Proteomic Analysis and NIR-II Imaging of MCM2 Protein in Hepatocellular Carcinoma

Targeted therapy of hepatocellular
carcinoma (HCC) is essential
for improved therapies. Therefore, identification of key targets specifically
to HCC is an urgent requirement. Herein, an iTRAQ quantitative proteomic
approach was employed to identify differentially expressed proteins
in HCC tumor tissues. Of the upregulated tumor-related proteins, minichromosome
maintenance 2 (MCM2), a DNA replication licensing factor, was one
of the most significantly altered proteins, and its overexpression
was confirmed using tissue microarray. Clinicopathological analysis
of multiple cohorts of HCC patients indicated that overexpression
of MCM2 was validated in 89.8% tumor tissues and strongly correlated
with clinical stage. Furthermore, siRNA-mediated repression of MCM2
expression resulted in significant suppression of the HepG2 cell cycle
and proliferation through the cyclin D-dependent kinases (CDKs) 2/7
pathway. Finally, the first small molecule-based MCM2-targeted NIR-II
probe CH1055-MCM2 was concisely generated and subsequently
evaluated in mice bearing HepG2 xenografts. The excellent imaging
properties such as good tumor uptake and high tumor contrast and specificity
were achieved in the small animal models. This analytical strategy
can determine novel accessible targets of HCC useful for imaging and
therapy.