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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.
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BACKGROUND: This study was mainly to explore and study the potential application of lipoxygenases (ALOX) family genes in the diagnostic and prognostic values of colon adenocarcinoma (COAD). METHODS: Data sets related to the ALOX genes of COAD were obtained from The Cancer Genome Atlas and the University of California, Santa Cruz Xena browser. Then, the relevant biological information was downloaded from the public data platform. Finally, the bioinformatics technologies and clinical verification were employed to comprehensively analyze the potential values of ALOX genes. RESULTS: The Pearson correlation analysis indicated that there were correlations among ALOXE3, ALOX5, ALOX12, and ALOX12B. The diagnostic receiver operating characteristic (ROC) curves suggested that ALOXE3 and ALOX12 had significant diagnosis in COAD: ALOXE3; P<0.001, area under curve (AUC) 95%CI:=0.818 (0.773-0.862) and ALOX12; P<0.001, AUC 95%CI=0.774 (0.682-0.807). Besides, the verification study indicated that ALOX12 had a diagnostic value in COAD. Finally, our multivariate survival analysis and comprehensive prognosis of ALOX genes in COAD suggested that the ALOXE3 and ALOX12 were associated with COAD overall survival: ALOXE3; P=0.025, HR 95%CI=1.765 (1.074-2.901), ALOX12; P=0.046, HR 95%CI=1.680 (1.009-2.796), and the low expression of ALOXE3 and ALOX12 had a favorable prognosis of COAD (all P<0.05); on the contrary, the high regulation of them increased the risk of death. CONCLUSION: In our study, we observed that the mRNA expressions of ALOX genes were associated with the diagnosis and prognosis of COAD. The results of the diagnostic analysis suggested that ALOX12 might have a diagnosis value in COAD. Besides, our comprehensive prognosis analysis indicated that ALOXE3 combined ALOX12 might serve as potential prognosis biomarkers for COAD.
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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.
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In the present study, the significance of GABAA genes in colon adenocarcinoma (COAD) were investigated from the view of diagnosis and prognosis. All data were achieved from The Cancer Genome Atlas. Overall survival was analyzed by the Kaplan-Meier analyses and Cox regression model and the hazard ratios and 95% confidence interval were calculated for computation. The Database for Annotation, Visualization and Integrated Discovery, and the Biological Networks Gene Ontology (BiNGO) softwares were applied to assess the biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for pathway analysis to predict the biological function of GABAA genes. The associated Gene Ontology and KEGG pathways were conducted by Gene Set Enrichment Analysis (GSEA). From receiver operating characteristics curves analysis, it was found that the expression of GABR, γ-aminobutyric acid type A receptor GABRA2, GABRA3, GABRB2, GABRB3, GABRG2, GABRG3, GABRD, GABRE were correlated with COAD occurrence [P<0.0001, area under the curve (AUC)>0.7]. The low expression of the GABRB1, GABRD, GABRP and GABRQ in genes after tumor staging adjustment were positively correlated with the overall survival rate [P=0.049, hazard ratio (HR)=1.517, 95% confidence interval (CI)=1.001-2.297; P=0.006, HR=1.807, 95% CI=1.180-2.765; P=0.005, HR=1.833, 95% CI=1.196-2.810; P=0.034, HR=1.578, 95% CI=1.036-2.405). GSEA showed enrichment of cell matrix adhesion, integrin binding, angiogenesis, endothelial growth factor and endothelial migration regulation in patients with COAD with GABRD overexpression. GABRB1, GABRD, GABRP and GABRQ were associated with the prognostic factors of COAD. The expression levels of GABRA2, GABRA3, GABRB2, GABRB3, GABRG2, GABRD and GABRE may allow differentiation between tumor tissues and adjacent normal tissues.
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BACKGROUND: Radiation sensitive 52 (RAD52) is an important protein that mediates DNA repair in tumors. However, little is known about the impact of RAD52 on hepatocellular carcinoma (HCC). We investigated the expression of RAD52 and its values in HCC. Some proteins that might be coordinated with RAD52 in HCC were also analyzed. METHODS: Global RAD52 mRNA levels in HCC were assessed using The Cancer Genome Atlas (TCGA) database. RAD52 expression was analyzed in 70 HCC tissues and adjacent tissues by quantitative real-time PCR (qRT-PCR), Western blotting and immunohistochemistry. The effect of over-expressed RAD52 in Huh7 HCC cells was investigated. The String database was then used to perform enrichment and functional analysis of RAD52 and its interactome. Cytoscape software was used to create a protein-protein interaction network. Molecular interaction studies with RAD52 and its interactome were performed using the molecular docking tools in Hex8.0.0. Finally, these DNA repair proteins, which interact with RAD52, were also analyzed using the TCGA dataset and were detected by qRT-PCR. Based on the TCGA database, algorithms combining ROC between RAD52 and RAD52 interactors were used to diagnose HCC by binary logistic regression. RESULTS: In TCGA, upregulated RAD52 related to gender was obtained in HCC. The area under the receiver operating characteristic curve (AUC) of RAD52 was 0.704. The results of overall survival (OS) and recurrence-free survival (RFS) indicated no difference in the prognosis between patients with high and low RAD52 gene expression. We validated that RAD52 expression was increased at the mRNA and protein levels in Chinese HCC tissues compared with adjacent tissues. Higher RAD52 was associated with older age, without correlation with other clinicopathological factors. In vitro, over-expressed RAD52 significantly promoted the proliferation and migration of Huh7 cells. Furthermore, RAD52 interactors (radiation sensitive 51, RAD51; X-ray repair cross complementing 6, XRCC6; Cofilin, CFL1) were also increased in HCC and participated in some biological processes with RAD52. Protein structure analysis showed that RAD52-RAD51 had the firmest binding structure with the lowest E-total energy (- 1120.5 kcal/mol) among the RAD52-RAD51, RAD52-CFL1, and RAD52-XRCC6 complexes. An algorithm combining ROC between RAD52 and its interactome indicated a greater specificity and sensitivity for HCC screening. CONCLUSIONS: Overall, our study suggested that RAD52 plays a vital role in HCC pathogenesis and serves as a potential molecular target for HCC diagnosis and treatment. This study's findings regarding the multigene prediction and diagnosis of HCC are valuable.
