RESUMEN
SPC24 is a crucial component of the mitotic checkpoint machinery in tumorigenesis. High levels of SPC24 have been found in various cancers, including breast cancer, lung cancer, liver cancer, osteosarcoma and thyroid cancer. However, to the best of our knowledge, the impact of SPC24 on prostate cancer (PCa) and other prostate diseases remains unclear. In the present study expression of global SPC24 messenger RNA (mRNA) was assessed in a subset of patients with PCa included in The Cancer Genome Atlas (TCGA) database. Increased levels of SPC24 expression were found in PCa patients >60 years old compared to patients <60 and increased SPC24 expression was also associated with higher levels of prostate specific antigen (P<0.05) and lymph node metastasis (P<0.05). Higher levels of SPC24 expression were associated with negative outcomes in PCa patients (P<0.05). Furthermore, in Chinese patients with prostatitis, benign prostatic hypertrophy (BPH) and PCa, SPC24 was expressed at significantly higher levels than that in adjacent/normal tissues, as assessed by reverse transcription-quantitative polymerase chain reaction, immunohistochemistry and western blotting. High expression of SPC24 was associated with high Gleason stages (IV and V; P<0.05). Further analysis, based on Gene Ontology and pathway functional enrichment analysis, suggested that nuclear division cycle 80 (NDC80), an SPC24 protein interaction partner, and mitotic spindle checkpoint serine/threonine-protein kinase BUB1 (BUB1), a core subunit of the spindle assembly checkpoint, may be associated with SPC24 in PCa development. Finally, using binary logistic regression, algorithms combining the receiver operating characteristic between SPC24 and BUB1 or NDC80 indicated that a combination of these markers may provide better PCa diagnosis ability than other PCa diagnosis markers. Taken together, these findings suggest that SPC24 may be a promising prostate disease biomarker.
RESUMEN
Minichromosome maintenance complex component 6 (MCM6) is involved in tumorigenesis of hepatocellular carcinoma (HCC). Because its effect on different populations remains unclear, this study investigated the impact of MCM6 on HCC in Southern Chinese Zhuang population. In addition to assessing the global mRNA levels of MCM6 based on The Cancer Genome Atlas database (TCGA) and The Gene Expression Omnibus database (GEO), associations between MCM6 mRNA levels and clinicopathological features were analyzed. High MCM6 levels were associated with high alpha-fetoprotein (AFP) (>20 ng/mL in serum) (P < 0.0001) and advanced clinical stage (III + IV) (P < 0.001). Higher MCM6 was associated with poorer outcomes (P < 0.01) in these databases. Furthermore, the mRNA and protein expression of MCM6 in the Guangxi Zhuang population was detected by quantitative polymerase chain reaction (qPCR), western blot, and immunohistochemistry (IHC). The results showed that MCM6 levels were up-regulated in the Zhuang population with HCC. Higher MCM6 protein levels were correlated with larger tumor size (>5 cm) (P = 0.038) and advanced clinical stage (III + IV) (p = 0.023). Bioinformatic enrichment analysis of MCM6 and its interacting proteins (CDT1,WEE1,TRIM28 and MKI67) suggested that in addition to being involved in the cell cycle process, these complexes could also be involved in protein binding, pre-replication complex assemble, and nucleus metabolism. Based on the protein-protein interaction (PPI) network with module screen, the interactions between MCM6 and its potential interacting proteins were further studied through protein docking with hot spot analysis. Additionally, the results of the algorithms combining the ROC of MCM6 and its interacting proteins showed that combination biomarker analysis has better HCC diagnosis ability than the single MCM6 test. The combination of MCM6 and TRIM28 was more suitable for the Guangxi Zhuang population. Overall, our study suggests that MCM6 plays an important role in the growth of HCC. MCM6 could be an optimal biomarker for diagnosing HCC and a potential molecular target for HCC therapy in the Zhuang population.