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.

Laryngeal Squamous Cell Carcinoma: Potential Molecular Mechanism and Prognostic Signature Based on Immune-Related Genes.

BACKGROUND Immune-related genes (IRGs) are closely related to the incidence and progression of tumors, potentially indicating that IRGs play an important role in laryngeal squamous cell carcinoma (LSCC). MATERIAL AND METHODS An RNA sequencing dataset containing 123 samples was collected from The Cancer Genome Atlas. Based on immune-related differentially expressed genes (IRDEGs), a potential molecular mechanism of LSCC was explored through analysis of information in the Gene Ontology (GO) resource and the Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interactions (PPIs). A regulatory network of transcriptional regulators and IRDEGs was constructed to explore the underlying molecular mechanism of LSCC at the upstream level. Candidates from IRDEGs for signature were screened via univariate Cox analysis and using the least absolute shrinkage and selection operator (LASSO) technique. The IRDEG signature of LSCC was constructed by using a multivariate Cox proportional hazards model. RESULTS GO and KEGG analysis showed that IRDEGs may participate in the progression of LSCC through immune-related reactions. PPI analysis demonstrated that, among the IRDEGs in LSCC, the Kininogen 1; C-X-X motif chemokine ligand 10; elastase, neutrophil expressed; and LYZ genes are hub genes in the development of LSCC. At the upstream level, SPI1, SP140, signal transducer and activator of transcription 4, zinc finger E-box binding homeobox, and Ikaros family zinc finger 2 are the hub transcriptional regulators of IRDEGs. The risk score based on the IRDEG signature was able to distinguish prognosis in patients with LSCC and represents an independent prognostic risk factor for LSCC. CONCLUSIONS From the perspective of IRGs, we first constructed an IRDEG signature related to the prognosis of LSCC, which can be used as a novel marker to predict prognosis in patients with LSCC.

Small Nucleolar RNAs (snoRNAs)-Based Risk Score Classifier Predicts Overall Survival in Bladder Carcinoma.

BACKGROUND Bladder carcinoma (BLCA) is a leading cause of cancer-related deaths worldwide. The aim of this work was to develop an accurate stratification in predicting the prognosis and directing the treatment of BLCA patients based on small nucleolar RNAs (snoRNAs). MATERIAL AND METHODS Expression profiles of snoRNAs were downloaded from the SNORic database. The expression profiles and clinical outcomes of BLCA patients were analyzed. Survival-associated snoRNAs were identified and used to develop a novel risk score classifier. Genes in the whole genome that were significantly correlated with the included prognostic snoRNAs were used for functional enrichment analysis. RESULTS The results showed that age, American Joint Committee on Cancer (AJCC) stage, and tumor status were significantly correlated with overall survival (OS) of BLCA patients. We selected 12 survival-associated snoRNAs to build a prognostic signature. Patients were separated into high- and low-risk groups based on the median value of the risk score. Patients in the high-risk group and low-risk group have distinct clinical outcomes. The AJCC TNM stage showed moderate utility as a prognostic indicator for clinical outcome prediction. Then, clinical parameters and risk scores were entered in multivariate Cox analysis. Notably, the prognostic signature remained an independent significant prognostic risk factor. The pathway analysis suggested that these genes were enriched in several types of cancer and "Focal adhesion" pathways. CONCLUSIONS The prognostic signature defined by expression profiles of 12 survival-associated snoRNAs appears to be an excellent predictor of the clinical outcome of BLCA patients.

Identification of an Immune Score-Based Gene Panel with Prognostic Power for Oral Squamous Cell Carcinoma.

BACKGROUND Oral squamous cell carcinoma (OSCC) is the sixth most prevalent cancer worldwide, with low 5-year survival rate. To identify novel prognostic markers for OSCC and determine the immune and stromal landscape of OSCC, a risk signature for OSCC patients was constructed in this study. MATERIAL AND METHODS Immune and stromal scores for OSCC samples from the Genomic Data Commons Data Portal were computed to delineate the tumor microenvironment landscape of oral cancer based on the Estimation of STromal and Immune cells in MAlignant Tumours using Expression data algorithm. An immune score-based risk signature was constructed by combining random forest and support vector machine methods. Correlation analysis of risk signature gene expression and immune cell infiltration was conducted, and the distinguishing power of individual signature genes was evaluated by analyzing receiver operating characteristics (ROC) curves. Differentially enriched pathways between high and low risk groups were investigated via gene set variation analysis. ROC curves were plotted for signature genes to examine their ability to distinguish the recurrence and survival status of OSCC patients from GSE84846. RESULTS An immune score-related risk signature composed of ARMH1, F2RL2, AC004687.1, COL6A5, AC008750.1, RAB19, CRLF2, GRIP2, and FAM162B performed well in the prognostic stratification of OSCC patients and could effectively distinguish their survival status. Lists of pathways, including cytokine-cytokine receptor interaction and cell adhesion molecules displayed remarkable differential enrichment between high and low risk OSCC patients. CONCLUSIONS An immune score-based risk signature constructed presently may be useful to decide appropriate treatment options for individual OSCC patients.

Clinical value of miR-198-5p in lung squamous cell carcinoma assessed using microarray and RT-qPCR.

BACKGROUND: To examine the clinical value of miR-198-5p in lung squamous cell carcinoma (LUSC). METHODS: Gene Expression Omnibus (GEO) microarray datasets were used to explore the miR-198-5p expression and its diagnostic value in LUSC. Real-time reverse transcription quantitative polymerase chain reaction was used to evaluate the expression of miR-198-5p in 23 formalin-fixed, paraffin-embedded (FFPE) LUSC tissues and corresponding non-cancerous tissues. The correlation between miR-198-5p expression and clinic pathological features was assessed. Meanwhile, putative target messenger RNAs of miR-198-5p were identified based on the analysis of differentially expressed genes in the Cancer Genome Atlas (TCGA) and 12 miRNA prediction tools. Subsequently, the putative target genes were sent to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. RESULTS: MiR-198-5p was low expressed in LUSC tissues. The combined standard mean difference (SMD) values of miR-198-5p expression based on GEO datasets were - 0.30 (95% confidence interval (CI) - 0.54, - 0.06) and - 0.39 (95% CI - 0.83, 0.05) using fixed effect model and random effect model, respectively. The sensitivity and specificity were not sufficiently high, as the area under the curve (AUC) was 0.7749 (Q* = 0.7143) based on summarized receiver operating characteristic (SROC) curves constructed using GEO datasets. Based on the in-house RT-qPCR, miR-198-5p expression was 4.3826 ± 1.7660 in LUSC tissues and 4.4522 ± 1.8263 in adjacent normal tissues (P = 0.885). The expression of miR-198-5p was significantly higher in patients with early TNM stages (I-II) than that in cases with advanced TNM stages (III-IV) (5.4400 ± 1.5277 vs 3.5690 ± 1.5228, P = 0.008). Continuous variable-based meta-analysis of GEO and PCR data displayed the SMD values of - 0.26 (95% CI - 0.48, - 0.04) and - 0.34 (95% CI - 0.71, 0.04) based on fixed and random effect models, respectively. As for the diagnostic value of miR-198-5p, the AUC based on the SROC curve using GEO and PCR data was 0.7351 (Q* = 0.6812). In total, 542 genes were identified as the targets of miR-198-5p. The most enriched Gene Ontology terms were epidermis development among biological processes, cell junction among cellular components, and protein dimerization activity among molecule functions. The pathway of non-small cell lung cancer was the most significant pathway identified using Kyoto Encyclopedia of Genes and Genomes analysis. CONCLUSION: The expression of miR-198-5p is related to the TNM stage. Thus, miR-198-5p might play an important role via its target genes in LUSC.

Clinical Value and Prospective Pathway Signaling of MicroRNA-375 in Lung Adenocarcinoma: A Study Based on the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Bioinformatics Analysis.

BACKGROUND Lung adenocarcinoma (LUAD) is the most frequent lung cancer. MicroRNAs (miRNAs) are believed to have fundamental roles in tumorigenesis of LUAD. Although miRNAs are broadly recognized in LUAD, the role of microRNA-375 in LUAD is still not fully elucidated. MATERIAL AND METHODS We evaluated the significance of miR-375 expression in LUAD by using analysis of a public dataset from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database and a literature review. Furthermore, we investigated the biological function of miR-375 by gene ontology enrichment and target prediction analysis. RESULTS MiR-375 expression was significantly higher in LUAD by TCGA data compared to normal lung tissue (p<0.0001). In addition, a common pattern of upregulation for miR-375 in LUAD was found in our review of the literature. A total of 682 genes, both LUAD-related and miR-375-related, were obtained from the analytical integration. Critical pathways were unveiled in the network analysis of the overlaps, such as pentose and glucuronate interconversions, ascorbate and aldarate metabolism, and starch and sucrose metabolism. Furthermore, we identified covert miR-375 associated genes that might participate in LUAD by network analysis, such as FGF2 (fibroblast growth factor 2), PAX6 (paired box 6), and RHOJ. The expression of these three genes were all downregulated in LUAD. Finally, FGF2 was revealed to be negatively correlated with miR-375 in LUAD (r=-0.1821, p=0.0001). CONCLUSIONS Overall, our study provides evidence that miR-375 is essential for the progression of LUAD.

Comprehensive analysis of the long noncoding RNA HOXA11-AS gene interaction regulatory network in NSCLC cells.

BACKGROUND: Long noncoding RNAs (lncRNAs) are related to different biological processes in non-small cell lung cancer (NSCLC). However, the possible molecular mechanisms underlying the effects of the long noncoding RNA HOXA11-AS (HOXA11 antisense RNA) in NSCLC are unknown. METHODS: HOXA11-AS was knocked down in the NSCLC A549 cell line and a high throughput microarray assay was applied to detect changes in the gene profiles of the A549 cells. Bioinformatics analyses (gene ontology (GO), pathway, Kyoto Encyclopedia of Genes and Genomes (KEGG), and network analyses) were performed to investigate the potential pathways and networks of the differentially expressed genes. The molecular signatures database (MSigDB) was used to display the expression profiles of these differentially expressed genes. Furthermore, the relationships between the HOXA11-AS, de-regulated genes and clinical NSCLC parameters were verified by using NSCLC patient information from The Cancer Genome Atlas (TCGA) database. In addition, the relationship between HOXA11-AS expression and clinical diagnostic value was analyzed by receiver operating characteristic (ROC) curve. RESULTS: Among the differentially expressed genes, 277 and 80 genes were upregulated and downregulated in NSCLC, respectively (fold change ≥2.0, P < 0.05 and false discovery rate (FDR) < 0.05). According to the degree of the fold change, six upregulated and three downregulated genes were selected for further investigation. Only four genes (RSPO3, ADAMTS8, DMBT1, and DOCK8) were reported to be related with the development or progression of NSCLC based on a PubMed search. Among all possible pathways, three pathways (the PI3K-Akt, TGF-beta and Hippo signaling pathways) were the most likely to be involved in NSCLC development and progression. Furthermore, we found that HOXA11-AS was highly expressed in both lung adenocarcinoma and squamous cell carcinoma based on TCGA database. The ROC curve showed that the area under curve (AUC) of HOXA11-AS was 0.727 (95% CI 0.663-0.790) for lung adenocarcinoma and 0.933 (95% CI 0.906-0.960) for squamous cell carcinoma patients. Additionally, the original data from TCGA verified that ADAMTS8, DMBT1 and DOCK8 were downregulated in both lung adenocarcinoma and squamous cell carcinoma, whereas RSPO3 expression was upregulated in lung adenocarcinoma and downregulated in lung squamous cell carcinoma. For the other five genes (STMN2, SPINK6, TUSC3, LOC100128054, and C8orf22), we found that STMN2, TUSC3 and C8orf22 were upregulated in squamous cell carcinoma and that STMN2 and USC3 were upregulated in lung adenocarcinoma. Furthermore, we compared the correlation between HOXA11-AS and de-regulated genes in NSCLC based on TCGA. The results showed that the HOXA11-AS expression was negatively correlated with DOCK8 in squamous cell carcinoma (r = -0.124, P = 0.048) and lung adenocarcinoma (r = -0.176, P = 0.005). In addition, RSPO3, ADAMTS8 and DOCK8 were related to overall survival and disease-free survival (all P < 0.05) of lung adenocarcinoma patients in TCGA. CONCLUSIONS: Our results showed that the gene profiles were significantly changed after HOXA11-AS knock-down in NSCLC cells. We speculated that HOXA11-AS may play an important role in NSCLC development and progression by regulating the expression of various pathways and genes, especially DOCK8 and TGF-beta pathway. However, the exact mechanism should be verified by functional experiments.

How has the field of metastatic breast cancer in bones evolved over the past 22 years?

Background: Although knowledge on metastatic breast cancer in bones (MBCB) has increased rapidly over the past 22 years, a comprehensive and objective bibliometric analysis is still lacking. Materials and methods: We used R, VOSviewer, and Citespace software to conduct a bibliometric analysis of 5,497 papers on MBCB from the Web of Science Core Collection (WOSCC) using author, institution, country/region, citation, and keyword indicators. Results: A general strong sense of scholarly collaboration was noted in the MBCB field at the author, research institution, and country/region levels. We discovered some outstanding authors and highly productive institutions, but with less collaboration with other academic groups. Unbalanced and uncoordinated developments were observed among countries/regions in the field of MBCB research. We also found that by using various indicators and applying different analysis methods to them, we were able to broadly identify primary clinical practices, relevant clinical experiments, and directions for bioinformatics regarding MBCB, changes over the past 22 years, and current challenges in the field. The development of knowledge on MBCB is progressing greatly; however, MBCB is still incurable. Conclusion: This study is the first to use bibliometrics to provide an overall analysis of the scientific output of MBCB studies. Palliative therapies for MBCB are mostly in a mature state. However, research on the molecular mechanisms and immune response to tumors related to the development of treatments to cure MBCB remains relatively immature. Therefore, further research should be undertaken in this area.

WDHD1 is over-expressed in nasopharyngeal carcinoma and may control the expression of ITGAV.

Nasopharyngeal carcinoma (NPC) is a highly metastatic and invasive malignant tumor that originates in the nasopharynx. The DNA-binding protein WD repeat and HMG-box DNA-binding protein 1 (WDHD1) are highly expressed in a variety of tumours, but its expression and mechanism of action in NPC have not been reported to date. To investigate the involvement of WDHD1 in NPC, we first mined databases for the gene expression profile of NPC. Immunohistochemistry (IHC) was performed on 338 cases of NPC and 112 non-NPC samples to verify the results. We report that the expression of WDHD1 is significantly elevated in NPC. ChIP-seq was used to show that integrin alpha V (ITGAV) and WDHD1 exhibit a significant binding peak in the promoter region of the ITGAV gene. The expression levels of ITGAV and WDHD1 exhibit a significant positive correlation, and IHC was performed to show that ITGAV is highly expressed in NPC. Expression of ITGAV increased after overexpression of WDHD1, suggesting that ITGAV may be a potential target gene of WDHD1. Pathway analysis showed that both genes were closely related to the cell cycle, and flow cytometry was used to further confirm that decreased expression of WDHD1 significantly increased the number of apoptotic cells. In conclusion, our results suggest that expression of WDHD1 is increased in NPC and is likely to be associated with the NPC cell cycle; thus, we propose that WDHD1 may have the potential as a target gene for primary screening and treatment of NPC.

Clinicopathological and prognostic significance of XPO1 in solid tumors: meta-analysis and TCGA analysis.

INTRODUCTION: Exportin 1 (XPO1) is overexpressed in several solid tumors, and is associated with poor prognosis. Here, we aimed to evaluate the implication of XPO1 expression in solid tumors through a meta-analysis. METHODS: PubMed, Web of Science, and Embase databases were searched for articles published until February 2023. Statistical data of the patients, odds ratios and hazard ratios (HRs), together with their corresponding 95% confidence intervals (CIs) were pooled to assess clinicopathological features and survival outcomes. Besides, the Cancer Genome Atlas (TCGA) was used to explore the prognostic significance of XPO1 in solid tumors. RESULTS: A total of 22 works, comprising 2595 patients were included in this study. The results suggested that increased XPO1 expression was associated with a higher tumor grade, more lymph node metastasis, advanced tumor stage, and progressively worse total clinical stage. Additionally, high XPO1 expression was associated with worse overall survival (OS) (HR = 1.43, 95% CI = 1.12-1.81, P = 0.004) and shorter progression-free survival (HR = 1.40, 95% CI = 1.07-1.84, P = 0.01). An analysis using the TCGA dataset showed that high XPO1 expression was associated with poor OS and disease-free survival. CONCLUSIONS: XPO1 is a promising prognostic biomarker and may constitute a therapeutic target for solid tumors.PROSPERO registration number: CRD42023399159.

Decreased expression of transcription factor Homeobox A11 and its potential target genes in bladder cancer.

Bladder cancer (BC) ranks as the ninth most commonly diagnosed cancer worldwide. The presence of a transcription factor (TF) has been uncovered as a significant contributor to the pathophysiological changes of cancers. In present study, we elucidated the expression and clinical significance of Homeobox A11 (HOXA11) in BC for the first time, and originally investigated HOXA11 as a TF. Employing in-house immunohistochemistry (IHC), we incorporated 137 BC and 34 non-BC cases to detect the expression of HOXA11 protein in BC tissues. HOXA11-related RNA-sequencing (RNA-seq) expression and RNA microarrays were collected from public databases, the "sva" and "limma" R packages were implemented to integrate and normalize the RNA-seq data and microarrays separately. Integration expression was carried out to further evaluate the HOXA11 expression by utilizing the standard mean difference (SMD). The expression level of HOXA11 in various BC cell lines was also evaluated. We further systematically analyzed the downstream target genes of HOXA11 in BC by utilizing Chromatin Immunoprecipitation Sequencing (ChIP-seq) profiles, differentially expressed genes (DEGs), and HOXA11-related genes. Modification of histone marks on the promoter region of target genes were also discovered by histone ChIP-seq data. Results of the IHC and RNA-seq revealed the protein and mRNA expression of HOXA11 was significantly decreased in BC tissues compared to non-BC tissues (2.98 ± 1.48 vs. 8.23 ± 2.64; 6.87 ± 1.54 vs. 8.38 ± 1.42). Five platforms significantly revealed the down-regulation of HOXA11 expression in BC (GPL96, GPL570, GPL6102, GPL6884, and GPL13497). A similar decreased trend was discovered in BC tissues in expression integration with the incorporated SMD reaching -0.843 (-1.362 ~ -0.325, p = 0.001) and -1.051 (-1.674 ~ -0.428, p = 0.001). Expression of HOXA11 was down-regulated in most of the BC cell lines. COL1A1 was considered as a final HOXA11 target gene and positively related to HOXA11 with the correlation coefficient as 0.584 (95% CI: 0.371-0.739, p < 0.001). HOXA11 regulates COL1A1 expression in BC via H3K27ac modification. The expression of COL1A1 was down-regulated with the SMD reached -0.312 (p < 0.001). In conclusion, HOXA11 expression is markedly decreased and might promote the transcription of COL1A1 to inhibit BC.

Potential Molecular Mechanism of Upregulated Aryl Hydrocarbon Receptor Nuclear Translocator 2 in Nasopharyngeal Carcinoma.

Background: Currently, the benefits of nasopharyngeal carcinoma (NPC) therapy are limited, and it is necessary to further explore possible therapeutic targets. Aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) has been extensively studied in other cancer species, but little has been explored in NPC. The aim of this study was to verify the expression level of ARNT2 and its underlying mechanism in NPC. Methods: Datasets containing ARNT2 mRNA expression levels were retrieved and collected from various databases to explore the expression status of ARNT2 in NPC. ARNT2-related coexpressed genes, differential expressed genes, and target genes were obtained for functional enrichment analysis. The potential target gene of ARNT2 and their regulatory relationship were studied through ChIP-seq data. CIBERSORTx was used to assess the immune infiltration of NPC, and the association with ARNT2 expression was calculated through correlation analysis. Results: ARNT2 was upregulated and possessed an excellent discriminatory capability in NPC samples. ARNT2 positively correlated target genes were clustered in pathways in cancer, while negatively correlated target genes were enriched in immune-related pathway. The ChIP-seq information of ARNT2 and histone showed that prostaglandin-endoperoxide synthase 2 (PTGS2) was a potential target gene of ARNT2. CIBERSORTx revealed the immunity status in NPC, and ARNT2 expression was correlated with infiltration of five immune cells. Conclusions: ARNT2 is overexpressed in NPC and may regulate PTGS2 to participate in the cancer process. ARNT2 serves as a key oncogenic target in NPC patients.

Laryngeal Squamous Cell Carcinoma: Clinical Significance and Potential Mechanism of Cell Division Cycle 45.

Background: Cell division cycle 45 (CDC45) plays an important role in the occurrence and development of numerous carcinomas, but its effect in laryngeal squamous cell carcinoma (LSCC) remains unclear. Materials and Methods: The messenger RNA and protein expression levels of CDC45 in LSCC were evaluated with a t test and the standard mean difference (SMD). The ability of CDC45 expression to distinguish the LSCC was assessed through receiver operating characteristic (ROC) curves. Gene set enrichment analysis (GSEA), protein-protein interaction, public databases, and online tools were used to explore the potential molecular mechanism of CDC45 in LSCC. Results: A high expression of CDC45 was identified in LSCC (SMD = 2.61, 95% confidence interval [1.62-3.61]). Through ROC curves, the expression of CDC45 makes it feasible to distinguish the LSCC group from the non-LSCC counterpart. CDC45 was relevant to the progression-free interval of LSCC patients (log-rank p = 0.03). GSEAs show that CDC45 is related to the cell cycle. CDC45, CDC6, KIF2C, and AURKB were identified as hub genes of LSCC. E2F1 may be the regulatory transcription factor of CDC45. Conclusions: High expression of CDC45 likely demonstrates carcinogenic effects in LSCC, and CDC45 is a potential target in screening and treatment of LSCC.

CCNB1 promotes the development of hepatocellular carcinoma by mediating DNA replication in the cell cycle.

In our studies, cyclin B1 (CCNB1) mRNA and protein were overexpressed in hepatocellular carcinoma (HCC) tissues compared with non-HCC tissues. Moreover, CCNB1 was overexpressed in the serum of HCC patients. The expression of CCNB1 was associated with several crucial clinicopathologic characteristics, and the HCC patients with overexpressed CCNB1 had worse overall survival outcomes. In the screening of interactional genes, a total of 266 upregulated co-expression genes, which were positively associated with CCNB1, were selected from the datasets, and 67 downregulated co-expression genes, which were negatively associated with CCNB1, were identified. The key genes might be functionally enriched in DNA replication and the cell cycle pathways. CDC20, CCNA2, PLK1, and FTCD were selected for further research because they were highly connected in the protein-protein interaction networks. Upregulated CDC20, CCNA2, and PLK1 and downregulated FTCD might result in undesirable overall survival outcomes for HCC patients. The univariate Cox analysis results showed that CDC20 and PLK1 might be two independent risk factors, while FTCD might be protective in HCC. Therefore, CCNB1 may participate in the cell cycle of HCC by regulating DNA replication, and CCNB1 may provide a direction for the diagnosis of early-stage HCC and targeted HCC therapy.

Clinicopathological significance and underlying molecular mechanism of downregulation of basonuclin 1 expression in ovarian carcinoma.

In this study, we aim to identify the clinical significance of basonuclin 1 (BNC1) expression in ovarian carcinoma (OV) and to explore its latent mechanisms. Via integrating in-house tissue microarrays, gene chips, and RNA-sequencing data, we explored the expression and clinical value of BNC1 in OV. Immunohistochemical staining was utilized to confirm the protein expression status of BNC1. A combined SMD of -2.339 (95% CI: -3.649 to -1.028, P < 0.001) identified that BNC1 was downregulated based on 1346 samples, and the sROC (AUC = 0.93) showed a favorable discriminatory ability of BNC1 in OV patients. We used univariate and multivariate Cox regulation to evaluate the prognostic role of BNC1 for OV patients, and a combined hazard ratio of 0.717 (95% CI: 0.445-0.989, P < 0.001) revealed that BNC1 was a protective factor for OV. Furthermore, the fraction of infiltrating naive B cells, memory B cells, and other immune cells showed statistical differences between the high- and low-BNC1 expression groups through cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm. Enrichment analysis showed that BNC1 may have a relationship with immune-related items in OV. By predicting the potential regulatory transcription factors (TFs) of BNC1, friend leukemia virus integration 1 (FLI1) may be a potential upstream TF of BNC1. Corporately, a decreasing trend of BNC1 may serve as a tumor suppressor and prognostic biomarker in OV patients. Moreover, BNC1 may take part in immune-related pathways and influence the fraction of tumor-infiltrating immune cells.

Downregulated Dual-Specificity Protein Phosphatase 1 in Ovarian Carcinoma: A Comprehensive Study With Multiple Methods.

Introduction: We aimed to explore the abnormal expression of dual-specificity protein phosphatase 1 (DUSP1) and its latent molecular mechanisms in ovarian carcinoma (OVCA). Materials and Methods: Two clinical cohorts collected from two different hospitals were used to evaluate the expression of DUSP1 protein in OVCA tissues. RNA-sequencing and microarray datasets were utilised to verify DUSP1 expression at mRNA levels in both OVCA tissues and in the peripheral blood of OVCA patients. Furthermore, an integrated calculation was performed to pool the standard mean difference (SMD) from each cohort in order to comprehensively assess the expression of DUSP1 in OVCA. Furthermore, we examined the relationship among DUSP1, tumour microenvironment (TME), and chemotherapy resistance in OVCA. Moreover, we used pathway enrichment analysis to explore the underlying mechanisms of DUSP1 in OVCA. Results: A pooled SMD of -1.19 (95% CI [-2.00, -0.38], p = 0.004) with 1,240 samples revealed that DUSP1 was downregulated in OVCA at both mRNA and protein levels. The area under the receiver operating characteristic curve of 0.9235 indicated the downregulated DUSP1 in peripheral blood may have a non-invasive diagnostic value in OVCA. Through six algorithms, we identified that DUSP1 may related to tumour-infiltrating T cells and cancer associated fibroblasts (CAFs) in OVCA. Pathway enrichment demonstrated that DUSP1 might participate in the mitogen-activated protein kinase (MAPK) signalling pathway. Furthermore, DUSP1 may have relations with chemotherapy resistance, and a favourable combining affinity was observed in the paclitaxel-DUSP1 docking model. Conclusion: DUSP1 was downregulated in OVCA, and this decreasing trend may affect the infiltration of CAFs. Finally, DUSP1 may have a targeting relation with paclitaxel and participate in MAPK signaling pathways.

Downregulation of the enhancer of zeste homolog 1 transcriptional factor predicts poor prognosis of triple-negative breast cancer patients.

Background: Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer and lacks effective biomarkers. This study seeks to unravel the expression status and the prospective transcriptional mechanisms of EZH1/EZH2 in TNBC tissue samples. Moreover, another objective of this study is to reveal the prognostic molecular signatures for risk stratification in TNBC patients. Methods: To determine the expression status of EZH1/EZH2 in TNBC tissue samples, microarray analysis and immunohistochemistry were performed on in house breast cancer tissue samples. External mRNA expression matrices were used to verify its expression patterns. Furthermore, the prospective transcriptional mechanisms of EZH1/EZH2 in TNBC were explored by performing differential expression analysis, co-expression analysis, and chromatin immunoprecipitation sequencing analysis. Kaplan-Meier survival analysis and univariate Cox regression analysis were utilized to detect the prognostic molecular signatures in TNBC patients. Nomogram and time-dependent receiver operating characteristic curves were plotted to predict the risk stratification ability of the prognostic-signatures-based Cox model. Results: In-house TMAs (66 TNBC vs. 106 non-TNBC) and external gene microarrays, as well as RNA-seq datasets (1,135 TNBC vs. 6,198 non-TNBC) results, confirmed the downregulation of EZH1 at both the protein and mRNA levels (SMD = -0.59 [-0.80, -0.37]), as is opposite to that of EZH2 (SMD = 0.74 [0.40, 1.08]). The upregulated transcriptional target genes of EZH1 were significantly aggregated in the cell cycle pathway, where CCNA2, CCNB1, MAD2L1, and PKMYT1 were determined as key transcriptional targets. Additionally, the downregulated transcriptional targets of EZH2 were enriched in response to the hormone, where ESR1 was identified as the hub gene. The six-signature-based prognostic model produced an impressive performance in this study, with a training AUC of 0.753, 0.981, and 0.977 at 3-, 5-, and 10-year survival probability, respectively. Conclusion: EZH1 downregulation may be a key modulator in the progression of TNBC through negative transcriptional regulation by targeting CCNA2, CCNB1, MAD2L1, and PKMYT1.

The clinical significance of transcription factor WD repeat and HMG-box DNA binding protein 1 in laryngeal squamous cell carcinoma and its potential molecular mechanism.

BACKGROUND: Currently, high expression of WD repeat and HMG-box DNA binding protein 1 (WDHD1) has been found in a variety of tumors; but there is no research has been conducted concerning the expression of WDHD1 in laryngeal squamous cell carcinoma (LSCC). Our purpose is to investigate the expression and the latent mechanism of WDHD1 in LSCC. METHODS: Firstly, 9 data sets from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and ArrayExpress were statistically analyzed to explore the expression of WDHD1 in LSCC; immunohistochemistry was performed in 79 LSCC tissues and 44 non-cancer tissues to further verify the result. In addition, the target gene of WDHD1 was predicted and immunohistochemistry was used to detect the expression of the target gene. The potential mechanism of WDHD1 in LSCC was investigated by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and protein-protein interaction network (PPI). RESULTS: The WDHD1 mRNA was expressed at higher levels in the LSCC tissue than in the normal tissue (SMD=1.90, 95% CI=1.50-2.30); and the results of immunohistochemistry were consistent with the conclusion. Using chip-seq analysis, we found that S-phase kinase-associated protein 2 (Skp2) had a significant binding peak with WDHD1, and the expression of these two genes was significantly positively correlated. Immunohistochemistry showed that Skp2 was also highly expressed in LSCC. In addition, GO and KEGG analysis revealed the WDHD1 positively correlated genes was closely related to cell cycle, and PPI analysis identified 10 hub genes: COL7A1, COL4A2, COL4A1, COL4A6, COL11A1, COL5A2, COL1A1, COL13A1, COL8A1 and COL10A1, which may be critical to the progression of LSCC. CONCLUSIONS: WDHD1 was overexpressed in LSCC tissues. Meanwhile, WDHD1 and its target gene Skp2 for transcriptional regulation may play a role in the progression of LSCC by regulating the cell cycle.

A Comprehensive Evaluation of miR-144-3p Expression and Its Targets in Laryngeal Squamous Cell Carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is an aggressive type of head and neck squamous cell carcinoma (HNSCC) with a relatively high rate of morbidity and mortality. An altered miR-144-3p level in LSCC with a small number of patients has been previously reported. However, the clinical implication of miR-144-3p and its involved mechanism underlying this disease is not clearly elucidated. In this work, we aimed to confirm the expression of miR-144-3p with larger samples and also to identify target genes for the investigation of the underlying mechanism of miR-144-3p in LSCC. The levels of miR-144-3p were downregulated in 155 samples of LSCC tissues as compared to 26 non-LSCC samples (SMD: -0.78; 95% confidence interval (CI): -1.23, -0.32). The AUC of 0.90 in the summarized ROC curve also indicated a potential ability to differentiate LSCC from non-LSCC tissues, with a sensitivity of 0.78 and a specificity of 0.88. With respect to the molecular mechanism, we predicted the potential targets from online-based prediction, peer-reviewed publications, and RNA-seq and microarray data. In particular, the genes influenced by transfection with miR-144-3p in the LSCC FaDu cell line were collected from the microarray GSE56243. Lastly, 12 novel targets for miR-144-3p in LSCC were obtained by different algorithms. In conclusion, our study confirmed the loss or downregulation of miR-144-3p in LSCC, which might contribute to the LSCC tumorigenesis and progression via regulation of the 12 novel targets, such as IL24, ITGA6, and CEP55. In the future, further investigations are required to validate the present results.

The underlying molecular mechanism and identification of transcription factor markers for laryngeal squamous cell carcinoma.

The screening and treatment of laryngeal squamous cell carcinoma (LSCC) still perplexes clinicians, making it necessary to explore new markers. To this end, this research examined the underlying molecular mechanism of LSCC based on high-throughput datasets (n = 249) from multiple databases. It also identified transcription factors (TFs) independently associated with LSCC prognosis. Through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, differential expression genes of LSCC were deemed relevant to the extracellular matrix and its related structures or pathways, suggesting that the extracellular matrix plays an important role in LSCC. At the same time, several hub genes that may also have important roles in LSCC were identified via protein-protein interaction analysis, including CDC45, TPX2, AURKA, KIF2C, NUF, MUC1, MUC7, MUC4, MUC15, and MUC21. Eight unreported LSCC prognostic TFs - BCAT1, CHD4, FOXA2, GATA6, HNF1A, HOXB13, MAFF, and TCF4 - were screened via Kaplan-Meier curves. Cox analysis determined for the first time that HOXB13 expression and gender were independently associated with LSCC prognosis. Compared to control tissues, elevated expression of HOXB13 was found in LSCC tissues (standardized mean difference = 0.44, 95% confidence interval [0.13-0.76]). HOXB13 expression also makes it feasible to screen LSCC from non-LSCC (area under the curve = 0.77), and HOXB13 may play an essential role in LSCC by regulating HOXB7. In conclusion, HOXB13 may be a novel marker for LSCC clinical screening and treatment.