Integrated proteomics and phosphoproteomics revealed druggable kinases in neoadjuvant chemotherapy resistant tongue...

Area of Science:

• Oncology
• Proteomics
• Molecular Biology

Background:

• Tongue squamous cell carcinoma is an aggressive oral cancer with high metastasis rates and poor prognosis.
• Many patients present with locally advanced, unresectable tumors, necessitating neoadjuvant therapy.
• Therapy resistance remains a significant clinical challenge in managing these patients.

Purpose of the Study:

• To investigate differential protein expression and phosphorylation in neoadjuvant chemotherapy-resistant tongue cancer.
• To identify molecular signatures associated with treatment resistance.
• To explore potential therapeutic targets for overcoming resistance.

Main Methods:

• Integrated proteomic and phosphoproteomic profiling of resistant and sensitive tongue cancer patient cohorts.
• Analysis of differential protein expression and phosphorylation in primary tumor tissues.
• Bioinformatic analysis including kinase signature identification and pathway enrichment.

Main Results:

• Observed differential and extensive phosphorylation of keratins (KRT10, KRT1) between resistant and sensitive groups.
• Identified a kinase signature involving MAPK1, AKT1, and MAPK3 associated with chemotherapy resistance.
• Pathway analysis revealed enrichment in Rho GTPase signaling and hyperphosphorylation of proteins involved in cell motility, invasion, and drug resistance.

Conclusions:

• Specific protein phosphorylation patterns, particularly of keratins, distinguish chemotherapy-resistant tongue cancer.
• A kinase signature including MAPK1, AKT1, and MAPK3 is implicated in neoadjuvant chemotherapy resistance.
• Targeting identified kinases presents a potential strategy for improving clinical management of resistant oral cancer.