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

Abdulkadir Elmas

Makale detayları

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

Yazarlar:

Abdulkadir Elmas

Yayıncı:

Giresun University

Ana Başlıklar:

Biyomedikal Terapi

Dergi:

Karadeniz Fen Bilimleri Dergisi Vol.15 Issue 1, pp.519-535

Belge Tipi:

Makale

Yayın Tarihi:

3/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001342328

pISSN:

2564-7377

Anahtar kelimeler:

Özet:

 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.

 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.

 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.

 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 253ü 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, CRCde yeni terapötik hedeflerin keşfi için bir kaynak sunmakta ve klinik olarak uygulanabilir protein düzeyindeki değişikliklerin tanımlanması yoluyla daha kişiselleştirilmiş müdahalelere yönelik bir çerçeve sağlamaktadır.

Makale detayları

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

Yazarlar:

Abdulkadir Elmas

Yayıncı:

Giresun University

Ana Başlıklar:

Biyomedikal Terapi

Dergi:

Karadeniz Fen Bilimleri Dergisi Vol.15 Issue 1, pp.519-535

Belge Tipi:

Makale

Yayın Tarihi:

3/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001342328

pISSN:

2564-7377

Colorectal cancer (CRC)

Proteomics

Personalized therapy

Drug targets

Tumor biomarkersKolorektal kanser (CRC)

Proteomik analiz

Kişiselleştirilmiş tedavi

İlaç hedefleri

Tümör biyobelirteçleri

Sayı

Makale detayları

Yazarlar: Abdulkadir Elmas

Yayıncı: Giresun University

Ana Başlıklar: Biyomedikal Terapi

Dergi: Karadeniz Fen Bilimleri Dergisi Vol.15 Issue 1, pp.519-535

Belge Tipi: Makale

Yayın Tarihi: 3/2025

Belge Dili: İngilizce

Document ID (Org No.): 2001342328

pISSN: 2564-7377

Sayı

Yazarlar:

Abdulkadir Elmas

Yayıncı:

Giresun University

Ana Başlıklar:

Biyomedikal Terapi

Dergi:

Karadeniz Fen Bilimleri Dergisi Vol.15 Issue 1, pp.519-535

Belge Tipi:

Makale

Yayın Tarihi:

3/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001342328

pISSN:

2564-7377