Role of Up-Regulated Transmembrane Channel-Like Protein 5 in Pancreatic Adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is a malignant tumor responsible for a heavy disease burden. Previously, only one pan-cancer study of Transmembrane channel-like protein 5 (TMC5) showed that TMC5 was highly expressed in PAAD, but the results lacked comprehensive verification, and the mechanism of TMC5 in PAAD was still unclear. METHODS: For exploring the expression and clinical value of TMC5 in PAAD better, we adopted a comprehensive evaluation method, using internal immunohistochemistry (IHC) data combined with microarray and RNA-sequencing data collected from public databases. The single cell RNA-sequencing (scRNA-seq) data were exploited to explore the TMC5 expression in cell populations and intercellular communication. The potential mechanism of TMC5 in PAAD was analyzed from the aspects of immune infiltration, transcriptional regulation, function and pathway enrichment. RESULTS: Our IHC data includes 148 PAAD samples and 19 non-PAAD samples, along with the available microarray and RNA-sequencing data (1166 PAAD samples, 704 non-PAAD samples). The comprehensive evaluation results showed that TMC5 was evidently up-regulated in PAAD (SMD = 1.17). Further analysis showed that TMC5 was over-expressed in cancerous epithelial cells. Furthermore, TMC5 was up-regulated in more advanced tumor T and N stages. Interestingly, we found that STAT3 as an immune marker of Th17 cells was not only positively correlated with TMC5 and up-regulated in PAAD tissues, but also the major predicted TMC5 transcription regulator. Moreover, STAT3 was involved in cancer pathway of PAAD. CONCLUSION: Up-regulated TMC5 indicates advanced tumor stage in PAAD patients, and its role in promoting PAAD development may be regulated by STAT3.

The expression characteristics and clinical significance of ACP6, a potential target of nitidine chloride, in hepatocellular carcinoma.

BACKGROUND: Acid phosphatase type 6 (ACP6) is a mitochondrial lipid phosphate phosphatase that played a role in regulating lipid metabolism and there is still blank in the clinico-pathological significance and functional roles of ACP6 in human cancers. No investigations have been conducted on ACP6 in hepatocellular carcinoma (HCC) up to date. METHODS: Herein, we appraised the clinico-pathological significance of ACP6 in HCC via organizing expression profiles from globally multi-center microarrays and RNA-seq datasets. The molecular basis of ACP6 in HCC was explored through multidimensional analysis. We also carried out in vitro and in vivo experiment on nude mice to investigate the effect of knocking down ACP6 expression on biological functions of HCC cells, and to evaluate the expression variance of ACP6 in xenograft of HCC tissues before and after the treatment of NC. RESULTS: ACP6 displayed significant overexpression in HCC samples (standard mean difference (SMD) = 0.69, 95% confidence interval (CI) = 0.56-0.83) and up-regulated ACP6 performed well in screening HCC samples from non-cancer liver samples. ACP6 expression was also remarkably correlated with clinical progression and worse overall survival of HCC patients. There were close links between ACP6 expression and immune cells including B cells, CD8 + T cells and naive CD4 + T cells. Co-expressed genes of ACP6 mainly participated in pathways including cytokine-cytokine receptor interaction, glucocorticoid receptor pathway and NABA proteoglycans. The proliferation and migration rate of HCC cells transfected with ACP6 siRNA was significantly suppressed compared with those transfected with negative control siRNA. ACP6 expression was significantly inhibited by nitidine chloride (NC) in xenograft HCC tissues. CONCLUSIONS: ACP6 expression may serve as novel clinical biomarker indicating the clinical development of HCC and ACP6 might be potential target of anti-cancer effect by NC in HCC.

Downregulated miR-150-5p in the Tissue of Nasopharyngeal Carcinoma.

The clinical significance and potential targets of miR-150-5p have not been elucidated in nasopharyngeal carcinoma (NPC). The pooled analysis based on 539 NPC samples and 75 non-NPC nasopharyngeal samples demonstrated that the expression of miR-150-5p was down-regulated in NPC, with the area under the curve being 0.89 and the standardized mean difference being -0.66. Subsequently, we further screened the differentially expressed genes (DEGs) of 14 datasets, including 312 NPC samples and 70 non-NPC nasopharyngeal samples. After the DEGs were narrowed down with the predicted targets from the miRWalk database, 1316 prospective target genes of miR-150-5p were identified. The enrichment analysis suggested that "pathways in cancer" was the most significant pathway. Finally, six hub genes of "pathways in cancer", including EGFR, TP53, HRAS, CCND1, CDH1, and FGF2, were screened out through the STRING database. In conclusion, the down-regulation of miR-150-5p modulates the tumorigenesis and progression of NPC.

Expression Landscape and Functional Roles of HOXA4 and HOXA5 in Lung Adenocarcinoma.

BACKGROUND: The role of HOXA family genes in the occurrence and progression of a variety of human cancers has been scatteredly reported. However, there is no systematic study on the differential expression, prognostic significance and potential molecular mechanism of HOXA4 and HOXA5 in LUAD. METHODS: In-house immunohistochemistry (IHC), multi-center microarrays, RT-qPCR and RNA-seq data were incorporated for comprehensively evaluating the expression and prognostic value of HOXA4 and HOXA5 in LUAD. The mechanism of HOXA4 and HOXA5 in the formation and development of LUAD was analyzed from multiple aspects of immune correlations, upstream transcriptional regulation, functional states of single cells and co-expressed gene network. The functional roles of HOXA4 and HOXA5 in LUAD were validated by in vitro experiments. RESULTS: As a result, in 3201 LUAD samples and 2494 non-cancer lung samples, HOXA4 and HOXA5 were significantly downexpressed (P < 0.05). The aberrant expression of HOXA5 was significantly correlated with the clinical progression of LUAD (P < 0.05). HOXA5 showed remarkable prognostic value for LUAD patients (P < 0.05). The expression of HOXA4 and HOXA5 in LUAD were negatively correlated with tumor purity and positively correlated with the infiltration of various immune cells such as B cells, T cells and macrophages. HOXA4 and HOXA5 overexpression had notable inhibitory effect on the proliferation, migration and invasion of LUAD cells. CONCLUSIONS: In conclusion, the identified downexpressed HOXA4 and HOXA5 had significant distinguishing ability for LUAD samples and affected the cellular functions of LUAD cells. The low expression of HOXA5 indicated worse overall survival of LUAD patients. Therefore, the two HOXA family genes especially HOXA5 may serve as potential biomarkers for LUAD.

Downregulation of zinc finger protein 71 in laryngeal squamous cell carcinoma tissues and its potential molecular mechanism and clinical significance: a study based on immunohistochemistry staining and data mining.

BACKGROUND: The molecular mechanism of laryngeal squamous cell carcinoma (LSCC) is not completely clear, which leads to poor prognosis and treatment difficulties for LSCC patients. To date, no study has reported the exact expression level of zinc finger protein 71 (ZNF71) and its molecular mechanism in LSCC. METHODS: In-house immunohistochemistry (IHC) staining (33 LSCC samples and 29 non-LSCC samples) was utilized in analyzing the protein expression level of ZNF71 in LSCC. Gene chips and high-throughput sequencing data collected from multiple public resources (313 LSCC samples and 192 non-LSCC samples) were utilized in analyzing the exact mRNA expression level of ZNF71 in LSCC. Single-cell RNA sequencing (scRNA-seq) data was used to explore the expression status of ZNF71 in different LSCC subpopulations. Enrichment analysis of ZNF71, its positively and differentially co-expressed genes (PDCEGs), and its downstream target genes was employed to detect the potential molecular mechanism of ZNF71 in LSCC. Moreover, we conducted correlation analysis between ZNF71 expression and immune infiltration. RESULTS: ZNF71 was downregulated at the protein level (area under the curve [AUC] = 0.93, p < 0.0001) and the mRNA level (AUC = 0.71, p = 0.023) in LSCC tissues. Patients with nodal metastasis had lower protein expression level of ZNF71 than patients without nodal metastasis (p < 0.05), and male LSCC patients had lower mRNA expression level of ZNF71 than female LSCC patients (p < 0.01). ZNF71 was absent in different LSCC subpopulations, including cancer cells, plasma cells, and tumor-infiltrated immune cells, based on scRNA-seq analysis. Enrichment analysis showed that ZNF71 and its PDCEGs may influence the progression of LSCC by regulating downstream target genes of ZNF71. These downstream target genes of ZNF71 were mainly enriched in tight junctions. Moreover, downregulation of ZNF71 may influence the development and even therapy of LSCC by reducing immune infiltration. CONCLUSION: Downregulation of ZNF71 may promote the progression of LSCC by reducing tight junctions and immune infiltration; this requires further study.

Effect of phenolic compounds and hydroxyl content on the physicochemical properties of pine nut oil Pickering emulsions.

BACKGROUND: For decades, pine nut oil Pickering emulsions have been stabilized using a covalent composite of two phenolic chemicals (tannic acid, TA; and gallic acid, GA) and whey protein isolate (WPI) following alkali treatment. Based on covalent composite particles being excellent sources of high-quality stabilizers, this research explored the influence of phenolic addition and hydroxyl content on stability, rheological parameters and characterization of Pickering emulsions. RESULTS: Tannic acid was more effective in reducing the average particle size of the emulsion, which decreased from 479.4 ± 2.1 nm without addition to between 187.6 ± 5.9 and 368.2 ± 16.8 nm (P < 0.05). The potential values of all the emulsions were between -30 and -50 mV (except for the gallic acid addition of 2.5 g kg-1 ). When the phenolic addition was 7.5 g kg-1 , emulsions demonstrated the best emulsification ability. Pickering emulsion stabilized by WPI-TA and WPI-GA particles were successfully generated, according to confocal laser scanning microscopy. Rheological results showed that the increase of phenolic addition contributed to larger elastic modulus (G'), viscosity modulus (G″) and viscosity of emulsions, which was beneficial to the stability of emulsions. CONCLUSION: Both phenolic compounds significantly improved the physicochemical stability of the emulsions (P < 0.05) and their oxidative stability. Covalently crosslinking phenolic compounds to proteins is a better method to prepare stable emulsions. It is more prominent that TA shows a more significant improvement in emulsion stability due to the number of hydroxyl groups it can provide. This research might serve as a theoretical foundation for enhancing the quality of pine nut oil-related products. © 2022 Society of Chemical Industry.

[Effect and mechanism of vascular endothelial growth factor-A on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension].

OBJECTIVE: To study the role of vascular endothelial growth factor-A (VEGF-A) in pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension (HPH) by regulating survivin (SVV). METHODS: A total of 96 neonatal rats were randomly divided into three groups: HPH+VEGF-A group, HPH group, and control group. Each group was further randomly divided into 3-, 7-, 10-, and 14-day subgroups (n=8 in each subgroup). The neonatal rats in the HPH+VEGF-A and HPH groups were intratracheally transfected with adenoviral vectors with or without VEGF-A gene respectively. Those in the control group were given intratracheal injection of normal saline and were then fed under normoxic conditions. The direct measurement method was used to measure mean right ventricular systolic pressure (RVSP). Hematoxylin-eosin staining was used to observe the morphological changes of pulmonary vessels under a light microscope and calculate the percentage of media wall thickness (MT%) and the percentage of media wall cross-sectional area (MA%) in the pulmonary arterioles. Immunohistochemistry was used to measure the expression levels of VEGF-A and SVV in lung tissue. RESULTS: The HPH group had a significantly higher mean RVSP than the control and HPH+VEGF-A groups at each time point (P < 0.05). Pulmonary vascular remodeling occurred in the HPH group on day 7 of hypoxia, while it occurred in the HPH+VEGF-A group on day 10 of hypoxia. On day 7 of hypoxia, the HPH group had significantly higher MT% and MA% than the control and HPH+VEGF-A groups (P < 0.05). On days 10 and 14 of hypoxia, the HPH and HPH+VEGF-A groups had significantly higher MT% and MA% than the control group (P < 0.05). The HPH and HPH+VEGF-A groups had significantly higher expression of VEGF-A than the control group at each time point (P < 0.05). On days 3 and 7 of hypoxia, the HPH+VEGF-A group had significantly higher expression of VEGF-A than the HPH group (P < 0.05). On day 14 of hypoxia, the HPH group had significantly higher expression of SVV than the control group (P < 0.05). The HPH+VEGF-A group had significantly higher expression of SVV than the control group at each time point (P < 0.05). On days 3 and 7 of hypoxia, the HPH+VEGF-A group had significantly higher expression of SVV than the HPH group (P < 0.05). CONCLUSIONS: Prophylactic intratracheal administration of exogenous VEGF-A in neonatal rats with HPH can inhibit pulmonary vascular remodeling and reduce pulmonary arterial pressure by upregulating the expression of SVV in the early stage of hypoxia. This provides a basis for the interventional treatment of pulmonary vascular remodeling in neonatal HPH.

RNA-Sequencing, Connectivity Mapping, and Molecular Docking to Investigate Ligand-Protein Binding for Potential Drug Candidates for the Treatment of Wilms Tumor.

BACKGROUND Wilms tumor, or nephroblastoma, is a malignant pediatric embryonal renal tumor that has a poor prognosis. This study aimed to use bioinformatics data, RNA-sequencing, connectivity mapping, molecular docking, and ligand-protein binding to identify potential targets for drug therapy in Wilms tumor. MATERIAL AND METHODS Wilms tumor and non-tumor samples were obtained from high throughput gene expression databases, and differentially expressed genes (DEGs) were analyzed using the voom method in the limma package. The overlapping DEGs were obtained from the intersecting drug target genes using the Connectivity Map (CMap) database, and systemsDock was used for molecular docking. Gene databases were searched for gene expression profiles for complementary analysis, analysis of clinical significance, and prognosis analysis to refine the study. RESULTS From 177 cases of Wilms tumor, there were 648 upregulated genes and 342 down-regulated genes. Gene Ontology (GO) enrichment analysis showed that the identified DEGs that affected the cell cycle. After obtaining 21 candidate drugs, there were seven overlapping genes with 75 drug target genes and DEGs. Molecular docking results showed that relatively high scores were obtained when retinoic acid and the cyclin-dependent kinase inhibitor, alsterpaullone, were docked to the overlapping genes. There were significant standardized mean differences for three overlapping genes, CDK2, MAP4K4, and CRABP2. However, four upregulated overlapping genes, CDK2, MAP4K4, CRABP2, and SIRT1 had no prognostic significance. CONCLUSIONS RNA-sequencing, connectivity mapping, and molecular docking to investigate ligand-protein binding identified retinoic acid and alsterpaullone as potential drug candidates for the treatment of Wilms tumor.

Identification of ZIC2 as a Potential Biomarker Linked with the Clinical Progression and Immune Infiltration of Oral Cancer: A Multicenter Study.

Aim: To investigate the specific expression profile, clinicopathological significance and mechanism of Zic family member 2 (ZIC2) in oral cancer were unclear. Patients and Methods. We explored the expression pattern and clinicopathological significance of ZIC2 in oral cancer through performing in-house tissue microarray and integrated analysis global RNA-seq and microarrays containing large samples. The molecular basis of ZIC2 in oral cancer was further investigated in the aspects of transcription network and immune correlations. We also performed in vitro experiments and calculated drug sensitivity of oral cancer with different ZIC2 expression levels in response to hundreds of compounds. Results: All data unanimously proved the significant overexpression of ZIC2 in oral cancer. The upregulation of ZIC2 was remarkably associated with the malignant clinical progression of oral cancer. ZIC2 was predicted to be targeted by miRNAs such as miR-3140, miR-4999, and miR-1322. The infiltration level of CD8+ T and central memory cells was positively related to the overexpression of ZIC2. Oral cancer patients with higher ZIC2 expression showed higher drug sensitivity to two compounds including AZD8186 and ERK_2240. Conclusions: We demonstrated the upregulation of ZIC2 in oral cancer and its promoting effect on the clinical advancement of oral cancer. The potential clinical value of ZIC2 in oral cancer deserves attention.

The 'whole landscape' of research on systemic sclerosis over the past 73 years.

OBJECTIVE: This study aimed to analyse existing research on systemic sclerosis (SSc) conducted over the past 73 years to develop an essential reference for a comprehensive and objective understanding of this field of inquiry. METHODS: Using the Web of Science Core Collection, PubMed, and Scopus databases as data sources for the bibliometric analysis, we searched for published literature related to SSc over the past 73 years. The Bibliometrix package was used to analyse key bibliometric indicators, such as annual publication volume, countries, journals, author contributions, and research hotspots. RESULTS: From 1970 to 2022, the number of SSc articles steadily increased, reaching its peak in 2020-2022, with approximately 1200 papers published in each of these three years. Matucci-Cerinic et al.'s team published the most articles (425). The United States (11,282), Italy (7027), and France (5226) were the most predominant contexts. The most influential scholars in the field were Denton, Leroy, Steen, and Khanna, with H-indices of 86, 84, and 83, respectively. Arthritis and Rheumatism was the most influential journal in this field (H-index 142). High-frequency keywords in the SSc field included fibrosis (738), inflammation (242), vasculopathy (145), fibroblasts (120), and autoantibodies (118) with respect to pathogenesis, and interstitial lung disease (ILD, 708), pulmonary arterial hypertension (PAH, 696), and Raynaud's phenomenon (326) with regards to clinical manifestations. CONCLUSION: In the past three years, SSc research has entered a period of rapid development, mainly driven by research institutions in Europe and the United States. The most influential journal has been Arthritis and Rheumatism, and autoimmune aspects, vasculopathy, fibrogenesis, PAH, and ILD remain the focus of current research and indicate trends in future research.

TM9SF1 promotes bladder cancer cell growth and infiltration.

BACKGROUND: Bladder cancer (BC) is the most common urological tumor. It has a high recurrence rate, displays tutor heterogeneity, and resists chemotherapy. Furthermore, the long-term survival rate of BC patients has remained unchanged for decades, which seriously affects the quality of patient survival. To improve the survival rate and prognosis of BC patients, it is necessary to explore the molecular mechanisms of BC development and progression and identify targets for treatment and intervention. Transmembrane 9 superfamily member 1 (TM9SF1), also known as MP70 and HMP70, is a member of a family of nine transmembrane superfamily proteins, which was first identified in 1997. TM9SF1 can be expressed in BC, but its biological function and mechanism in BC are not clear. AIM: To investigate the biological function and mechanism of TM9SF1 in BC. METHODS: Cells at 60%-80% confluence were transfected with lentiviral vectors for 48-72 h to achieve stable TM9SF1 overexpression or silencing in three BC cell lines (5637, T24, and UM-UC-3). The effect of TM9SF1 on the biological behavior of BC cells was then investigated through CCK8, wound-healing assay, transwell assay, and flow cytometry. RESULTS: Overexpression of TM9SF1 increased the in vitro proliferation, migration, and invasion of BC cells by promoting the entry of BC cells into the G2/M phase. Silencing of TM9SF1 inhibited in vitro proliferation, migration, and invasion of BC cells and blocked BC cells in the G1 phase. CONCLUSION: TM9SF1 may be an oncogene in BC.

Historical context, process, and development trends of pediatric thyroid cancer research: a bibliometric analysis.

Objective: At present, the structure of knowledge in the field of childhood thyroid cancer is not clear enough, and scholars lack a sufficient understanding of the developing trends in this field, which has led to a shortage of forward-looking outputs. The purpose of this research is to help scholars construct a complete knowledge framework and identify current challenges, opportunities, and development trends. Methods: We searched the literature in the Web of Science Core Collection database on August 7, 2023 and extracted key information from the top 100 most cited articles, such as the countries, institutions, authors, themes, and keywords. We used bibliometric tools such as bibliometrix, VOSviewer, and CiteSpace for a visualization analysis and Excel for statistical descriptions. Results: The top 100 most cited articles fluctuated over time, and the research was concentrated in European countries, the United States, and Japan, among which scientific research institutions and scholars from the United States made outstanding contributions. Keyword analysis revealed that research has shifted from simple treatment methods for pediatric thyroid cancer (total thyroidectomy) and inducing factors (the Chernobyl power station accident) to the clinical applications of genetic mutations (such as the BRAF and RET genes) and larger-scale genetic changes (mutation studies of the DICER1 gene). The thematic strategy analysis showed an increasing trend towards the popularity of fusion oncogenes, while the popularity of research on traditional treatments and diagnostics has gradually declined. Conclusion: Extensive research has been conducted on the basic problems of pediatric thyroid cancer, and there has been significant outputs in the follow-up and cohort analysis of conventional diagnostic and treatment methods. However, these methods still have certain limitations. Therefore, scholars should focus on exploring fusion genes, the clinical applications of molecular targets, and novel treatment methods. This study provides a strong reference for scholars in this field.

Explosion of research on psychopathology and social media use after COVID-19: A scientometric study.

BACKGROUND: Despite advances in research on psychopathology and social media use, no comprehensive review has examined published papers on this type of research and considered how it was affected by the coronavirus disease 2019 (COVID-19) outbreak. AIM: To explore the status of research on psychopathology and social media use before and after the COVID-19 outbreak. METHODS: We used Bibliometrix (an R software package) to conduct a scientometric analysis of 4588 relevant studies drawn from the Web of Science Core Collection, PubMed, and Scopus databases. RESULTS: Such research output was scarce before COVID-19, but exploded after the pandemic with the publication of a number of high-impact articles. Key authors and institutions, located primarily in developed countries, maintained their core positions, largely uninfluenced by COVID-19; however, research production and collaboration in developing countries increased significantly after COVID-19. Through the analysis of keywords, we identified commonly used methods in this field, together with specific populations, psychopathological conditions, and clinical treatments. Researchers have devoted increasing attention to gender differences in psychopathological states and linked COVID-19 strongly to depression, with depression detection becoming a new trend. Developments in research on psychopathology and social media use are unbalanced and uncoordinated across countries/regions, and more in-depth clinical studies should be conducted in the future. CONCLUSION: After COVID-19, there was an increased level of concern about mental health issues and a changing emphasis on social media use and the impact of public health emergencies.

Identification of immune-related genes and patient selection for hepatocellular carcinoma immunotherapy.

Background: Hepatocellular carcinoma (HCC) is a malignant disease with a poor prognosis. Among the treatment strategies for HCC, tumor immunotherapy (TIT) is a promising research hotspot, in which identifying novel immune-related biomarkers and selecting suitable patient population are urgent issues to be solved. Methods: In this study, an abnormal expression map of HCC cell genes was constructed using public high-throughput data from 7,384 samples (3,941 HCC vs. 3,443 non-HCC tissues). Through single-cell RNA sequencing (scRNA-seq) cell trajectory analysis, the genes defined as potential drivers of HCC cell differentiation and development were selected. By screening for both immune-related genes and those associated with high differentiation potential in HCC cell development, a series of target genes were identified. Coexpression analysis was performed using Multiscale Embedded Gene Co-expression Network Analysis (MEGENA) to find the specific candidate genes involved in similar biological processes. Subsequently, nonnegative matrix factorization (NMF) was conducted to select patients suitable for HCC immunotherapy based on the coexpression network of candidate genes. Results: HSP90AA1, CDK4, HSPA8, HSPH1, and HSPA5 were identified as promising biomarkers for prognosis prediction and immunotherapy of HCC. Through the use of our molecular classification system, which was based on a function module containing 5 candidate genes, patients with specific characteristics were found to be suitable candidates for TIT. Conclusions: These findings provide new insights into the selection of candidate biomarkers and patient populations for future HCC immunotherapy.

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.

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.

Triosephosphate isomerase 1 may be a risk predictor in laryngeal squamous cell carcinoma: a multi-centered study integrating bulk RNA, single-cell RNA, and protein immunohistochemistry.

BACKGROUND: Although great progress has been made in anti-cancer therapy, the prognosis of laryngeal squamous cell carcinoma (LSCC) patients remains unsatisfied. Quantities of studies demonstrate that glycolytic reprograming is essential for the progression of cancers, where triosephosphate isomerase 1 (TPI1) serves as a catalytic enzyme. However, the clinicopathological significance and potential biological functions of TPI1 underlying LSCC remains obscure. METHODS: We collected in-house 82 LSCC tissue specimens and 56 non-tumor tissue specimens. Tissue microarrays (TMA) and immunohistochemical (IHC) experiments were performed. External LSCC microarrays and bulk RNA sequencing data were integrated to evaluate the expression of TPI1. We used a log-rank test and the CIBERSORT algorithm to assess the prognostic value of TPI1 and its association with the LSCC microenvironment. Malignant laryngeal epithelial cells and immune-stromal cells were identified using inferCNV and CellTypist. We conducted a comprehensive analysis to elucidate the molecular functions of TPI1 in LSCC tissue and single cells using Pearson correlation analysis, high dimensional weighted gene co-expression analysis, gene set enrichment analysis, and clustered regularly interspaced short palindromic repeats (CRISPR) screen. We explored intercellular communication patterns between LSCC single cells and immune-stromal cells and predicted several therapeutic agents targeting TPI1. RESULTS: Based on the in-house TMA and IHC analysis, TPI1 protein was found to have a strong positive expression in the nucleus of LSCC cells but only weakly positive activity in the cytoplasm of normal laryngeal cells (p < 0.0001). Further confirmation of elevated TPI1 mRNA expression was obtained from external datasets, comparing 251 LSCC tissue samples to 136 non-LSCC tissue samples (standardized mean difference = 1.06). The upregulated TPI1 mRNA demonstrated a high discriminative ability between LSCC and non-LSCC tissue (area under the curve = 0.91; sensitivity = 0.87; specificity = 0.79), suggesting its potential as a predictive marker for poor prognosis (p = 0.037). Lower infiltration abundance was found for plasma cells, naïve B cells, monocytes, and neutrophils in TPI-high expression LSCC tissue. Glycolysis and cell cycle were significantly enriched pathways for both LSCC tissue and single cells, where heat shock protein family B member 1, TPI1, and enolase 1 occupied a central position. Four outgoing communication patterns and two incoming communication patterns were identified from the intercellular communication networks. TPI1 was predicted as an oncogene in LSCC, with CRISPR scores less than -1 across 71.43% of the LSCC cell lines. TPI1 was positively correlated with the half maximal inhibitory concentration of gemcitabine and cladribine. CONCLUSIONS: TPI1 is dramatically overexpressed in LSCC than in normal tissue, and the high expression of TPI1 may promote LSCC deterioration through its metabolic and non-metabolic functions. This study contributes to advancing our knowledge of LSCC pathogenesis and may have implications for the development of targeted therapies in the future.

Nitidine chloride regulates cell function of bladder cancer in vitro through downregulating Lymphocyte antigen 75.

Nitidine chloride (NC) is effective on cancer in many tumors, but its effect on bladder cancer (BC) is unknown. We conducted cell function experiments to verify the antineoplastic effect of NC on BC cell lines (5637, T24, and UM-UC-3) in vitro. Then, mRNAs of NC-treated and NC-untreated BC cells were extracted for mRNA sequencing. Differentially expressed genes (DEGs), expression analysis, and drug molecular docking were conducted to discover the target gene of NC. Finally, functional enrichment was analyzed to explore the underlying mechanisms. NC dramatically inhibited proliferation, migration, and invasion, and it induced apoptosis and arrested the S and G2/M phases of BC cell lines. Lymphocyte antigen 75 (LY75) appeared to be the target of NC. LY75 was highly expressed and had the ability to distinguish BC tissue from non-cancerous tissue. Then, drug molecular docking confirmed the targeting relationship between NC and LY75. Gene enrichment analysis showed that the downregulated genes, after being treated with NC, were mainly enriched in pathways relevant to cell pathophysiological processes. NC inhibits BC cell proliferation, migration, and invasion, induces apoptosis, and arrests cell cycles by downregulating the expression of LY75. This study provides molecular and theoretical bases for NC treatment of BC.

Expression Profile and Molecular Basis of Cyclin-Dependent Kinases Regulatory Subunit 2 in Endometrial Carcinoma Detected by Diversified Methods.

Purpose: Our purpose was to systematically appraise the clinicopathological significance and explore the molecular bases of CKS2 in endometrial carcinoma. Patients and Methods: We measured the clinicopathological significance of CKS2 using diverse methods of public RNA-seq, microarrays, and in-house tissue microarrays to investigate the molecular basis of CKS2 in endometrial carcinoma through upstream transcriptional analysis, immune infiltration correlation analysis, and co-expression analysis. Results: Both the analysis for public RNA-seq plus the microarray data and in-house tissue microarray confirmed the significant overexpression of CKS2 in a total of 1,021 endometrial carcinoma samples compared with 279 non-cancer endometrium samples (SMD = 2.10, 95% CI = 0.72-3.48). The upregulated CKS2 was significantly related to the lymph node metastasis and advanced clinical grade of endometrial carcinoma patients (p < 0.001). Mutation types such as amplification and mRNA occurred with high frequency in the CKS2 gene in endometrial carcinoma patients. A series of miRNAs and transcription factors, such as hsa-miR-26a, hsa-miR-130a, hsa-miR-30, E2F4, MAX, and GABPA, were predicted to regulate the transcription and expression of CKS2. Significant links were found between CKS2 expression and the infiltration level of B cells, CD4+ T cells, and neutrophils in endometrial carcinoma. CKS2-coexpressed genes were actively involved in pathways such as the mitotic cell cycle process, PID aurora B pathway, and prolactin signaling pathway. Conclusion: The overexpressed CKS2 showed positive correlations with the clinical progression of endometrial carcinoma and was associated with various cancer-related biological processes and pathways, showing potential as a promising clinical biomarker for endometrial carcinoma.

Downregulation of MicroRNA-1 and Its Potential Molecular Mechanism in Nasopharyngeal Cancer: An Investigation Combined with In Silico and In-House Immunohistochemistry Validation.

BACKGROUND: This study was aimed at elucidating the molecular biological mechanisms of microRNA-1 (miR-1) in nasopharyngeal carcinoma (NPC). METHOD: In this study, we performed a pooled analysis of miR-1 expression data derived from public databases, such as GEO, ArrayExpress, TCGA, and GTEx. The miRWalk 2.0 database, combined with the mRNA microarray datasets, was used to screen the target genes, and the genes were then subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis using the DAVID 6.8 database. We then used the STRING 11.0 database and Cytoscape 3.80 software to construct a protein-protein interaction (PPI) network for screening hub genes. Immunohistochemistry (IHC) was further used to validate the expression of hub genes. Finally, potential therapeutic agents for NPC were screened by the Connectivity Map (cMap) database. RESULTS: Pooled analysis showed that miR-1 expression was significantly decreased in NPC (SMD = -0.57; P < 0.05). The summary receiver operating characteristic curve suggested that miR-1 had a good ability to distinguish cancerous tissues from noncancerous tissues (AUC = 0.78). The results of GO analysis focused on mitotic nuclear division, DNA replication, cell division, cell adhesion, extracellular space, kinesin complex, and extracellular matrix (ECM) structural constituent. The KEGG analysis suggested that the target genes played a role in key signaling pathways, such as cell cycle, focal adhesion, cytokine-cytokine receptor interaction, ECM-receptor interaction, and PI3K/Akt signaling pathway. The PPI network suggested that cyclin-dependent kinase 1 (CDK1) was the hub gene, and the CDK1 protein was subsequently confirmed to be significantly upregulated in NPC tissues by IHC. Finally, potential therapeutic drugs, such as masitinib, were obtained by the cMap database. CONCLUSION: miR-1 may play a vital part in NPC tumorigenesis and progression by regulating focal adhesion kinase to participate in cell mitosis, regulating ECM degradation, and affecting the PI3K/Akt signaling pathway. miR-1 has the potential to be a therapeutic target for NPC.