Aberrant DNA replication is one of the driving forces behind oncogenesis. Furthermore, minichromosome maintenance complex component 3 (MCM3) serves an essential role in DNA replication. Therefore, in the present study, the diagnostic and prognostic value of MCM3 and its interacting proteins in hepatocellular carcinoma (HCC) were investigated. By utilizing The Cancer Genome Atlas (TCGA) database, global MCM3 mRNA levels were assessed in HCC and normal liver tissues. Its effects were further analyzed by reverse transcription-quantitative PCR (RT-qPCR), western blotting and immunohistochemistry in 78 paired HCC and adjacent tissues. Functional and pathway enrichment analyses were performed using the Search Tool for the Retrieval of Interacting Genes database. The expression levels of proteins that interact with MCM3 were also analyzed using the TCGA database and RT-qPCR. Finally, algorithms combining receiver operating characteristic (ROC) curves were constructed using binary logistic regression using the TCGA results. Increased MCM3 mRNA expression with high α-fetoprotein levels and advanced Edmondson-Steiner grade were found to be characteristic of HCC. Survival analysis revealed that high MCM3 expression was associated with poor outcomes in patients with HCC. In addition, MCM3 protein expression was associated with increased tumor invasion in HCC tissues. MCM3 and its interacting proteins were found to be primarily involved in DNA replication, cell cycle and a number of binding processes. Algorithms combining ROCs of MCM3 and its interacting proteins were found to have improved HCC diagnosis ability compared with MCM3 and other individual diagnostic markers. In conclusion, MCM3 appears to be a promising diagnostic biomarker for HCC. Additionally, the present study provides a basis for the multi-gene diagnosis of HCC using MCM3.
Traditional imaging examinations have difficulty in identifying benign and malignant changes in renal masses. This difficulty may be solved by ultrasound molecular imaging based on targeted nanobubbles, which could specifically enhance the ultrasound imaging of renal cell carcinomas (RCC) so as to discriminate benign and malignant renal masses. In this study, we aimed to prepare anti-G250 nanobody-functionalized targeted nanobubbles (anti-G250 NTNs) by coupling anti-G250 nanobodies to lipid nanobubbles and to verify their target specificity and binding ability to RCC cells that express G250 antigen and their capacity to enhance ultrasound imaging of RCC xenografts. Anti-G250 nanobodies were coupled to the lipid nanobubbles using the biotin-streptavidin bridge method. The average particle diameter of the prepared anti-G250 NTNs was 446 nm. Immunofluorescence confirmed that anti-G250 nanobodies were uniformly distributed on the surfaces of nanobubbles. In vitro experiments showed that the anti-G250 NTNs specifically bound to G250-positive 786-O cells and HeLa cells with affinities of 88.13% ± 4.37% and 71.8% ± 5.7%, respectively, and that they did not bind to G250-negative ACHN cells. The anti-G250 NTNs could significantly enhance the ultrasound imaging of xenograft tumors arising from 786-O cells and HeLa cells compared with blank nanobubbles, while the enhancement was not significant for xenograft tumors arising from ACHN cells. Immunofluorescence of tumor tissue slices confirmed that the anti-G250 NTNs could enter the tissue space through tumor blood vessels and bind to tumor cells specifically. In conclusion, anti-G250 nanobody-functionalized targeted nanobubbles could specifically bind to G250-positive RCC cells and enhance the ultrasound imaging of G250-positive RCC xenografts. This study has high-potential clinical application value for the diagnosis and differential diagnosis of renal tumors.
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