Phosphoproteomics Reveals Key Regulatory Kinases and Modulated Pathways Associated with Ovarian Cancer Tumors

BACKGROUND: Ovarian cancer (OC) is the seventh most common cancer worldwide for women. However, there are no sufficient diagnostic methods and few treatment options available due to poor understanding of its pathogenic mechanisms. METHODS: To comprehensively analyze the phosphoproteomic characterization for OC, we took advantage of a quantitative global phosphoproteomics method, titanium(IV) immobilized metal affinity chromatography (Ti(4+)-IMAC) coupled to nanoscale liquid chromatography and quadrupole time-of-flight tandem mass spectrometry (nanoLC/Q-TOF-MS/MS) on ovarian tissue samples obtained from five OC patients and five matched controls. RESULTS: A total of 722 phosphorylated sites corresponding to 534 proteins were significantly different (fold change ≥ 2, p < 0.01) between OC patients and the controls. Among them, 83 transcription factors mainly consisted of transcription cofactors, zf-C2H2, and chromatin remodeling factors and 29 kinases were included. Further functional analysis suggested significantly biological processes were highly enriched and involved in the pathogenesis of OC, especially fructose and mannose metabolism. Moreover, the regulatory roles of modulated pathways, including MAPK, ErbB, and GnRH signaling pathways were also identified as critical processes involved in OC. The results here highlighted key phosphorylated proteins, particularly kinases, and the corresponding cancer-related metabolic and signal pathways that played important roles in the development of OC. Additionally, the expression levels of two kinases, phosphorylated CDK (T14) and phosphorylated PRKCQ (S695), were validated by Western blot analysis in the other group of ovarian tissue samples. CONCLUSION: Altogether, our data not only provided novel insights into the potential biomarkers and therapy options for OC but also extended our knowledge on its pathophysiological mechanism.