Comprehensive clinicopathological significance and putative transcriptional mechanisms of Forkhead box M1 factor in hepatocellular carcinoma.

BACKGROUND: The Forkhead box M1 factor (FOXM1) is a crucial activator for cancer cell proliferation. While FOXM1 has been shown to promote hepatocellular carcinoma (HCC) progression, its transcriptional mechanisms remain incompletely understood. METHODS: We performed an in-house tissue microarray on 313 HCC and 37 non-HCC tissue samples, followed by immunohistochemical staining. Gene chips and high throughput sequencing data were used to assess FOXM1 expression and prognosis. To identify candidate targets of FOXM1, we comprehensively reanalyzed 41 chromatin immunoprecipitation followed by sequencing (ChIP-seq) data sets. We predicted FOXM1 transcriptional targets in HCC by intersecting candidate FOXM1 targets with HCC overexpressed genes and FOXM1 correlation genes. Enrichment analysis was employed to address the potential mechanisms of FOXM1 underlying HCC. Finally, single-cell RNA sequencing analysis was performed to confirm the transcriptional activity of FOXM1 on its predicted targets. RESULTS: This study, based on 4235 HCC tissue samples and 3461 non-HCC tissue samples, confirmed the upregulation of FOXM1 in HCC at mRNA and protein levels (standardized mean difference = 1.70 [1.42, 1.98]), making it the largest multi-centered study to do so. Among HCC patients, FOXM1 was increased in Asian and advanced subgroups, and high expression of FOXM1 had a strong ability to differentiate HCC tissue from non-HCC tissue (area under the curve = 0.94, sensitivity = 88.72%, specificity = 87.24%). FOXM1 was also shown to be an independent exposure risk factor for HCC, with a pooled hazard ratio of 2.00 [1.77, 2.26]. The predicted transcriptional targets of FOXM1 in HCC were predominantly enriched in nuclear division, chromosomal region, and catalytic activity acting on DNA. A gene cluster encoding nine transcriptional factors was predicted to be positively regulated by FOXM1, promoting the cell cycle signaling pathway in HCC. Finally, the transcriptional activity of FOXM1 and its targets was supported by single-cell analysis of HCC cells. CONCLUSIONS: This study not only confirmed the upregulation of FOXM1 in HCC but also identified it as an independent risk factor. Moreover, our findings enriched our understanding of the complex transcriptional mechanisms underlying HCC pathogenesis, with FOXM1 potentially promoting HCC progression by activating other transcription factors within the cell cycle pathway.

[Retracted] Protective effects of baicalin on rabbit articular chondrocytes in vitro.

[This retracts the article DOI: 10.3892/etm.2017.4116.].

CCNB1 is involved in bladder cancer pathogenesis and silencing CCNB1 decelerates tumor growth and improves prognosis of bladder cancer.

In search of an effective therapeutic target for bladder urothelial carcinoma (BLCA), the present study aimed to investigate the expression of cyclin B1 (CCNB1) and its putative mechanism in BLCA. BLCA sequencing data from Gene Expression Omnibus and The Cancer Genome Atlas were used to analyze expression of CCNB1 mRNA and high CCNB1 expression had a poorer prognosis compared with those with low expression. Immunohistochemistry (IHC) samples collected from the Human Protein Atlas database were analyzed for CCNB1 protein expression. Short hairpin (sh) CCNB1-transfected BLCA T24 and 5637 cells were used to investigate the effects of CCNB1 and inhibit the proliferation, migration and invasion of BLCA cells, affect the cell cycle distribution and promote apoptosis of 5637 cells. A sh-CCNB1 BLCA chicken embryo chorioallantoic membrane (CAM) transplantation model was established to observe the impacts of sh-CCNB1 on the tumorigenesis of BLCA in vivo. Analysis of sequencing data showed that CCNB1 mRNA was significantly elevated in tumor and BLCA compared with normal tissues [standardized mean difference (SMD)=1.21; 95% CI: 0.26-2.15; I²=95.9%]. IHC indicated that CCNB1 protein was localized in the nucleus and cytoplasm and was significantly increased in BLCA tumor tissues. The in vitro tests demonstrated that proliferation of T24 and 5637 cells transfected with sh-CCNB1 was significantly inhibited and cell migration and invasion ability were significantly decreased. sh-CCNB1 decreased the percentage of T24 cells in G0/G1, 5637 cells in the G0/G1 phase and S phase and increased percentage of 5637 cells in the G2/M phase and increased early apoptosis of 5637 cells. The in vivo experiments demonstrated that the mass of transplanted tumors was significantly decreased compared with the control group following silencing of CCNB1. The present results suggested that CCNB1 was involve in the development and prognosis of BLCA and silencing of CCNB1 may be a promising targeted therapy for BLCA.

Clinical Implication of E2F Transcription Factor 1 in Hepatocellular Carcinoma Tissues.

Background: To date, the clinical management of advanced hepatocellular carcinoma (HCC) patients remains challenging and the mechanisms of E2F transcription factor 1 (E2F1) underlying HCC are obscure. Materials and Methods: Our study integrated datasets mined from several public databases to comprehensively understand the deregulated expression status of E2F1. Tissue microarrays and immunohistochemistry staining was used to validate E2F1 expression level. The prognostic value of E2F1 was assessed. In-depth subgroup analyses were implemented to compare the differentially expressed levels of E2F1 in HCC patients with various tumor stages. Functional enrichments were used to address the predominant targets of E2F1 and shedding light on their potential roles in HCC. Results: We confirmed the elevated expression of E2F1 in HCC. Subgroup analyses indicated that elevated E2F1 level was independent of various stages in HCC. E2F1 possessed moderate discriminatory capability in differentiating HCC patients from non-HCC controls. Elevated E2F1 correlated with Asian race, tumor classification, neoplasm histologic grade, eastern cancer oncology group, and plasma AFP levels. Furthermore, high E2F1 correlated with poor survival condition and pooled HR signified E2F1 as a risk factor for HCC. Enrichment analysis of differentially expressed genes, coexpressed genes, and putative targets of E2F1 emphasized the importance of cell cycle pathway, where CCNE1 and CCNA2 served as hub genes. Conclusions: We confirmed the upregulation of E2F1 and explored the prognostic value of E2F1 in HCC patients. Two putative targeted genes (CCNE1 and CCNA2) of E2F1 were identified for their potential roles in regulating cell cycle and promote antiapoptotic activity in HCC patients.

Comparing the accuracy of shear wave elastography and strain elastography in the diagnosis of breast tumors: A systematic review and meta-analysis.

BACKGROUND: Shear wave elastography (SWE) and strain elastography (SE) are 2 new ultrasonic technologies which have developed rapidly in recent years. Elastography transforms the elastic information of tissue into optical information for display, thus more intuitive display of tissue elasticity. Conflicting results have been obtained in different scholars' studies on the accuracy comparison of the 2 elastography technologies in the diagnosis of breast tumors. This meta-analysis aims to compare the accuracy of the 2 elastography technologies in the diagnosis of breast tumors, and provide a reference for clinical decision making. METHODS: We have searched Chinese and English literatures on the accuracy of SWE and SE in the diagnosis of breast tumors from PubMed, Web of Science, China national knowledge infrastructure and Wanfang databases, and the time was up to December30, 2020. Two literature reviewers screened the literatures according to the screening criteria, and Quality Assessment of Diagnostic Accuracy Study tool was used to evaluate the quality of included literatures. Meta Disc1.4 and Stata14.0 softwares were used to perform heterogeneity test, sensitivity analysis and publication bias test. RESULTS: Ten literatures included 1599 patients and 1709 breast lesions. The final results in the SWE as follow: The pooled sensitivity was 0.852 (95% confidence interval [CI] [0.826-0.874]), the pooled specificity (Spe) was 0.799 (95% CI [0.776-0.820]), the pooled positive likelihood ratio was 4.758 (95% CI [3.443-6.576]), the pooled negative likelihood ratio was 0.192 (95% CI [0.147-0.250]), the pooled diagnostic odds ratio was 29.071 (95% CI [16.967-49.811]), and the area under the summary receiver operating characteristic curve was 0.9159. The final results in the SE as follow: The pooled sensitivity was 0.843 (95% CI [0.817-0.866]), the pooled Spe was 0.766 (95% CI [0.743-0.789]), the pooled positive likelihood ratio was 4.387 (95% CI [3.088-6.233]), the pooled negative likelihood ratio was 0.216 (95% CI [0.179-0.261]), the pooled diagnostic odds ratio was 22.610 (95% CI [15.622-32.724]), and the area under the summary receiver operating characteristic curve was 0.8987. CONCLUSION: The sensitivity and Spe of SWE were higher than those of SE, suggesting that SWE may have a higher accuracy in the diagnosis of breast tumors. REGISTER NAME: PROSPERO. Registration number: CRD42021251110.

An EPR-Independent extravasation Strategy: Deformable leukocytes as vehicles for improved solid tumor therapy.

Effective delivery of therapeutic modality throughout the tumorous nidus plays a crucial role in successful solid tumor treatment. However, conventional nanomedicines based on enhanced permeability and retention (EPR) effect have yielded limited delivery/therapeutic efficiency, due mainly to the heterogeneity of the solid tumor. Leukocytes, which could intrinsically migrate across the vessel wall and crawl through tissue interstitium in a self-deformable manner, have currently emerged as an alternative drug delivery vehicle. In this review, we start with the intrinsic properties of leukocytes (e.g., extravasation and crawling inside tumor), focusing on unveiling the conceptual rationality of leveraging leukocytes as EPR-independent delivery vehicles. Then we discussed various cargoes-loading/unloading strategies for leukocyte-based vehicles as well as their promising applications. This review aims to serve as an up-to-date compilation, which might provide inspiration for scientists in the field of drug delivery.

Comparing the accuracy between shear wave elastography and strain elastography in the diagnosis of breast tumors: Systematic review and meta-analysis.

BACKGROUND: Shear wave elastography and strain elastography are two new ultrasonic techniques developed rapidly in recent years. Changes in tissue elasticity occur after normal tissue changes. Elastography technique transforms the elastic information of tissue into optical information for display. Thus more intuitive display of tissue elasticity. Due to the differences in principles and related imaging parameters between the two elastic imaging methods, and the acquisition and interpretation of image data in strain elastic imaging method largely depends on the experience of inspectors, and due to the significant differences between the techniques of inspectors, As a result, conflicting results have been obtained in different scholars' studies on the accuracy comparison of the two elastography techniques in the diagnosis of breast tumors. This meta-analysis aims to compare the accuracy of the two elastography methods in the diagnosis of breast tumors, so as to provide more accurate diagnostic means for patients with breast tumors. The final results will show which elastography method is more accurate in the diagnosis of breast tumors, reduce unnecessary biopsies and provide a reference for clinical decision making. METHODS: We will examine published and unpublished randomized controlled trials, observational studies and abstracts without publication type or language restrictions, and search relevant literatures in PubMed, Web of Science, Wanfang Database, CNQI and other databases until December 30, 2020. The authors will independently search relevant literature records, scan titles and abstracts, full text, collect data and assess the risk of bias. Data will be analyzed by using Meta Disc1.4 software and Stata14.0 software. Heterogeneity tests and combined sensitivity, specificity, positive and negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve will be performed by using Meta Disc1.4 software. Stata14.0 software will be used for sensitivity analysis and publication bias test. RESULTS: The results of this systematic review will demonstrate the accuracy of the two elastography methods in the diagnosis of breast tumors. DISCUSSION: The results will provide useful evidence for the comparison of the diagnostic accuracy of shear wave elastography and strain elastography in breast tumors. OTHER: This study was not funded. Register name: PROSPERO. Registration number: CRD42021251110.

Erratum: Effect of CELSR3 on the Cell Cycle and Apoptosis of Hepatocellular Carcinoma Cells: Erratum.

[This corrects the article DOI: 10.7150/jca.39328.].

Erratum: Baicalin promotes the viability of Schwann cells in vitro by regulating neurotrophic factors.

[This corrects the article DOI: 10.3892/etm.2017.4524.].

Clinical Significance of Integrin Subunit Beta 4 in Head and Neck Squamous Cell Carcinoma.

Background: The expression level and clinical significance of integrin subunit beta 4 (ITGB4) in head and neck squamous cell carcinoma (HNSCC) remain unclear. Materials and Methods: Expression of ITGB4 in HNSCC tissues was evaluated by calculating standard mean differences (SMDs) based on gene chips, RNA-seq, and immunohistochemistry data (n = 2330) from multiple sources. Receiver operating characteristic (ROC) curves were used to detect the ability of ITGB4 to distinguish HNSCC from non-HNSCC samples. The relationship between the expression level of ITGB4 and clinical parameters was evaluated by calculating SMDs. Results: Identical results of mRNA and protein levels indicated remarkable up-expression of ITGB4 in HNSCC tissues. Further ROC curves showed that ITGB4 could distinguish HNSCC from non-HNSCC samples. Genetic alteration analysis of ITGB4 in HNSCC indicated that overexpression of ITGB4 in HNSCC was likely not owing to genetic alteration of ITGB4. Moreover, ITGB4 overexpression level may be correlated with clinical T stage. Conclusion: ITGB4 likely plays an essential role in HNSCC occurrence based on our study and its potential diagnostic value is worthy of further exploration in the future.

[Corrigendum] Murine and Chinese cobra venom­derived nerve growth factor stimulate chondrogenic differentiation of BMSCs in vitro: A comparative study.

Subsequently to the publication of this paper, an interested reader drew to the authors' attention that Figs. 2 and 3, showing the results from experiments designed to assess the viability of bone­derived mesenchymal stem cells culture with or without nerve growth factors (NGFs) via fluorescein diacetate/propidium iodide or H&E staining respectively, contained apparently duplicated data panels within the figures. After having examined their original data, the authors have realized that these figures were inadvertently assembled incorrectly, and that there were also misassembled data panels in Fig. 6, which showed the secretion of types I and II collagens in bone­derived mesenchymal stem cells with or without NGFs. The corrected versions of Figs. 2, 3 and 6 are shown below and on the next page. Note that these errors did not significantly affect the results or the conclusions reported in this paper, and all the authors agree to this Corrigendum. Furthermore, the authors apologize to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 10.3892/mmr.2018.9307].

(4,5,8)-Connected Cationic Coordination Polymer Material as Explosive Chemosensor Based on the in Situ Generated AIE Tetrazolyl-Tetraphenylethylene Derivative.

A multidentate tetrazole molecule based on a TPE core, tetrakis[4-(1H-tetrazol-5-yl)phenyl]ethylene (H4ttpe) with combined advantages of two functional groups, was synthesized by cycloaddition reaction of the corresponding organic benzonitrile derivative and azide salt. Coordination self-assembly of the in situ formed aggregation-induced emission polytetrazole luminogen with cadmium(II) ion produces an unprecedented tetrazolyl-TPE-based microporous cationic metal-organic framework (MOF) with an unusual (4,5,8T14)-connected net of {[Cd4(H4ttpe)2Cl5]·(N3)3}, in which the H4ttpe serves as the first undeprotonated tetrazole ligand of octa-coordinating bridging mode. We investigate, for the first time, the utilization of the luminescent MOF containing a TPE core decorated with tetrazolyl terminals for explosive detection based on the change in fluorescence intensity, which shows high selectivity and efficiency in fluorescence quenching toward TNP detection in water solution.

Mutational Analysis of EXT1in a Chinese Family Affected by Hereditary Multiple Osteochondroma.

OBJECTIVES: To discuss the mutational features and their relationships with disease in a family with hereditary multiple osteochondroma (HMO) from Guangxi Province (GXBB-1 family), China. METHODS: Genomic DNA and total mRNA were extracted from peripheral blood cells of GXBB-1 family members. Whole elements of the EXT1gene and its transcript, including exons, introns, exon-intron boundaries, and coding sequence (CDS) clones, were amplified and sequenced. Allele-specific PCR was used to confirm the position and type of mutation. RESULTS: All patients from the GXBB-1 family harbored the cosegregating heterozygous c.1056+1G>A mutation located in EXT1at an exon-intron boundary. Another three single-nucleotide polymorphisms (SNPs) were also detected in the patients, including IVS2+1G>A in intron 2, c.1844 T>C [p.Pro (CCT) 614Pro (CCC)] in exon 3, and c.2534G>A [p.Glu (GAG) 844Glu (GAA)] in exon 9. The latter two SNPs were synonymous variations. CONCLUSIONS: The heterozygous c.1056+1G>A mutation cosegregated with the phenotype, indicating that it is a pathogenic mutation in the GXBB-1 family. This mutation is reported for the first time in Chinese HMO patients. IVS2+1G>A and c.2534G>A have no relationship with the occurrence of disease. However, c.1844 T>C and c.1056+1G>A are linked, and their interaction needs to be further studied. c.1844T>C is a new SNP that has not been reported internationally.

Atomic Welded Dual-Wall Hollow Nanospheres for Three-in-One Hybrid Storage Mechanism of Alkali Metal Ion Batteries.

The rational design of hierarchical hollow nanomaterials is of critical significance in energy storage materials. Herein, dual-wall hollow nanospheres (DWHNS) Sn/MoS2@C are constructed by in situ confined growth and interface engineering. The inner hollow spheres of Sn/MoS2 are formed by atomic soldering MoS2 nanosheets with liquid Sn at high temperature. The formation mechanism of the hierarchical structure is explored by the morphology evolutions at different temperatures. The DWHNS Sn/MoS2@C manifest abundant inner space and high specific surface area, which provides more support sites for Li+/Na+/K+ storage and alleviates the volume effect of tin-based electrode materials to a certain extent. The composite material manifests an outstanding specific capacity and satisfactory reversibility of lithium ion batteries (∼931 mAh g-1 at 1 A g-1 after 500 cycles), sodium ion batteries (∼432 mAh g-1 at 1 A g-1 after 400 cycles), and potassium ion batteries (∼226 mAh g-1 at 1 A g-1 after 300 cycles). Additionally, the morphology evolution and mechanism analysis of DWHNS Sn/MoS2@C in alkali metal ion batteries are verified by ex situ measurement, which confirms the three-in-one hybrid storage mechanism, i.e., intercalation reaction of carbon shells, conversion reaction of MoS2, and alloying reaction of tin.

The dynamic interplay between intramolecular and intermolecular interactions in mononuclear manganese(III) SCO complexes.

The effect of counter anions on thermally induced manganese(iii)-based SCO within the [Mn(5-F-sal-N-1,5,8,12)]Y family has been investigated. All the complexes are crystallized without any lattice solvents. Crystal packing and intermolecular forces influence the spin-state stabilization and spin-transition profiles. Magnetic measurements indicate that salts with octahedral anions, [Mn(5-F-sal-N-1,5,8,12)]PF6 (1), [Mn(5-F-sal-N-1,5,8,12)]AsF6 (2) and [Mn(5-F-sal-N-1,5,8,12)]SbF6 (3), show HS electronic configurations between 2 and 300 K, and there exist π-π stackings between the phenyl groups from the neighboring [Mn(5-F-sal-N-1,5,8,12)]+ cations. As for the tetrahedral anions, complex [Mn(5-F-sal-N-1,5,8,12)]BF4 (4) exhibits a gradual and incomplete spin conversion. Complex [Mn(5-F-sal-N-1,5,8,12)] ClO4 (5) shows a nearly complete SCO with T1/2 = 100 K. The remaining salts with spherical anions form Nam-HX (X = Cl, Br, I) hydrogen bonds between Mn(iii) cations and counterions. Complexes [Mn(5-F-sal-N-1,5,8,12)]Cl (6) and [Mn(5-F-sal-N-1,5,8,12)] Cl0.28Br0.72 (7) feature gradual SCO behaviors with T1/2 = 220 K and 235 K, respectively. Complex [Mn(5-F-sal-N-1,5,8,12)]I (8) exhibits a more gradual spin conversion and is far from a complete HS state with a χMT value of 1.89 cm3 mol-1 K at 400 K.

Erratum: Protective effects of baicalin on rabbit articular chondrocytes in vitro.

[This corrects the article DOI: 10.3892/etm.2017.4116.].

A Bacteria-Inspired Morphology Genetic Biomedical Material: Self-Propelled Artificial Microbots for Metastatic Triple Negative Breast Cancer Treatment.

Morphology genetic biomedical materials (MGBMs), referring to fabricating materials by learning from the genetic morphologies and strategies of natural species, hold great potential for biomedical applications. Inspired by the cargo-carrying-bacterial therapy (microbots) for cancer treatment, a MGBM (artificial microbots, AMBs) was constructed. Rather than the inherent bacterial properties (cancerous chemotaxis, tumor invasion, cytotoxicity), AMBs also possessed ingenious nitric oxide (NO) generation strategy. Mimicking the bacterial construction, the hyaluronic acid (HA) polysaccharide was induced as a coating capsule of AMBs to achieve long circulation in blood and specific tissue preference (tumor tropism). Covered under the capsule-like polysaccharide was the combinatorial agent, the self-assembly constructed by the amphiphilic dendrons with abundant l-arginine residues peripherally (as endogenous NO donor) and hydrophobic chemotherapeutic drugs at the core stacking on the surface of SWNTs (the photothermal agent) for a robust chemo-photothermal therapy (chemo-PTT) and the elicited immune therapy. Subsequently, the classic inducible nitric oxide synthase (iNOS) pathway aroused by immune response was revolutionarily utilized to oxidize the l-arginine substrates for NO production, the process for which could also be promoted by the high reactive oxygen species level generated by chemo-PTT. The NO generated by AMBs was intended to regulate vasodilation and cause a dramatic invasion (as the microbots) to disperse the therapeutic agents throughout the solid tumor for a much more enhanced curative effect, which we defined as "self-propulsion". The self-propelled AMBs exhibiting impressive primary tumor ablation, as well as the distant metastasis regression to conquer the metastatic triple negative breast cancer, provided pioneering potential therapeutic opportunities, and enlightened broad prospects in biomedical application.

A tumor-activatable peptide supramolecular nanoplatform for the delivery of dual-gene targeted siRNAs for drug-resistant cancer treatment.

Combinatorial short interference RNA (siRNA) technology for the silencing of multiple genes is expected to provide an effective therapeutic approach for cancer with complex genetic mutation and dysregulation. Herein we present a tumor-activatable supramolecular nanoplatform for the delivery of siRNAs to target telomerase and telomeres for paclitaxel-resistant non-small-cell lung cancer (A549/PTX) treatment. Two different sequences of siRNA are incorporated in a single nanoparticle, which is obtained by self-assembly from a peptide dendrimer. The siRNA stability is improved by the nanoparticle in the presence of serum compared to free siRNA, and these siRNAs are protected from RNA enzyme degradation. In the tumor extracellular acid environment, the PEG corona of the nanoparticle is removed to promote the internalization of siRNAs into tumor cells. The disulfide linkages between the nanoparticle and siRNAs are cleared in the reductive environment of the tumor cells, and the siRNAs are released in the cytoplasm. In vitro experiments show that the gene expression of hTERT and TRF2 at the mRNA and protein levels of A549/PTX tumor cells is down-regulated, which results in cooperative restraining proliferation and invasion of A549/PTX tumor cells. For the tumor cell-targeting function of the MUC1 aptamer and the EPR effect, sufficient tumor accumulation of nanoparticles was observed. Meanwhile, a shift of negative surface charge of nanoparticles to positive charge in the tumor extracellular microenvironment enhances deep penetration of siRNA-incorporating nanoparticles into tumor tissues. In vivo animal studies support that successful down-regulation of hTERT and TRF2 gene expression achieves effective inhibition of the growth and neovascularization of drug-resistant tumor cells. This work has provided a new avenue for drug-resistant cancer treatment by designing and synthesizing a tumor-activatable nanoplatform to achieve the delivery of dual-gene targeted combinatorial siRNAs.

Expression of Cell Division Cycle Protein 45 in Tissue Microarrays and the CDC45 Gene by Bioinformatics Analysis in Human Hepatocellular Carcinoma and Patient Outcomes.

BACKGROUND Hepatocellular carcinoma (HCC) causes a heavy disease burden worldwide. Cell division cycle 45 (Cdc45) and its encoding gene (CDC45) have been studied for a long time, but their expression patterns and roles in liver carcinogenesis and advanced HCC deterioration are still incompletely understood. This study integrated tissue microarray and bioinformatics analyses to explore the expression and clinical value of CDC45 and Cdc45 in HCC. MATERIAL AND METHODS In HCC, the expression and relationships with clinic-pathological parameters of CDC45 and Cdc45 were investigated by integrating the RNA-sequencing data, downloaded from The Cancer Genome Atlas and Oncomine databases, and tissue microarray with immunohistochemistry staining. Co-expressed genes and genetic alterations of CDC45 separately obtained from Oncomine and cBioPortal databases were identified to shed light on the potential mechanisms of CDC45 in HCC. RESULTS CDC45 and Cdc45 were both overexpressed in HCC tissues, and the CDC45 level progressively increased from stage I to III. The survival outcomes of the group with high CDC45 expression were significantly worse compared with the group with low expression. Amplification and deep deletion were 2 major significant alteration types in HCC patients, and the outcomes were worse in patients with altered versus unaltered CDC45. NUDT1, E2F1, CCNE2, MCM5, and CENPM were identified as the most significantly co-expressed genes. CONCLUSIONS CDC45 and Cdc45 were both upregulated in HCC, and increased expression levels and genetic alternations of CDC45 were correlated with worse prognosis in HCC patients. CDC45 may promote HCC by co-expressing with NUDT1, E2F1, CCNE2, MCM5, and CENPM.