ABSTRACT
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.
Subject(s)
Bone Neoplasms , Osteosarcoma , Sarcoma, Ewing , Humans , Immunotherapy , Bone Neoplasms/therapy , BibliometricsABSTRACT
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.
ABSTRACT
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.
