Proteomic Profiling in Colorectal Cancer: Identifying Druggable Biomarkers for Personalized Therapy

Abdulkadir Elmas

doi:10.31466/kfbd.1608816

EN TR

Proteomic Profiling in Colorectal Cancer: Identifying Druggable Biomarkers for Personalized Therapy

Abstract

Colorectal cancer (CRC) remains a major global health challenge, with limited treatment options for advanced-stage patients. While genomic and transcriptomic analyses aid in target identification, proteomic alterations offer a more direct link to tumor biology and therapeutic opportunities. In this study, we analyzed mass spectrometry-based proteomics data from 102 primary CRC patients, including tumor and matched normal tissues, to systematically identify overexpressed, druggable therapeutic targets, with a particular focus on the patient kinome. Using the OPPTI approach, we discovered 31 kinases with notable overexpression, including 16 currently targetable by existing drugs, such as FGR, EPHA2, and PBK. Furthermore, we revealed 884 overexpressed non-kinase proteins, 253 of which are druggable, including ERAP2, FLG, and MT1H. Differential expression analysis identified 165 dysregulated kinases and 3,903 non-kinase proteins, with MET and STK3 emerging as potential candidates due to their substantial upregulation. Integrating differential expression and overexpression analyses, we highlighted a cohort of druggable targets, including EPHA2 and MET, whose inhibition has shown promising preclinical efficacy. This comprehensive proteomic study provides a resource for novel therapeutic target discovery in CRC, offering a framework for more personalized interventions through the identification of clinically actionable protein-level alterations.

Keywords

Colorectal cancer (CRC), Proteomics, Personalized therapy, Drug targets, Tumor biomarkers

Kolorektal Kanserin Proteomik Profili: Kişiselleştirilmiş Tedavi için İlaçlanabilir Biyobelirteçlerin Keşfi

Abstract

Kolorektal kanser (CRC), ileri evre hastalar için sınırlı tedavi seçenekleri nedeniyle küresel ölçekte önemli bir sağlık sorunu olmaya devam etmektedir. Genomik ve transkriptomik analizler hedef belirlemede değerli bir rol oynasa da, proteomik düzeydeki değişimler tümör biyolojisini daha doğrudan yansıtmakta ve terapötik açıdan daha uygulanabilir fırsatlar sunmaktadır. Bu çalışmada, 102 birincil CRC hastasına ait, tümör ve eşlenmiş normal dokuları içeren kütle spektrometresi proteomik verilerini analiz ederek, hasta kinomu üzerine odaklanarak sistematik bir şekilde aşırı ifade (eksprese) edilen, ilaçlanabilir terapötik hedefleri tanımladık. OPPTI metodunu kullanarak, mevcut ilaçlarla hedeflenebilir olan FGR, EPHA2 ve PBK gibi 16 kinazı içeren, toplamda 31 kinazın belirgin şekilde aşırı ifade edildiğini tespit ettik. Ayrıca, ERAP2, FLG ve MT1H gibi 253’ü ilaçlanabilir olan 884 kinaz dışı proteinin aşırı ifade edildiğini ortaya koyduk. Diferansiyel ifade analizi, 165 düzensiz kinaz ve 3,903 kinaz dışı proteini belirlerken, MET ve STK3, önemli derecede artış gösteren potansiyel adaylar olarak öne çıktı. Diferansiyel ifade ve aşırı ifade analizlerini birleştirerek, EPHA2 ve MET gibi ilaçlanabilir hedeflerden oluşan bir grup belirledik; bu hedeflerin inhibisyonu, umut verici preklinik etkinlik göstermiştir. Bu kapsamlı proteomik çalışma, CRC’de yeni terapötik hedeflerin keşfi için bir kaynak sunmakta ve klinik olarak uygulanabilir protein düzeyindeki değişikliklerin tanımlanması yoluyla daha kişiselleştirilmiş müdahalelere yönelik bir çerçeve sağlamaktadır.

Keywords

Kolorektal kanser (CRC), Proteomik analiz, Kişiselleştirilmiş tedavi, İlaç hedefleri, Tümör biyobelirteçleri

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Details

Primary Language

English

Subjects

Biomedical Therapy

Journal Section

Research Article

Authors

Abdulkadir Elmas ^*
0000-0002-7999-5770
Türkiye

Publication Date

March 15, 2025

Submission Date

December 28, 2024

Acceptance Date

March 2, 2025

Published in Issue

Year 2025 Volume: 15 Number: 1

DOI

https://doi.org/10.31466/kfbd.1608816

IZ

https://izlik.org/JA63CY98BM

APA

Elmas, A. (2025). Proteomic Profiling in Colorectal Cancer: Identifying Druggable Biomarkers for Personalized Therapy. Karadeniz Fen Bilimleri Dergisi, 15(1), 519-535. https://doi.org/10.31466/kfbd.1608816

AMA

1.Elmas A. Proteomic Profiling in Colorectal Cancer: Identifying Druggable Biomarkers for Personalized Therapy. KFBD. 2025;15(1):519-535. doi:10.31466/kfbd.1608816

Chicago

Elmas, Abdulkadir. 2025. “Proteomic Profiling in Colorectal Cancer: Identifying Druggable Biomarkers for Personalized Therapy”. Karadeniz Fen Bilimleri Dergisi 15 (1): 519-35. https://doi.org/10.31466/kfbd.1608816.

EndNote

Elmas A (March 1, 2025) Proteomic Profiling in Colorectal Cancer: Identifying Druggable Biomarkers for Personalized Therapy. Karadeniz Fen Bilimleri Dergisi 15 1 519–535.

IEEE

[1]A. Elmas, “Proteomic Profiling in Colorectal Cancer: Identifying Druggable Biomarkers for Personalized Therapy”, KFBD, vol. 15, no. 1, pp. 519–535, Mar. 2025, doi: 10.31466/kfbd.1608816.

ISNAD

Elmas, Abdulkadir. “Proteomic Profiling in Colorectal Cancer: Identifying Druggable Biomarkers for Personalized Therapy”. Karadeniz Fen Bilimleri Dergisi 15/1 (March 1, 2025): 519-535. https://doi.org/10.31466/kfbd.1608816.

JAMA

1.Elmas A. Proteomic Profiling in Colorectal Cancer: Identifying Druggable Biomarkers for Personalized Therapy. KFBD. 2025;15:519–535.

MLA

Elmas, Abdulkadir. “Proteomic Profiling in Colorectal Cancer: Identifying Druggable Biomarkers for Personalized Therapy”. Karadeniz Fen Bilimleri Dergisi, vol. 15, no. 1, Mar. 2025, pp. 519-35, doi:10.31466/kfbd.1608816.

Vancouver

1.Abdulkadir Elmas. Proteomic Profiling in Colorectal Cancer: Identifying Druggable Biomarkers for Personalized Therapy. KFBD. 2025 Mar. 1;15(1):519-35. doi:10.31466/kfbd.1608816

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Proteomic Profiling in Colorectal Cancer: Identifying Druggable Biomarkers for Personalized Therapy

Abstract

Keywords

Kolorektal Kanserin Proteomik Profili: Kişiselleştirilmiş Tedavi için İlaçlanabilir Biyobelirteçlerin Keşfi

Abstract

Keywords

References

Details

Primary Language

Subjects

Journal Section

Authors

Publication Date

Submission Date

Acceptance Date

Published in Issue

DOI

IZ

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