Visual analysis of bone malignancies immunotherapy: A bibliometric analysis from 2010 to 2023.

BACKGROUND: Bone malignancies (BM), including osteosarcoma, Ewing's sarcoma, chondrosarcoma, and chordoma, are characterized by high rates of recurrence and mortality, despite the availability of diverse treatment approaches. Immunotherapy has gained increasing importance in cancer treatment. However, there is a lack of comprehensive studies that utilize bibliometric analysis to explore immunotherapy for BM. METHODS: A literature search of English studies on BM and immunotherapy from 2010 to 2023 was conducted in the Web of Science Core Collection database. Bibliometric analysis tools such as VOSviewer, CiteSpace, and R Studio were utilized to examine global trends and research hotspots in this field. RESULTS: A total of 719 eligible articles, including 528 original research articles and 191 reviews, were analyzed. The number of publications has shown an increasing trend over the past 14 years, particularly in the last 5 years. The majority of the published articles on this topic originated from China (284 articles), followed by the United States and Japan. The institution with the highest number of publications and citations was the University of Texas MD Anderson Cancer Center (30 articles; 1638 citations). Dean A. Lee (12 articles) and Richard Gorlick (576 citations) were the authors with the highest contribution in terms of article count and citation count, respectively. Among these journals, Frontiers in Oncology had the highest number of articles (39 articles), while the Journal of Clinical Oncology had the highest number of citations (1878 citations). Additionally, there has been a shift in the keywords from "antitumor activity" and "NK cells" to popular topics such as "PD-L1," "open label," and "single arm." CONCLUSION: A better understanding of the current status and prospects of immunotherapy for BM is crucial for the rationale selection of appropriate BM patients for immunotherapy. This study is expected to help clinical physicians and researchers gain comprehensive insights into the developmental trends of BM immunotherapy, providing practical guidance for the application of immunotherapy in BM patients.

KYNU as a Biomarker of Tumor-Associated Macrophages and Correlates with Immunosuppressive Microenvironment and Poor Prognosis in Gastric Cancer.

Background: Kynureninase (KYNU) is a potential prognostic marker for various tumor types. However, no reports on the biological effects and prognostic value of KYNU in gastric cancer (GC) exist. Methods: GC-associated single-cell RNA sequencing and bulk RNA sequencing (bulk-seq) data were obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases, respectively. The differential expression of KYNU between GC and normal gastric tissues was first analyzed based on the bulk-seq data, followed by an exploration of the relationship between KYNU and various clinicopathological features. The Kaplan-Meier survival and Cox regression analyses were performed to determine the prognostic value of KYNU. The relationship between KYNU expression and immune cell infiltration and immune checkpoints was also explored. The biological function of KYNU was further examined at the single-cell level, and in vitro experiments were performed to examine the effect of KYNU on GC cell proliferation and invasion. Results: KYNU expression was significantly elevated in GC samples. Clinical features and survival analysis indicated that high KYNU expression was associated with poor clinical phenotypes and prognosis, whereas Cox analysis showed that KYNU was an independent risk factor for patients with GC. Notably, high expression of KYNU induced a poor immune microenvironment and contributed to the upregulation of immune checkpoints. KYNU-overexpressing macrophages drove GC progression through unique ligand-receptor pairs and transcription factors and were associated with adverse clinical phenotypes in GC. KYNU was overexpressed in GC cells in vitro, and KYNU knockout significantly inhibited GC cell proliferation and invasion. Conclusion: High KYNU expression promotes an adverse immune microenvironment and low survival rates in GC. KYNU and KYNU-related macrophages may serve as novel molecular targets in the treatment of GC.

Integrated analysis of single-cell and bulk RNA-sequencing reveals the poor prognostic value of ABCA1 in gastric adenocarcinoma.

PURPOSE: ATP-binding cassette A1 (ABCA1) is a potential prognostic marker for various tumor types. However, the biological effects and prognostic value of ABCA1 in gastric adenocarcinoma (GAC) remain unknown. METHODS: GAC-associated single-cell RNA and bulk RNA-sequencing (bulk-seq) data were obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases, respectively. The differential expression of ABCA1 between GAC and normal gastric tissues was analyzed based on the bulk-seq data. Additionally, the relationship between ABCA1 expression and various clinicopathological features was explored. Furthermore, Kaplan-Meier survival and Cox regression analyses were performed to establish the prognostic value of ABCA1. The relationships between ABCA1 expression and anti-tumor drug sensitivity and immune checkpoints were also explored. Finally, the biological functions of ABCA1 were evaluated at the single-cell level, and in vitro studies were performed to assess the effects of ABCA1 on GAC cell proliferation and invasion. RESULTS: ABCA1 expression is significantly elevated in GAC samples compared with that in normal gastric tissues. Clinical features and survival analysis revealed that high ABCA1 expression is associated with poor clinical phenotypes and prognosis, whereas Cox analysis identified ABCA1 as an independent risk factor for patients with GAC. Furthermore, high ABCA1 expression suppresses sensitivity to various chemotherapeutic drugs, including cisplatin and mitomycin, while upregulating immune checkpoints. ABCA1-overexpressing macrophages are associated with adverse clinical phenotypes in GAC and express unique ligand-receptor pairs that drive GAC progression. In vitro, ABCA1-knockdown GAC cells exhibit significantly inhibited proliferative and invasive properties. CONCLUSION: High ABCA1 expression promotes an adverse immune microenvironment and low survival rates in patients with GAC. Furthermore, ABCA1 and ABCA1-producing macrophages may serve as novel molecular targets in GAC treatment.

Integrated analysis of single-cell and bulk RNA-sequencing data reveals the prognostic value and molecular function of THSD7A in gastric cancer.

The biological role and prognostic value of thrombospondin domain-containing 7A (THSD7A) in gastric cancer remain unclear. Our purpose was to determine the molecular mechanisms underlying the functioning of THSD7A and its prognostic value in gastric cancer. Gastric cancer-associated single cell and bulk RNA sequencing data obtained from two databases, were analyzed. We used bulk RNA sequencing to examine the differential expression of THSD7A in gastric cancer and normal gastric tissues and explored the relationship between THSD7A expression and clinicopathological characteristics. Kaplan-Meier survival and Cox analyses revealed the prognostic value of THSD7A. Gene set enrichment and immune infiltration analyses were used to determine the cancer-promoting mechanisms of THSD7A and its effect on the immune microenvironment. We explored the relationship between THSD7A expression and sensitivity of anti-tumor drugs and immune checkpoint levels. Biological functions of THSD7A were validated at single-cell and in vitro levels. THSD7A expression was significantly increased in gastric cancer samples. High THSD7A expression was associated with poor clinical phenotypes and prognoses. Cox analysis showed that THSD7A was an independent risk factor for patients with gastric cancer. Enrichment analysis suggested that epithelial-mesenchymal transition and inflammatory responses may be potential pro-cancer mechanisms of THSD7A. Upregulation of THSD7A promoted infiltration by M2 macrophages and regulatory T cells. High THSD7A expression suppressed the sensitivity of patients with gastric cancer to drugs, such as 5-fluorouracil, bleomycin, and cisplatin, and upregulated immune checkpoints, such as HAVCR2, PDCD1LG2, TIGIT, and CTLA4. At the single cell level, THSD7A was an endothelial cell-associated gene and endothelial cells overexpressing THSD7A showed unique pro-oncogenic effects. In vitro experiments confirmed that THSD7A was overexpressed in gastric cancer samples and cells, and that knocking out THSD7A significantly inhibited gastric cancer cell proliferation and invasion. THSD7A overexpression may be a unique prognostic marker and therapeutic target in gastric cancer. Therefore, our study provides a new perspective on the precise treatment of gastric cancer.

ELOVL6 is associated with immunosuppression in lung adenocarcinoma through bioinformatics analysis.

The aim of this paper was to reveal the correlation between the expression of ELOVL fatty acid elongase 6 (ELOVL6) gene in lung adenocarcinoma (LUAD) and its clinical significance, immune cell infiltration level and prognosis. Expression profile data of ELOVL6 mRNA were collected from the cancer genome atlas database to analyze the differences in ELOVL6 mRNA expression in LUAD tissues and normal lung tissues, and to analyze the correlation between ELOVL6 and information on clinicopathological features. Based on TIMER database, TISDIB database and GEPIA2 database, the correlation between ELOVL6 expression and tumor immune cell infiltration in LUAD was analyzed. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses of ELOVL6-related co-expressed genes were performed to identify the involved signaling pathways and to construct their co-expressed gene protein interaction networks. Drugs affected by ELOVL6 expression were screened based on the Cell Miner database. These findings suggest that ELOVL6 plays an important role in the course of LUAD, and the expression level of this gene has a close relationship with clinicopathological characteristics and survival prognosis, and has the potential to become a prognostic marker and therapeutic target for LUAD.

Identification and validation of biomarkers for epithelial-mesenchymal transition-related cells to estimate the prognosis and immune microenvironment in primary gastric cancer by the integrated analysis of single-cell and bulk RNA sequencing data.

BACKGROUND: The epithelial-mesenchymal transition (EMT) is associated with gastric cancer (GC) progression and immune microenvironment. To better understand the heterogeneity underlying EMT, we integrated single-cell RNA-sequencing (scRNA-seq) data and bulk sequencing data from GC patients to evaluate the prognostic utility of biomarkers for EMT-related cells (ERCs), namely, cancer-associated fibroblasts (CAFs) and epithelial cells (ECs). METHODS: scRNA-seq data from primary GC tumor samples were obtained from the Gene Expression Omnibus (GEO) database to identify ERC marker genes. Bulk GC datasets from the Cancer Genome Atlas (TCGA) and GEO were used as training and validation sets, respectively. Differentially expressed markers were identified from the TCGA database. Univariate Cox, least-absolute shrinkage, and selection operator regression analyses were performed to identify EMT-related cell-prognostic genes (ERCPGs). Kaplan-Meier, Cox regression, and receiver-operating characteristic (ROC) curve analyses were adopted to evaluate the prognostic utility of the ERCPG signature. An ERCPG-based nomogram was constructed by integrating independent prognostic factors. Finally, we evaluated the correlations between the ERCPG signature and immune-cell infiltration and verified the expression of ERCPG prognostic signature genes by in vitro cellular assays. RESULTS: The ERCPG signature was comprised of seven genes (COL4A1, F2R, MMP11, CAV1, VCAN, FKBP10, and APOD). Patients were divided into high- and low-risk groups based on the ERCPG risk scores. Patients in the high-risk group showed a poor prognosis. ROC and calibration curves suggested that the ERCPG signature and nomogram had a good prognostic utility. An immune cell-infiltration analysis suggested that the abnormal expression of ERCPGs induced the formation of an unfavorable tumor immune microenvironment. In vitro cellular assays showed that ERCPGs were more abundantly expressed in GC cell lines compared to normal gastric tissue cell lines. CONCLUSIONS: We constructed and validated an ERCPG signature using scRNA-seq and bulk sequencing data from ERCs of GC patients. Our findings support the estimation of patient prognosis and tumor treatment in future clinical practice.

Integrated single-cell RNA sequencing analysis reveals a mesenchymal stem cell-associated signature for estimating prognosis and drug sensitivity in gastric cancer.

BACKGROUND: Mesenchymal stem cells (MSCs) play an important role in regulating all stages of the immune response, angiogenesis, and transformation of matrix components in the tumor microenvironment. The aim of this study was to identify the prognostic value of MSC-related signatures in patients with gastric cancer (GC). METHODS: MSC marker genes were identified by analyzing single-cell RNA sequencing (scRNA-seq) data for GC from the Gene Expression Omnibus (GEO) database. Using bulk sequencing data from the Cancer Genome Atlas-Stomach adenocarcinoma (TCGA-STAD), as a training cohort, and data from GEO, as a validation cohort, we developed a risk model consisting of MSC prognostic signature genes, and classified GC patients into high- and low-MSC risk subgroups. Multifactorial Cox regression was used to evaluate whether MSC prognostic signature was an independent prognostic factor. An MSC nomogram was constructed combining clinical information and risk grouping. Subsequently, we evaluated the effect of MSC prognostic signature on immune cell infiltration, antitumor drugs and immune checkpoints and verified the expression of MSC prognostic signature by in vitro cellular assays. RESULTS: In this study, 174 MSC marker genes were identified by analyzing scRNA-seq data. We identified seven genes (POSTN, PLOD2, ITGAV, MMP11, SDC2, MARCKS, ANXA5) to construct MSC prognostic signature. MSC prognostic signature was an independent risk factor in the TCGA and GEO cohorts. GC patients in the high-MSC risk group had worse prognoses. In addition, the MSC nomogram has a high clinical application value. Notably, the MSC signature can induce the development of a poor immune microenvironment. GC patients in the high MSC-risk group were more sensitive to anticancer drugs and tended to have higher levels of immune checkpoint markers. In qRT-PCR assays, the MSC signature was more highly expressed in GC cell lines. CONCLUSIONS: The MSC marker gene-based risk signature developed in this study can not only be used to predict the prognosis of GC patients, but also has the potential to reflect the efficacy of antitumor therapies.

Network Pharmacology and Molecular Docking Analysis on Molecular Targets and Mechanisms of Fei Jin Sheng Formula in the Treatment of Lung Cancer.

BACKGROUND: Fei Jin Sheng Formula (FJSF) is widely used in clinical treatment of lung cancer. But the underlying active ingredients and mechanisms are unclear. OBJECTIVE: To investigate the active components and functional mechanisms of FJSF in treating lung cancer using a network pharmacology approach and molecular docking combined with vitro experiments Methods: Based on the TCMSP and related literature, the chemical components of related herbs in FJSF were collected. The active components of FJSF were screened by ADME parameters, and the targets were predicted by the Swiss Target Prediction database. The "drug-active ingredient-target" network was constructed by Cytoscape. Disease-related targets of lung cancer were acquired from GeneCards, OMIM, and TTD databases. Then drug-disease intersection target genes were obtained through the Venn tool. GO analysis and KEGG pathway enrichment analysis were performed via the Metascape database. Cytoscape was used to construct a PPI network and perform topological analysis. Kaplan-Meier Plotter was used to analyze the relationship between DVL2 and the prognosis of lung cancer patients. xCell method was used to estimate the relationship between DVL2 and immune cell infiltration in lung cancer. Molecular docking was performed by AutoDockTools-1.5.6. The results were verified by experiments in vitro. RESULTS: FJSF contained 272 active ingredients and 52 potential targets for lung cancer. GO enrichment analysis is mainly related to cell migration and movement, lipid metabolism, and protein kinase activity. KEGG pathway enrichment analysis mainly involves PI3K-Akt, TNF, HIF-1, and other pathways. Molecular docking shows that the compound Xambioona, quercetin and methyl palmitate in FJSF has a strong binding ability with NTRK1, APC, and DVL2. Analysis of the data in UCSC to analyze the expression of DVL2 in lung cancer shows that DVL2 was overexpressed in lung adenocarcinoma tissues. Kaplan-Meier analysis shows that the higher DVL2 expression in lung cancer patients was associated with poorer overall survival and poorer survival in stage I patients. It was negatively correlated with the infiltration of various immune cells in the lung cancer microenvironment. Vitro Experiment showed that Methyl Palmitate (MP) can inhibit the proliferation, migration, and invasion of lung cancer cells, and its mechanism of action may be to downregulate the expression of DVL2. CONCLUSION: FJSF may play a role in inhibiting the occurrence and development of lung cancer by downregulating the expression of DVL2 in A549 cells through its active ingredient Methyl Palmitate. These results provide scientific evidence for further investigations into the role of FJSF and Methyl Palmitate in the treatment of lung cancer.

Single-Cell RNA Sequencing Reveals the Role of Epithelial Cell Marker Genes in Predicting the Prognosis of Colorectal Cancer Patients.

Single-cell RNA sequencing (scRNA-seq) is increasingly used in studies on gastrointestinal cancers. This study investigated the prognostic value of epithelial cell-associated biomarkers in colorectal cancer (CRC) using scRNA-seq data. We downloaded and analysed scRNA-seq data from four CRC samples from the Gene Expression Omnibus (GEO), and we identified marker genes of malignant epithelial cells (MECs) using CRC transcriptome and clinical data downloaded from The Cancer Genome Atlas (TCGA) and GEO as training and validation cohorts, respectively. In the TCGA training cohort, weighted gene correlation network analysis, univariate Cox proportional hazard model (Cox) analysis, and least absolute shrinkage and selection operator regression analysis were performed on the marker genes of MEC subsets to identify a signature of nine prognostic MEC-related genes (MECRGs) and calculate a risk score based on the signature. CRC patients were divided into high- and low-risk groups according to the median risk score. We found that the MECRG risk score was significantly correlated with the clinical features and overall survival of CRC patients, and that CRC patients in the high-risk group showed a significantly shorter survival time. The univariate and multivariate Cox regression analyses showed that the MECRG risk score can serve as an independent prognostic factor for CRC patients. Gene set enrichment analysis revealed that the MECRG signature genes are involved in fatty acid metabolism, p53 signalling, and other pathways. To increase the clinical application value, we constructed a MECRG nomogram by combining the MECRG risk score with other independent prognostic factors. The validity of the nomogram is based on receiver operating characteristics and calibration curves. The MECRG signature and nomogram models were well validated in the GEO dataset. In conclusion, we established an epithelial cell marker gene-based risk assessment model based on scRNA-seq analysis of CRC samples for predicting the prognosis of CRC patients.

Sodium-Based Cylindrical Plasmonic Waveguides in the Near-Infrared.

Subwavelength optical field confinement and low-loss propagation are of great significance for compact photonic integration. However, the field confinement capability of plasmonic devices is always accompanied by the inherent Ohmic loss. Although recent studies have shown that sodium (Na) exhibits lower loss than noble metals in the near-infrared band, the field confinement ability has not been adequately assessed. Meanwhile, the high chemical reactivity of Na should be regulated for practical application. Two dielectric-coated Na nanowires, consisting of cylindrical Na nanowires with one or two dielectric layers as claddings, are proposed and investigated in this paper. Based on finite element calculations, we thoroughly study the modal fields and low-loss propagation properties of dielectric-coated Na nanowires. The results demonstrate that Na exhibits lower loss and stronger field confinement than the typical plasmonic material silver. These findings indicate the performance of plasmonic devices can be considerably improved by employing the metal Na compared with devices using noble metals, which may promote the applications in subwavelength photonic devices.

Identification by Bioinformatics Analysis of Potential Key Genes Related to the Progression and Prognosis of Gastric Cancer.

Objective: Despite increasingly sophisticated medical technology, the prognosis of patients with advanced gastric cancer is still not objectively certain. Therefore, it is urgent to identify new diagnostic and prognostic biomarkers. To identify potential critical genes related to gastric cancer's staging mechanism and to the prognosis of gastric cancer. Methods: Dynamic trend analysis was conducted to find genes with similar trends in gastric cancer staging in order to explore the differentially expressed genes in gastric cancer and identify the intersection of the results of the dynamic trend analysis. Functional predictive analysis were performed on the obtained genes to observe the expression of prognostic genes in gastric cancer and in gastric cancer stages as well as the correlation with tumor immune cell infiltration. Gastric cancer samples were collected and sequenced for follow-up analysis based on the results of the Cancer Genome Atlas (TCGA) database analysis. Results: The expression of genes enriched in module 0 had a similar trend in gastric cancer staging. 3213 differential genes were screened. A total of 50 intersection genes were obtained among genes with similar trends, of which only 10 genes have prognostic significance in gastric cancer. These 10 genes were correlated with macrophage infiltration in varying degrees. In addition, we found that AGT was significantly abnormally expressed in the results of sample sequencing. AGT was related to the occurrence of gastric cancer and interacted with brd9, golph3, nom1, klhl25, and psmd11. Conclusion: AGT has prominent abnormal expression in gastric cancer and may promote gastric cancer progression. This study provides a new direction for further exploring potential biomarkers and molecular targeted gastric cancer therapy.

Serum level of miR-142-3p predicts prognostic outcome for colorectal cancer following curative resection.

OBJECTIVE: MicroRNA (miR)-142-3p may function as a tumor suppressor in the development of various cancers. In this study, we measured serum levels of miR-142-3p in patients with colorectal cancer (CRC) to evaluate the diagnostic and prognostic value of miR-142-3p. METHODS: Serum samples from 363 consecutive CRC patients and 156 healthy controls were retrospectively collected. Serum miR-142-3p levels were measured using real-time quantitative reverse transcription polymerase chain reaction. All patients were followed up regularly after tumor resection. The correlation between serum miR-142-3p level and survival outcomes was analyzed. RESULTS: Serum levels of miR-142-3p were significantly lower in CRC patients than in healthy volunteers. A low serum miR-142-3p level was significantly associated with advanced cancer. Survival analysis demonstrated that patients with a low serum miR-142-3p had a lower 5-year overall survival rate than patients with a high serum miR-142-3p level (67.4% vs. 76.9%). Serum miR-142-3p level was also shown to be an independent risk factor for CRC in multivariate analysis (hazard ratio, 2.68; 95% confidence interval: 1.21-7.95). CONCLUSIONS: Serum miR-142-3p might serve as a useful diagnostic and prognostic marker for CRC.

Downregulation of MiR-1297 predicts poor prognosis and enhances gastric cancer cell growth by targeting CREB1.

Dysregulation of mircoRNAs (miRs) that act as tumor suppressors or oncogenes is participated in tumorigenesis and progression. The aim of the study is to investigate the role and mechanism of miR-1297 in gastric cancer (GC). Here, we demonstrated that miR-1297 expression was significantly lower in GC tissue samples compared to adjacent normal tissue samples in 62 cases GC patients. Lower miR-1297 expression positively associated with larger tumor size, lymph node metastasis, advanced TNM stage and poor survival time of patients. Upregulation of miR-1297 significantly inhibited cell proliferation and cell colony forming abilities in vitro. However, downregulation of miR-1297 can cause the reverse biological function changes. In vivo, miR-1297 overexpression suppressed tumor growth. Luciferase reporter assay showed that CREB1 was a direct target of miR-1297 in GC. MiR-1297 inhibited the expression of CREB1 by targeting the 3'UTR of CREB1. Additionally, we demonstrated that CREB1 overexpression rescued the effects on GC cell growth induced by miR-1297. Therefore, these results indicated that miR-1297 might be a prognostic predictor for GC and potential target of GC treatment.

Salvianolic acid B reverses multidrug resistance in nude mice bearing human colon cancer stem cells.

Salvianolic acid B (SalB) is a water­soluble phenolic compound, extractable from Salvia miltiorrhiza, and has previously been demonstrated to reverse tumor multidrug resistance (MDR) in colon cancer cells. Cancer stem cells (CSCs) are closely associated with drug resistance. Therefore, establishing a nude mouse model bearing human colon CSCs is important for the study of the mechanisms underlying colon cancer drug resistance as well as the reversal of drug resistance. The present study aimed to establish a nude mouse model bearing human colon CSCs and to investigate the effects of SalB on the drug resistance exhibited by the nude mouse model as well as determine its underlying mechanism. Cells from two colon cancer cell lines (LoVo and HCT­116) were cultured in serum­free medium to obtain CSCs­enriched spheroid cells. Following this, nude mice were transplanted with LoVo and HCT­116 colon CSCs to establish the CSC nude mouse model, which was subsequently demonstrated to exhibit MDR. The results of the present study revealed that following treatment with SalB, the chemotherapeutic drug resistance of xenografts was reversed to a certain extent. Western blot analysis was performed to investigate the expression levels of cluster of differentiation (CD)44, CD133, transcription factor sox­2 (SOX2) and ATP­binding cassette sub­family G member 2 (ABCG2) proteins, and the results demonstrated that treatment with SalB downregulated the expression of CD44, SOX2 and ABCG2 proteins in both LoVo and HCT­116 colon CSCs xenografts. In conclusion, the results of the present study revealed that a serum­free suspension method can be performed to successfully isolate colon CSCs. In addition, a nude mice bearing colon CSCs animal model was successfully established, and associated tumors were confirmed to exhibit MDR. Furthermore, SalB was demonstrated to successfully reverse MDR in nude mice bearing LoVo and HCT­116 colon CSCs, as well as suppress the expression of CD44, SOX2 and ABCG2 proteins.