA expression in lung adenocarcinomas. Mol Cell Proteomics 1:304–313CrossRefPubMed Chen G, Gharib TG, Huang C‑C et al (2002) Discordant protein and mRNA expression in lung adenocarcinomas. Mol Cell Proteomics 1:304–313CrossRefPubMed
6.
Zurück zum Zitat Coscia F, Lengyel E, Duraiswamy J et al (2018) Multi-level Proteomics identifies CT45 as a chemosensitivity mediator and immunotherapy target in ovarian cancer. Cell 175:159–170.e16CrossRefPubMedPubMedCentral Coscia F, Lengyel E, Duraiswamy J et al (2018) Multi-level Proteomics identifies CT45 as a chemosensitivity mediator and immunotherapy target in ovarian cancer. Cell 175:159–170.e16CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Demichev V, Szyrwiel L, Yu F et al (2022) dia-PASEF data analysis using fragpipe and DIA-NN for deep proteomics of low sample amounts. Nat Commun 13:3944CrossRefPubMedPubMedCentral Demichev V, Szyrwiel L, Yu F et al (2022) dia-PASEF data analysis using fragpipe and DIA-NN for deep proteomics of low sample amounts. Nat Commun 13:3944CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Doll S, Kriegmair MC, Santos A et al (2018) Rapid proteomic analysis for solid tumors reveals LSD1 as a drug target in an end-stage cancer patient. Mol Oncol 12:1296–1307CrossRefPubMedPubMedCentral Doll S, Kriegmair MC, Santos A et al (2018) Rapid proteomic analysis for solid tumors reveals LSD1 as a drug target in an end-stage cancer patient. Mol Oncol 12:1296–1307CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Doroshow DB, Bhalla S, Beasley MB et al (2021) PD-L1 as a biomarker of response to immune-checkpoint inhibitors. Nat Rev Clin Oncol 18:345–362CrossRefPubMed Doroshow DB, Bhalla S, Beasley MB et al (2021) PD-L1 as a biomarker of response to immune-checkpoint inhibitors. Nat Rev Clin Oncol 18:345–362CrossRefPubMed
10.
Zurück zum Zitat Fröhlich K, Brombacher E, Fahrner M et al (2022) Benchmarking of analysis strategies for data-independent acquisition proteomics using a large-scale dataset comprising inter-patient heterogeneity. Nat Commun 13:2622CrossRefPubMedPubMedCentral Fröhlich K, Brombacher E, Fahrner M et al (2022) Benchmarking of analysis strategies for data-independent acquisition proteomics using a large-scale dataset comprising inter-patient heterogeneity. Nat Commun 13:2622CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Gillet LC, Leitner A, Aebersold R (2016) Mass spectrometry applied to bottom-up proteomics: entering the high-throughput era for hypothesis testing. Annu Rev Anal Chem 9:449–472CrossRef Gillet LC, Leitner A, Aebersold R (2016) Mass spectrometry applied to bottom-up proteomics: entering the high-throughput era for hypothesis testing. Annu Rev Anal Chem 9:449–472CrossRef
13.
Zurück zum Zitat Hoefflin R, Geißler A‑L, Fritsch R et al (2018) Personalized clinical decision making through implementation of a molecular tumor board: a German single-center experience. JCO Precis Oncol (1–16) Hoefflin R, Geißler A‑L, Fritsch R et al (2018) Personalized clinical decision making through implementation of a molecular tumor board: a German single-center experience. JCO Precis Oncol (1–16)
14.
Zurück zum Zitat Jones DTW, Kocialkowski S, Liu L et al (2008) Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas. Cancer Res 68:8673–8677CrossRefPubMedPubMedCentral Jones DTW, Kocialkowski S, Liu L et al (2008) Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas. Cancer Res 68:8673–8677CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Landrum MJ, Lee JM, Riley GR et al (2014) ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res 42:D980–D985CrossRefPubMed Landrum MJ, Lee JM, Riley GR et al (2014) ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res 42:D980–D985CrossRefPubMed
16.
Zurück zum Zitat Larson KL, Huang B, Weiss HL et al (2021) Clinical outcomes of molecular tumor boards: a systematic review. JCO Precis Oncol (1122–1132) Larson KL, Huang B, Weiss HL et al (2021) Clinical outcomes of molecular tumor boards: a systematic review. JCO Precis Oncol (1122–1132)
17.
Zurück zum Zitat Liu Y, Beyer A, Aebersold R (2016) On the dependency of cellular protein levels on mRNA abundance. Cell 165:535–550CrossRefPubMed Liu Y, Beyer A, Aebersold R (2016) On the dependency of cellular protein levels on mRNA abundance. Cell 165:535–550CrossRefPubMed
18.
Zurück zum Zitat Luchini C, Lawlor RT, Milella M, Scarpa A (2020) Molecular tumor boards in clinical practice. Trends Cancer 6:738–744CrossRefPubMed Luchini C, Lawlor RT, Milella M, Scarpa A (2020) Molecular tumor boards in clinical practice. Trends Cancer 6:738–744CrossRefPubMed
19.
Zurück zum Zitat Mani DR, Krug K, Zhang B et al (2022) Cancer proteogenomics: current impact and future prospects. Nat Rev Cancer 22:298–313CrossRefPubMed Mani DR, Krug K, Zhang B et al (2022) Cancer proteogenomics: current impact and future prospects. Nat Rev Cancer 22:298–313CrossRefPubMed
20.
Zurück zum Zitat Organisation mondiale de la santé (2021) Centre international de recherche sur le cancer. In: Central nervous system tumours, 5th edn. International agency for research on cancer, Lyon Organisation mondiale de la santé (2021) Centre international de recherche sur le cancer. In: Central nervous system tumours, 5th edn. International agency for research on cancer, Lyon
21.
22.
Zurück zum Zitat Schwaederle M, Parker BA, Schwab RB et al (2014) Molecular tumor board: the university of california san diego moores cancer center experience. The Oncol 19:631–636CrossRef Schwaederle M, Parker BA, Schwab RB et al (2014) Molecular tumor board: the university of california san diego moores cancer center experience. The Oncol 19:631–636CrossRef
23.
Zurück zum Zitat Schwanhäusser B, Busse D, Li N et al (2011) Global quantification of mammalian gene expression control. Nature 473:337–342CrossRefPubMed Schwanhäusser B, Busse D, Li N et al (2011) Global quantification of mammalian gene expression control. Nature 473:337–342CrossRefPubMed
24.
Zurück zum Zitat Sharma K, D’Souza RCJ, Tyanova S et al (2014) Ultradeep human phosphoproteome reveals a distinct regulatory nature of tyr and Ser/Thr-based signaling. Cell Rep 8:1583–1594CrossRefPubMed Sharma K, D’Souza RCJ, Tyanova S et al (2014) Ultradeep human phosphoproteome reveals a distinct regulatory nature of tyr and Ser/Thr-based signaling. Cell Rep 8:1583–1594CrossRefPubMed
25.
Zurück zum Zitat Tan HT, Lee YH, Chung MCM (2012) Cancer proteomics: CANCER PROTEOMICS. Mass Spectrom Rev 31:583–605CrossRefPubMed Tan HT, Lee YH, Chung MCM (2012) Cancer proteomics: CANCER PROTEOMICS. Mass Spectrom Rev 31:583–605CrossRefPubMed
26.
Zurück zum Zitat Vidova V, Spacil Z (2017) A review on mass spectrometry-based quantitative proteomics: targeted and data independent acquisition. Anal Chim Acta 964:7–23CrossRefPubMed Vidova V, Spacil Z (2017) A review on mass spectrometry-based quantitative proteomics: targeted and data independent acquisition. Anal Chim Acta 964:7–23CrossRefPubMed
27.
Zurück zum Zitat Werner J, Bernhard P, Cosenza-Contreras M et al (2023) Targeted and explorative profiling of kallikrein proteases and global proteome biology of pancreatic ductal adenocarcinoma, chronic pancreatitis, and normal pancreas highlights disease-specific proteome remodelling. Neoplasia 36:100871CrossRefPubMedPubMedCentral Werner J, Bernhard P, Cosenza-Contreras M et al (2023) Targeted and explorative profiling of kallikrein proteases and global proteome biology of pancreatic ductal adenocarcinoma, chronic pancreatitis, and normal pancreas highlights disease-specific proteome remodelling. Neoplasia 36:100871CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Witze ES, Old WM, Resing KA, Ahn NG (2007) Mapping protein post-translational modifications with mass spectrometry. Nat Methods 4:798–806CrossRefPubMed Witze ES, Old WM, Resing KA, Ahn NG (2007) Mapping protein post-translational modifications with mass spectrometry. Nat Methods 4:798–806CrossRefPubMed
29.
Zurück zum Zitat Zhu Y, Aebersold R, Mann M, Guo T (2021) SnapShot: Clinical proteomics. Cell 184:4840–4840.e1CrossRefPubMed Zhu Y, Aebersold R, Mann M, Guo T (2021) SnapShot: Clinical proteomics. Cell 184:4840–4840.e1CrossRefPubMed
Metadaten
Titel
Using proteomics for stratification and risk prediction in patients with solid tumors
verfasst von
Tilman Werner
Matthias Fahrner
Prof. Dr. Oliver Schilling
Publikationsdatum
24.11.2023
Verlag
Springer Medizin
Erschienen in
Die Pathologie / Ausgabe Sonderheft 3/2023
Print ISSN: 2731-7188
Elektronische ISSN: 2731-7196
DOI
https://doi.org/10.1007/s00292-023-01261-x

Weitere Artikel der Sonderheft 3/2023

Die Pathologie 3/2023 Zur Ausgabe

Hauptreferate: Arbeitsgemeinschaften der DGP – Kurzbeiträge

Digitale Pathologie in Österreich

Hauptreferate: Arbeitsgemeinschaften der DGP – Kurzbeiträge

National digital pathology projects in Switzerland: A 2023 update

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Bei seelischem Stress sind Checkpoint-Hemmer weniger wirksam

03.06.2024 NSCLC Nachrichten

Wie stark Menschen mit fortgeschrittenem NSCLC von einer Therapie mit Immun-Checkpoint-Hemmern profitieren, hängt offenbar auch davon ab, wie sehr die Diagnose ihre psychische Verfassung erschüttert

Antikörper mobilisiert Neutrophile gegen Krebs

03.06.2024 Onkologische Immuntherapie Nachrichten

Ein bispezifischer Antikörper formiert gezielt eine Armee neutrophiler Granulozyten gegen Krebszellen. An den Antikörper gekoppeltes TNF-alpha soll die Zellen zudem tief in solide Tumoren hineinführen.

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

29.05.2024 Larynxkarzinom Nachrichten

Fast ein Viertel der Personen mit mäßig dysplastischen Stimmlippenläsionen entwickelt einen Kehlkopftumor. Solche Personen benötigen daher eine besonders enge ärztliche Überwachung.

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

29.05.2024 Herzinfarkt Nachrichten

Bei Menschen mit Typ-2-Diabetes sind die Chancen, einen Myokardinfarkt zu überleben, in den letzten 15 Jahren deutlich gestiegen – nicht jedoch bei Betroffenen mit Typ 1.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.