Profiling Kinase Activities for Precision Oncology in Diffuse Gastric Cancer
Gastric cancer (GC) remains a leading cause of cancer-related mortality globally. This is due to the fact that majority of the cases of GC are diagnosed at an advanced stage when the treatment options are limited and prognosis is poor. The diffuse subtype of gastric cancer (DGC) under Lauren's classification is more aggressive and usually occurs in younger patients than the intestinal subtype. The concept of personalized medicine is leading to the identification of multiple biomarkers in a large variety of cancers using different combinations of omics technologies. Proteomic changes including post-translational modifications are crucial in oncogenesis. We analyzed the phosphoproteome of DGC by using paired fresh frozen tumor and adjacent normal tissue from five patients diagnosed with DGC. We found proteins involved in the epithelial-to-mesenchymal transition (EMT), c-MYC pathway, and semaphorin pathways to be differentially phosphorylated in DGC tissues. We identified three kinases, namely, bromodomain adjacent to the zinc finger domain 1B (BAZ1B), WNK lysine-deficient protein kinase 1 (WNK1), and myosin light-chain kinase (MLCK) to be hyperphosphorylated, and one kinase, AP2-associated protein kinase 1 (AAK1), to be hypophosphorylated. LMNA hyperphosphorylation at serine 392 (S392) was demonstrated in DGC using immunohistochemistry. Importantly, we have detected heparin-binding growth factor (HDGF), heat shock protein 90 (HSP90), and FTH1 as potential therapeutic targets in DGC, as drugs targeting these proteins are currently under investigation in clinical trials. Although these new findings need to be replicated in larger study samples, they advance our understanding of signaling alterations in DGC, which could lead to potentially novel actionable targets in GC.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:28 |
|---|---|
| Enthalten in: |
Omics : a journal of integrative biology - 28(2024), 2 vom: 16. Feb., Seite 76-89 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Singh, Smrita [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 16.02.2024 Date Revised 16.02.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1089/omi.2023.0173 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM367619792 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM367619792 | ||
| 003 | DE-627 | ||
| 005 | 20240216232746.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240126s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1089/omi.2023.0173 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1295.xml |
| 035 | |a (DE-627)NLM367619792 | ||
| 035 | |a (NLM)38271566 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Singh, Smrita |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Profiling Kinase Activities for Precision Oncology in Diffuse Gastric Cancer |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 16.02.2024 | ||
| 500 | |a Date Revised 16.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Gastric cancer (GC) remains a leading cause of cancer-related mortality globally. This is due to the fact that majority of the cases of GC are diagnosed at an advanced stage when the treatment options are limited and prognosis is poor. The diffuse subtype of gastric cancer (DGC) under Lauren's classification is more aggressive and usually occurs in younger patients than the intestinal subtype. The concept of personalized medicine is leading to the identification of multiple biomarkers in a large variety of cancers using different combinations of omics technologies. Proteomic changes including post-translational modifications are crucial in oncogenesis. We analyzed the phosphoproteome of DGC by using paired fresh frozen tumor and adjacent normal tissue from five patients diagnosed with DGC. We found proteins involved in the epithelial-to-mesenchymal transition (EMT), c-MYC pathway, and semaphorin pathways to be differentially phosphorylated in DGC tissues. We identified three kinases, namely, bromodomain adjacent to the zinc finger domain 1B (BAZ1B), WNK lysine-deficient protein kinase 1 (WNK1), and myosin light-chain kinase (MLCK) to be hyperphosphorylated, and one kinase, AP2-associated protein kinase 1 (AAK1), to be hypophosphorylated. LMNA hyperphosphorylation at serine 392 (S392) was demonstrated in DGC using immunohistochemistry. Importantly, we have detected heparin-binding growth factor (HDGF), heat shock protein 90 (HSP90), and FTH1 as potential therapeutic targets in DGC, as drugs targeting these proteins are currently under investigation in clinical trials. Although these new findings need to be replicated in larger study samples, they advance our understanding of signaling alterations in DGC, which could lead to potentially novel actionable targets in GC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a biomarkers | |
| 650 | 4 | |a cancer phosphoproteomics | |
| 650 | 4 | |a diffuse gastric cancer | |
| 650 | 4 | |a mass spectrometry | |
| 650 | 4 | |a personalized medicine | |
| 650 | 4 | |a precision medicine | |
| 650 | 7 | |a BAZ1B protein, human |2 NLM | |
| 650 | 7 | |a Bromodomain Containing Proteins |2 NLM | |
| 650 | 7 | |a Transcription Factors |2 NLM | |
| 700 | 1 | |a Parthasarathi, K T Shreya |e verfasserin |4 aut | |
| 700 | 1 | |a Bhat, Mohd Younis |e verfasserin |4 aut | |
| 700 | 1 | |a Gopal, Champaka |e verfasserin |4 aut | |
| 700 | 1 | |a Sharma, Jyoti |e verfasserin |4 aut | |
| 700 | 1 | |a Pandey, Akhilesh |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Omics : a journal of integrative biology |d 2002 |g 28(2024), 2 vom: 16. Feb., Seite 76-89 |w (DE-627)NLM117661910 |x 1557-8100 |7 nnns |
| 773 | 1 | 8 | |g volume:28 |g year:2024 |g number:2 |g day:16 |g month:02 |g pages:76-89 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1089/omi.2023.0173 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 28 |j 2024 |e 2 |b 16 |c 02 |h 76-89 | ||